Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Mechanisms of Cardiac Pain

Robert D. Foreman, Kennon M. Garrett, Robert W. Blair

10.1002/cphy.c140032

Source: Volume 5, Issue 2, April 2015

Published online: March 2015

Full Article on Wiley Online Library



ABSTRACT

Angina pectoris is cardiac pain that typically is manifested as referred pain to the chest and upper left arm. Atypical pain to describe localization of the perception, generally experienced more by women, is referred to the back, neck, and/or jaw. This article summarizes the neurophysiological and pharmacological mechanisms for referred cardiac pain. Spinal cardiac afferent fibers mediate typical anginal pain via pathways from the spinal cord to the thalamus and ultimately cerebral cortex. Spinal neurotransmission involves substance P, glutamate, and transient receptor potential vanilloid‐1 (TRPV1) receptors; release of neurokinins such as nuclear factor kappa b (NF‐kb) in the spinal cord can modulate neurotransmission. Vagal cardiac afferent fibers likely mediate atypical anginal pain and contribute to cardiac ischemia without accompanying pain via relays through the nucleus of the solitary tract and the C1‐C2 spinal segments. The psychological state of an individual can modulate cardiac nociception via pathways involving the amygdala. Descending pathways originating from nucleus raphe magnus and the pons also can modulate cardiac nociception. Sensory input from other visceral organs can mimic cardiac pain due to convergence of this input with cardiac input onto spinothalamic tract neurons. Reduction of converging nociceptive input from the gallbladder and gastrointestinal tract can diminish cardiac pain. Much work remains to be performed to discern the interactions among complex neural pathways that ultimately produce or do not produce the sensations associated with cardiac pain. © 2015 American Physiological Society. Compr Physiol 5:929‐960, 2015.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Viscerosomatic convergence onto upper thoracic spinothalamic tract neurons. Both cardiac sensory information and somatic sensory information from the chest and upper arm converge onto the same population of spinothalamic tract neurons in the upper thoracic (T1‐T5) spinal dorsal horn segments. In this and all subsequent figures, green pathways are excitatory, and the recorded central neuron and its axon are colored blue.
Figure 2. Figure 2. Mediators that activate and/or enhance sensitivity of cardiac afferent fibers. Each of the substances can affect both spinal and vagal afferent fibers.
Figure 3. Figure 3. Effect of topical treatment with iodo‐resiniferatoxin (iodo‐RTX, 50 μmol/L) on mean response activity of cardiac afferents to 5 min of ischemia. Results indicate that iodo‐RTX significantly reduced the responses of cardiac afferents to ischemia. Data are presented as mean ± SEM. *P < 0.05 versus preischemia control; #P < 0.05 versus afferent response to initial ischemia. (Adapted, with permission, from 251.)
Figure 4. Figure 4. TNF‐α in rat dorsal root ganglia. Closed bars represent mean optical density of immunoreactive material for TNF‐α in the dorsal root ganglia of rats receiving coronary artery occlusion for 0.5, 1, 3, and 6 h. Hatched bars represent mean optical density of immunoreactive material for TNF‐α in the dorsal root ganglia of rats 0.5, 1, 3, and 6 h following sham surgery. Results indicate that the expression of TNF‐α in dorsal root ganglia was increased following coronary artery occlusion compared to sham. Data are presented as mean ± SEM. **P < 0.01 versus sham; *P < 0.05 versus sham. (Adapted, with permission, from 238.)
Figure 5. Figure 5. Comparison of the responses of mechanically sensitive and mechanically insensitive cardiac afferents to 5 min of myocardial ischemia. Results indicate that both types of cardiac afferents significantly increased their discharge rate in response to myocardial ischemia, but the responses of mechanically insensitive afferents were significantly more robust than the responses of mechanically sensitive afferents. Data are presented as mean ± SEM. *P < 0.05 compared with control, #P < 0.05 compared with the response of mechanically sensitive afferents to ischemia. (Adapted, with permission, from 250.)
Figure 6. Figure 6. Patterns of convergence of cardiac and somatic inputs onto spinothalamic tract neurons in the upper thoracic and cervical spinal segments. The T1‐T5 and C5‐C6 segments receive converging nociceptive cardiac input and somatic input from the chest and upper arm, although the cellular responses to cardiac stimuli are more intense in T1‐T5. Spinothalamic tract neurons in the C7‐C8 segments receive no appreciable cardiac input and receive somatic input from the distal arm and hand. The dashed line indicates that the pathway(s) by which cardiac input reaches C5‐C6 are not defined. All pathways in this diagram are excitatory.
Figure 7. Figure 7. Effects of intrapericardial resiniferatoxin (RTX) on upper thoracic spinal neuronal responses to bradykinin (BK) and capsaicin (CAP). Intrapericardial BK or CAP was administered approximately 20 to 30 min after pretreatment with RTX. The results show that increased activity responses to BK or CAP were markedly reduced after RTX treatment. Data are presented as mean ± SEM. *P < 0.05 compared with spontaneous activity (SA) before (−RTX) and after (+RTX) administration of RTX. (Reprinted, with permission, from 267.)
Figure 8. Figure 8. Effects of coronary artery occlusion on spinal levels of substance P. Filled bars represent the mean optical density of antisubstance P immunoreactive material in the spinal cord of rats receiving coronary artery occlusion (CAO) for 0.5, 1, 3, or 6 h. Hatched bars represent the mean optical density of antisubstance P immunoreactive material in spinal cord of rats at 0.5, 1, 3, and 6 h following sham surgery. Results indicate that the levels of substance P in the spinal cord were significantly elevated following CAO. Data are presented as mean ± SEM. *P < 0.05 compared with time‐matched sham surgery group. (Reprinted, with permission, from 132.)
Figure 9. Figure 9. Neurotransmitter interactions within the spinal dorsal horn. Nociceptive spinal cardiac afferents release both glutamate and substance P onto spinothalamic tract neurons. Glutamate stimulates NMDA and AMPA receptors, and substance P stimulates NK1R receptors. Under appropriate conditions microglial cells can release TNF‐α which can influence both the presynaptic and postsynaptic nerve terminals.
Figure 10. Figure 10. Effects of coronary artery occlusion (CAO) on TNF‐α in rat spinal cord. Bars represent mean optical density of immunoreactive material for TNF‐α in the spinal cord of rats receiving coronary artery occlusion for 0.5, 1, 3, and 6 h or sham surgery. Results indicate that TNF‐α is expressed in the spinal cord in response to CAO. Data are presented as mean ± SEM. **P < 0.01 versus sham, *P < 0.05 versus sham. (Adapted, with permission, from 238.)
Figure 11. Figure 11. Cell responses to intracardiac injection of bradykinin (BK) and effects of left thoracic vagus nerve simulation on those responses in monkeys. Background cell activity of spinothalamic tract neurons was recorded and then BK was injected into the left atrium. At the peak of the response to BK, the left thoracic vagus nerve was stimulated for 5 s and cell activity was recorded (BK + V). Cessation of stimulation the left thoracic vagus nerve caused the cell activity to return to the bradykinin‐stimulated level (second BK). Thus, left vagus nerve stimulation reduced neuronal responses to intracardiac BK. Data are presented as mean ± SEM. *P < 0.001 compared to BK. (Adapted, with, permission from 11.)
Figure 12. Figure 12. Modulation of thoracic neuronal responses by the C1‐C2 segments. Neuronal activity was recorded from neurons with unidentified projections in the T3‐T4 segments in rats. The panels show the rate of discharge of extracellular potentials from the spinal neurons. The lower panel on the right shows that the neuron responded robustly to bradykinin (10‐5 M, 0.2 mL) injected into the pericardial sac via a catheter. In the upper panel on the right, a glutamate 2.2 mm pledget (1.0 M absorbed onto filter paper) was placed on the surface of the spinal cord at the C1‐C2 segments before application of bradykinin to the heart. The response to bradykinin was substantially reduced in the presence of glutamate, suggesting that a propriospinal pathway from the upper cervical cord to the upper thoracic cord suppresses neuronal responses. The neurotransmitter(s) mediating inhibition is/are not yet known. In this and subsequent figures, pathways colored red are inhibitory.
Figure 13. Figure 13. Convergence patterns of spinal, vagal, and somatic afferents onto spinothalamic tract neurons in different spinal segments. The vagal pattern is superimposed on Figure 6. Vagal afferents transmitting cardiac nociceptive information terminate in the nucleus of the solitary tract, which then excites neurons in the C1‐C2 segments. These spinothalamic tract neurons receive somatic input from the neck region, but do not receive significant input from spinal cardiac afferents. All pathways in this diagram are excitatory.
Figure 14. Figure 14. Effects of subcoeruleus‐parabrachial stimulation on spinothalamic tract cell responses to bradykinin in monkeys. The increase in cell activity caused by bradykinin was significantly greater than control (*P < 0.05). Subcoeruleus‐parabrachial stimulation reduced cell activity below the bradykinin level (#P < 0.05). (Reprinted, with permission, from 45.)
Figure 15. Figure 15. Modulation of thoracic neuronal responses by the subcoeruleus and parabrachial regions of the pons. Stimulation of this region inhibits neuronal responses to noxious spinal cardiac input. The dashed line indicates that the specific pathway(s) mediating this effect are not defined.
Figure 16. Figure 16. Responses of T3‐T4 spinal neurons to intrapericardial injections of bradykinin (BK) in rats implanted with either corticosterone or cholesterol in the central nucleus of the amygdala. The duration of activity in response to BK was significantly longer in the corticosterone‐implanted animals compared with cholesterol‐implanted animals. Data are presented as mean ± SEM. *P < 0.05.
Figure 17. Figure 17. The number of T3‐T4 spinal neurons with short‐lasting excitatory and long‐lasting excitatory responses to intrapericardial injections of bradykinin in rats implanted with either corticosterone or cholesterol in the central nucleus of the amygdala. Neurons with excitatory responses to bradykinin were subdivided into two groups based on the time of recovery to control activity after bradykinin was removed from the pericardial sac. Activity shifted from the short‐lasting excitatory (e.g., the response lasts only as long as the stimulus is applied) to long‐lasting excitatory (e.g., the responses lasts well beyond the period the stimulus was applied) classification in corticosterone‐implanted animals.
Figure 18. Figure 18. Amygdala relay through the C1‐C2 segments. The responses of neurons in the T3‐T4 segments to stimulation of the amygdala were compared before (bottom panel on right) and after ibotenic acid was applied to either the C1‐C2 or C5‐C6 segments. Ibotenic acid placed on C5‐C6 produced no diminution of response, but abolished the response if placed on C1‐C2. Thus, the amygdala excites neurons in C1‐C2, but not in C5‐C6, that then inhibit responses of neurons in T3‐T4.
Figure 19. Figure 19. Effects of intrapericardial injection of bradykinin (BK) on neurons in the T3 segment of the rat spinal cord. Solid bars represent the spontaneous activity of neurons in rats with gastroesophageal reflux (GER) or surgical controls. Hatched bars represent the cell activity following injection of BK into the pericardial sac in rats with GER and surgical controls. Results indicate that neuronal responses to intracardiac BK were greater in rats with GER. Data are presented as mean ± SEM. *P < 0.05. (Reprinted, with permission, from 272.)
Figure 20. Figure 20. Responses of gallbladder‐responsive cells and nonresponsive cells to injection of bradykinin (BK) into the left atrium. Values represent the cell activity of cells with gallbladder input (GB input) or no gallbladder input (no GB input). BK values represent peak activity during responses. Results indicate that cells receiving GB input had more robust responses to BK than cells without GB input. *P < 0.05 compared with cells without gallbladder input. (Adapted, with, permission from 13.)
Figure 21. Figure 21. Heart gallbladder interactions. Upper panels: (left) Cardiac symptoms over 1 month in patients with coronary artery disease (CAD) and patients with coronary artery disease + gallbladder stone (CAD + Gs). Results indicate that patients were more likely to experience angina if they had a gallstone. (Right) Pressure pain thresholds (PPTs) in the left anterior chest area in healthy subjects (normal), and two groups of patients with either CAD only or CAD + Gs presenting a comparable number of angina episodes in the preceding month. Compared to normals, patients with CAD had lower PPTs, and patients with CAD and Gs experienced a greater lowering of PPT compared to CAD. Lower panels: (left) Cardiac symptoms for 1 month before (before Cholecystx) and 1 month after cholecystectomy (after Cholecystx). Removal of the stone significantly reduced the number of angina episodes. (Right) PPTs in the chest area before and after the operation in CAD + Gs patients. Removal of the stone increased the PPT. Note: The upper right CAD + Gs group is the same as the lower right before Cholecystx group; mean values are different because there was one less patient in the lower right group. Overall results suggest that the greater the number of visceral organs with pathology, the greater the likelihood of experiencing pain from any single organ. (Adapted, with permission, from 126.)
Figure 22. Figure 22. Multi‐organ convergence onto spinothalamic tract neurons. Spinothalamic tract neurons in the upper thoracic segments receive converging nociceptive inputs from the heart, esophagus, and gallbladder, along with somatic input from the chest and upper arm. The dashed line indicates that the precise pathway by which gallbladder input reaches the upper thoracic cord has not been identified.
Figure 23. Figure 23. Summary of major visceral pathways influencing spinothalamic tract neuronal activity described in this review. For description, see the concluding paragraph.


Figure 1. Viscerosomatic convergence onto upper thoracic spinothalamic tract neurons. Both cardiac sensory information and somatic sensory information from the chest and upper arm converge onto the same population of spinothalamic tract neurons in the upper thoracic (T1‐T5) spinal dorsal horn segments. In this and all subsequent figures, green pathways are excitatory, and the recorded central neuron and its axon are colored blue.


Figure 2. Mediators that activate and/or enhance sensitivity of cardiac afferent fibers. Each of the substances can affect both spinal and vagal afferent fibers.


Figure 3. Effect of topical treatment with iodo‐resiniferatoxin (iodo‐RTX, 50 μmol/L) on mean response activity of cardiac afferents to 5 min of ischemia. Results indicate that iodo‐RTX significantly reduced the responses of cardiac afferents to ischemia. Data are presented as mean ± SEM. *P < 0.05 versus preischemia control; #P < 0.05 versus afferent response to initial ischemia. (Adapted, with permission, from 251.)


Figure 4. TNF‐α in rat dorsal root ganglia. Closed bars represent mean optical density of immunoreactive material for TNF‐α in the dorsal root ganglia of rats receiving coronary artery occlusion for 0.5, 1, 3, and 6 h. Hatched bars represent mean optical density of immunoreactive material for TNF‐α in the dorsal root ganglia of rats 0.5, 1, 3, and 6 h following sham surgery. Results indicate that the expression of TNF‐α in dorsal root ganglia was increased following coronary artery occlusion compared to sham. Data are presented as mean ± SEM. **P < 0.01 versus sham; *P < 0.05 versus sham. (Adapted, with permission, from 238.)


Figure 5. Comparison of the responses of mechanically sensitive and mechanically insensitive cardiac afferents to 5 min of myocardial ischemia. Results indicate that both types of cardiac afferents significantly increased their discharge rate in response to myocardial ischemia, but the responses of mechanically insensitive afferents were significantly more robust than the responses of mechanically sensitive afferents. Data are presented as mean ± SEM. *P < 0.05 compared with control, #P < 0.05 compared with the response of mechanically sensitive afferents to ischemia. (Adapted, with permission, from 250.)


Figure 6. Patterns of convergence of cardiac and somatic inputs onto spinothalamic tract neurons in the upper thoracic and cervical spinal segments. The T1‐T5 and C5‐C6 segments receive converging nociceptive cardiac input and somatic input from the chest and upper arm, although the cellular responses to cardiac stimuli are more intense in T1‐T5. Spinothalamic tract neurons in the C7‐C8 segments receive no appreciable cardiac input and receive somatic input from the distal arm and hand. The dashed line indicates that the pathway(s) by which cardiac input reaches C5‐C6 are not defined. All pathways in this diagram are excitatory.


Figure 7. Effects of intrapericardial resiniferatoxin (RTX) on upper thoracic spinal neuronal responses to bradykinin (BK) and capsaicin (CAP). Intrapericardial BK or CAP was administered approximately 20 to 30 min after pretreatment with RTX. The results show that increased activity responses to BK or CAP were markedly reduced after RTX treatment. Data are presented as mean ± SEM. *P < 0.05 compared with spontaneous activity (SA) before (−RTX) and after (+RTX) administration of RTX. (Reprinted, with permission, from 267.)


Figure 8. Effects of coronary artery occlusion on spinal levels of substance P. Filled bars represent the mean optical density of antisubstance P immunoreactive material in the spinal cord of rats receiving coronary artery occlusion (CAO) for 0.5, 1, 3, or 6 h. Hatched bars represent the mean optical density of antisubstance P immunoreactive material in spinal cord of rats at 0.5, 1, 3, and 6 h following sham surgery. Results indicate that the levels of substance P in the spinal cord were significantly elevated following CAO. Data are presented as mean ± SEM. *P < 0.05 compared with time‐matched sham surgery group. (Reprinted, with permission, from 132.)


Figure 9. Neurotransmitter interactions within the spinal dorsal horn. Nociceptive spinal cardiac afferents release both glutamate and substance P onto spinothalamic tract neurons. Glutamate stimulates NMDA and AMPA receptors, and substance P stimulates NK1R receptors. Under appropriate conditions microglial cells can release TNF‐α which can influence both the presynaptic and postsynaptic nerve terminals.


Figure 10. Effects of coronary artery occlusion (CAO) on TNF‐α in rat spinal cord. Bars represent mean optical density of immunoreactive material for TNF‐α in the spinal cord of rats receiving coronary artery occlusion for 0.5, 1, 3, and 6 h or sham surgery. Results indicate that TNF‐α is expressed in the spinal cord in response to CAO. Data are presented as mean ± SEM. **P < 0.01 versus sham, *P < 0.05 versus sham. (Adapted, with permission, from 238.)


Figure 11. Cell responses to intracardiac injection of bradykinin (BK) and effects of left thoracic vagus nerve simulation on those responses in monkeys. Background cell activity of spinothalamic tract neurons was recorded and then BK was injected into the left atrium. At the peak of the response to BK, the left thoracic vagus nerve was stimulated for 5 s and cell activity was recorded (BK + V). Cessation of stimulation the left thoracic vagus nerve caused the cell activity to return to the bradykinin‐stimulated level (second BK). Thus, left vagus nerve stimulation reduced neuronal responses to intracardiac BK. Data are presented as mean ± SEM. *P < 0.001 compared to BK. (Adapted, with, permission from 11.)


Figure 12. Modulation of thoracic neuronal responses by the C1‐C2 segments. Neuronal activity was recorded from neurons with unidentified projections in the T3‐T4 segments in rats. The panels show the rate of discharge of extracellular potentials from the spinal neurons. The lower panel on the right shows that the neuron responded robustly to bradykinin (10‐5 M, 0.2 mL) injected into the pericardial sac via a catheter. In the upper panel on the right, a glutamate 2.2 mm pledget (1.0 M absorbed onto filter paper) was placed on the surface of the spinal cord at the C1‐C2 segments before application of bradykinin to the heart. The response to bradykinin was substantially reduced in the presence of glutamate, suggesting that a propriospinal pathway from the upper cervical cord to the upper thoracic cord suppresses neuronal responses. The neurotransmitter(s) mediating inhibition is/are not yet known. In this and subsequent figures, pathways colored red are inhibitory.


Figure 13. Convergence patterns of spinal, vagal, and somatic afferents onto spinothalamic tract neurons in different spinal segments. The vagal pattern is superimposed on Figure 6. Vagal afferents transmitting cardiac nociceptive information terminate in the nucleus of the solitary tract, which then excites neurons in the C1‐C2 segments. These spinothalamic tract neurons receive somatic input from the neck region, but do not receive significant input from spinal cardiac afferents. All pathways in this diagram are excitatory.


Figure 14. Effects of subcoeruleus‐parabrachial stimulation on spinothalamic tract cell responses to bradykinin in monkeys. The increase in cell activity caused by bradykinin was significantly greater than control (*P < 0.05). Subcoeruleus‐parabrachial stimulation reduced cell activity below the bradykinin level (#P < 0.05). (Reprinted, with permission, from 45.)


Figure 15. Modulation of thoracic neuronal responses by the subcoeruleus and parabrachial regions of the pons. Stimulation of this region inhibits neuronal responses to noxious spinal cardiac input. The dashed line indicates that the specific pathway(s) mediating this effect are not defined.


Figure 16. Responses of T3‐T4 spinal neurons to intrapericardial injections of bradykinin (BK) in rats implanted with either corticosterone or cholesterol in the central nucleus of the amygdala. The duration of activity in response to BK was significantly longer in the corticosterone‐implanted animals compared with cholesterol‐implanted animals. Data are presented as mean ± SEM. *P < 0.05.


Figure 17. The number of T3‐T4 spinal neurons with short‐lasting excitatory and long‐lasting excitatory responses to intrapericardial injections of bradykinin in rats implanted with either corticosterone or cholesterol in the central nucleus of the amygdala. Neurons with excitatory responses to bradykinin were subdivided into two groups based on the time of recovery to control activity after bradykinin was removed from the pericardial sac. Activity shifted from the short‐lasting excitatory (e.g., the response lasts only as long as the stimulus is applied) to long‐lasting excitatory (e.g., the responses lasts well beyond the period the stimulus was applied) classification in corticosterone‐implanted animals.


Figure 18. Amygdala relay through the C1‐C2 segments. The responses of neurons in the T3‐T4 segments to stimulation of the amygdala were compared before (bottom panel on right) and after ibotenic acid was applied to either the C1‐C2 or C5‐C6 segments. Ibotenic acid placed on C5‐C6 produced no diminution of response, but abolished the response if placed on C1‐C2. Thus, the amygdala excites neurons in C1‐C2, but not in C5‐C6, that then inhibit responses of neurons in T3‐T4.


Figure 19. Effects of intrapericardial injection of bradykinin (BK) on neurons in the T3 segment of the rat spinal cord. Solid bars represent the spontaneous activity of neurons in rats with gastroesophageal reflux (GER) or surgical controls. Hatched bars represent the cell activity following injection of BK into the pericardial sac in rats with GER and surgical controls. Results indicate that neuronal responses to intracardiac BK were greater in rats with GER. Data are presented as mean ± SEM. *P < 0.05. (Reprinted, with permission, from 272.)


Figure 20. Responses of gallbladder‐responsive cells and nonresponsive cells to injection of bradykinin (BK) into the left atrium. Values represent the cell activity of cells with gallbladder input (GB input) or no gallbladder input (no GB input). BK values represent peak activity during responses. Results indicate that cells receiving GB input had more robust responses to BK than cells without GB input. *P < 0.05 compared with cells without gallbladder input. (Adapted, with, permission from 13.)


Figure 21. Heart gallbladder interactions. Upper panels: (left) Cardiac symptoms over 1 month in patients with coronary artery disease (CAD) and patients with coronary artery disease + gallbladder stone (CAD + Gs). Results indicate that patients were more likely to experience angina if they had a gallstone. (Right) Pressure pain thresholds (PPTs) in the left anterior chest area in healthy subjects (normal), and two groups of patients with either CAD only or CAD + Gs presenting a comparable number of angina episodes in the preceding month. Compared to normals, patients with CAD had lower PPTs, and patients with CAD and Gs experienced a greater lowering of PPT compared to CAD. Lower panels: (left) Cardiac symptoms for 1 month before (before Cholecystx) and 1 month after cholecystectomy (after Cholecystx). Removal of the stone significantly reduced the number of angina episodes. (Right) PPTs in the chest area before and after the operation in CAD + Gs patients. Removal of the stone increased the PPT. Note: The upper right CAD + Gs group is the same as the lower right before Cholecystx group; mean values are different because there was one less patient in the lower right group. Overall results suggest that the greater the number of visceral organs with pathology, the greater the likelihood of experiencing pain from any single organ. (Adapted, with permission, from 126.)


Figure 22. Multi‐organ convergence onto spinothalamic tract neurons. Spinothalamic tract neurons in the upper thoracic segments receive converging nociceptive inputs from the heart, esophagus, and gallbladder, along with somatic input from the chest and upper arm. The dashed line indicates that the precise pathway by which gallbladder input reaches the upper thoracic cord has not been identified.


Figure 23. Summary of major visceral pathways influencing spinothalamic tract neuronal activity described in this review. For description, see the concluding paragraph.
References
 1. Abe T , Morgan D , Sengupta JN , Gebhart GF , Gutterman DD . Attenuation of ischemia‐induced activation of cardiac sympathetic afferents following brief myocardial ischemia in cats. J Auton Nerv Syst 71: 28‐36, 1998.
 2. Albe‐Fessard D , Besson JM . Convergent thalamic and cortical projections. The non‐specific system. In: Iggo A , editor. Handbook of Sensory Physiology. Berlin: Springer‐Verlag, pp. 489‐560, 1973.
 3. Albutaihi IA , Hautvast RW , DeJongste MJ , Ter Horst GJ , Staal MJ . Cardiac nociception in rats: Neuronal pathways and the influence of dermal neurostimulation on conveyance to the central nervous system. J Mol Neurosci 20: 43‐52, 2003.
 4. Al‐Chaer ED , Feng Y , Willis WD . Comparative study of viscerosomatic input onto postsynaptic dorsal column and spinothalamic tract neurons in the primate. J Neurophysiol 82: 1876‐1882, 1999.
 5. Al‐Chaer ED , Kawasaki M , Pasricha PJ . A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development. Gastroenterology 119: 1276‐1285, 2000.
 6. Al‐Chaer ED , Lawand, NB , Westlund, KN , Willis, WD . Pelvic visceral input into the nucleus gracilis is largely mediated by the postsynaptic dorsal column pathway. J Neurophysiol 76: 2675‐2690, 1996.
 7. Al‐Chaer ED , Lawand NB , Westlund KN , Willis WD . Visceral nociceptive input into the ventral posterolateral nucleus of the thalamus: A new function for the dorsal column pathway. J Neurophysiol 76: 2661‐2674, 1996.
 8. Al‐Chaer ED , Westlund KN , Willis WD . Sensitization of postsynaptic dorsal column neuronal responses by colon inflammation. NeuroReport 8: 3267‐3273, 1997.
 9. Allen GV , Saper CB , Hurley KM , Cechetto DF . Organization of visceral and limbic connections in the insular cortex of the rat. J Comp Neurol 311: 1‐16, 1991
 10. Ammons WS , Blair RW , Foreman RD . Vagal afferent inhibition of primate thoracic spinothalamic neurons. J Neurophysiol 50: 926‐940, 1983.
 11. Ammons WS , Blair RW , Foreman RD . Vagal afferent inhibition of spinothalamic cell responses to sympathetic afferents and bradykinin in the monkey. Circ Res 53: 603‐612, 1983.
 12. Ammons WS , Blair RW , Foreman RD . Greater splanchnic excitation of primate Tl‐T5 spinothalamic neurons. J Neurophysiol 51: 592‐603, 1984.
 13. Ammons WS , Blair RW , Foreman RD . Responses of primate T1‐T5 spinothalamic neurons to gallbladder distension. Am J Physiol 247: R995‐R1002, 1984.
 14. Ammons WS , Blair RW , Foreman RD . Raphe magnus inhibition of primate T1‐T4 spinothalamic cells with cardiopulmonary visceral input. Pain 20: 247‐260, 1984c.
 15. Ammons WS , Foreman RD . Cardiovascular and T2‐T4 dorsal horn cell responses to gallbladder distention in the cat. Brain Res 321: 267‐277, 1984.
 16. Ammons WS , Girardot M‐N , Foreman RD . T2‐T5 spinothalamic neurons projecting to medial thalamus with viscerosomatic input. J Neurophysiol 54: 73‐89, 1985.
 17. Ammons WS , Girardot M‐N , Foreman RD . Effects of intracardiac bradykinin on T2‐T5 medial spinothalamic cells. Am J Physiol 249: R147‐R152, 1985.
 18. Bain WA , Irving JT , McSwiney BA . The afferent fibres from the abdomenn in the splanchnic nerves. J Physiol (Lond) 84: 323‐333, 1935.
 19. Baker DG , Coleridge HM , Coleridge JCG . Vagal afferent C fibres from the ventricle. In: Hainsworth R , Kidd C , Linden RJ , editors. Cardiac Receptors. Cambridge: Cambridge University Press, pp. 117‐137, 1979.
 20. Baker DG , Coleridge HM , Coleridge JCG , Nerdrum T . Search for a cardiac nociceptor: stimulation by bradykinin of sympathetic afferent nerve endings in the heart of cat. J Physiol 306: 519‐536, 1980.
 21. Beal MC . Viscerosomatic reflexes: A review. J Am Osteopath Assoc 85: 786‐801, 1985.
 22. Beall JE , Martin RF , Applebaum AE , Willis WD . Inhibition of primate spinothalamic tract neurons by stimulation in the region of the nucleus raphe magnus. Brain Res 114: 328‐333, 1976.
 23. Becker R , Sure U , Bertalanffy H . Punctate midline myelotomy. A new approach in the management of visceral pain. Acta Neurochir (Wien) 141: 881‐883, 1999.
 24. Beckstead RM , Morse JR , Norgren R . The nucleus of the solitary tract in the monkey: Projections to the thalamus and brainstem nuclei. Comp Neurol 190: 259‐282, 1980.
 25. Beckstead RM , Norgren R . An autoradiographic examination of the central distribution of the trigeminal, facial, glossopharyngeal, and vagal nerves in the monkey. Comp Neurol 184: 455‐472, 1979.
 26. Bennett GJ . Update on the neurophysiology of pain transmission and modulation: Focus on the NMDA‐receptor. J Pain Symptom Manage 19: S2‐S6, 2000.
 27. Bennett JR , Atkinson M . The differentiation between oesophageal and cardiac pain. Lancet 2: 1123‐1127, 1966.
 28. Bentivoglio M , Macchi C , Albanese A . The cortical projections of the thalamic intralaminar nuclei as studies in cat and rat with the multiple‐fluorescence retrograde tracing technique. Neurosci Lett 26: 5‐10, 1981.
 29. Berendse HW , Groenewengen VH . Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat. Neuroscience 42: 173‐102, 1991.
 30. Berger HJ , Zaret BL , Speroff L , Cohen LS , Wolfson S . Cardiac prostaglandin release during myocardial ischemia induced by atrial pacing in patients with coronary artery disease. Am J Cardiol 39: 481‐486, 1977.
 31. Berger UV , Hediger MA . Distribution of the glutamate transporters GLAST and GLT‐1 in rat circumventricular organs, meninges, and dorsal root ganglia. J Comp Neurol 421: 385‐399, 2000.
 32. Berkley KJ , Hubscher CH . Are there separate central nervous system pathways for touch and pain? Nat Med 1: 766‐773, 1995.
 33. Besson JM , Chaouch A. Peripheral and spinal mechanisms of nociception. Physiol Rev 67: 67‐186, 1987.
 34. Blair RW , Ammons WS , Foreman RD . Responses of thoracic spinothalamic and spinoreticular cells to coronary artery occlusion. J Neurophysiol 51: 636‐648, 1984.
 35. Blair RW , Evans AR . Responses of medullary raphespinal neurons to electrical stimulation of thoracic sympathetic afferents, vagal afferents, and to other sensory inputs in cats. J Neurophysiol 66: 2084‐2094, 1991a.
 36. Blair RW , Evans AR . Responses of medullary raphespinal neurons to coronary artery occlusion, epicardial bradykinin, and cardiac mechanical stimuli in cats. J Neurophysiol 66: 2095‐2106, 1991b.
 37. Blair RW , Weber RN , Foreman RD . Characteristics of primate spinothalamic tract neurons receiving viscerosomatic convergent inputs in T3‐T5 segments. J Neurophysiol 46: 797‐811, 1981.
 38. Blair RW , Weber RN , Foreman RD . Responses of thoracic spinothalamic neurons to intracardiac injection of bradykinin in the monkey. Cir Res 51: 83‐94, 1982.
 39. Blair RW , Weber RN , Foreman RD . Responses of thoracic spinoreticular and spinothalamic cells to intracardiac bradykinin. Am J Physiol 246: H500‐H507, 1984.
 40. Blomqvist A , Ma W , Berkley KJ . Spinal input to the parabrachial nucleus in the cat. Brain Res 480: 29‐36, 1989.
 41. Boivie J . An anatomical reinvestigation of the termination of the spinothalamic tract in the monkey. J Comp Neurol 186: 343‐370, 1979.
 42. Bolser DC , Chandler MJ , Garrison DW , Foreman RD . Effects of intracardiac bradykinin and capsaicin on spinal and spinoreticular neurons. Am J Physiol 257: H1543‐H1550, 1989.
 43. Bonica JJ. Management of Pain. London: Lea & Febiger, pp. 133‐179, 1990.
 44. Bradesi S . Role of spinal cord glia in the central processing of peripheral pain perception. Neurogastroenterol Motil 22: 499‐511, 2010.
 45. Brennan TJ , Oh U‐T , Girardot M‐N , Ammons WS , Foreman RD . Inhibition of cardiopulmonary input to thoracic spinothalamic tract cells by stimulation of the subcoeruleus‐parabrachial region in the primate. J.Auton Nerv Sys 18: 61‐72, 1987.
 46. Brook RA , Wahlqvist P , Kleinman NL , Wallander MA , Campbell SM , Smeeding JE . Cost of gastro‐oesophageal reflux disease to the employer: A perspective from the United States. Aliment Pharmacol Ther 26: 889‐898, 2007.
 47. Brown AM , Malliani A . Spinal sympathetic reflexes initiated by coronary receptors. J Physiol 212: 685‐705, 1971.
 48. Burstein R . Somatosensory and visceral input to the hypothalamus limbic system. Prog Brain Res 107: 257‐267, 1996.
 49. Burton, H. , Loewy, A.D. Descending projections from the marginal cell layer and other regions of the monkey spinal cord. Brain Res 116: 485‐491, 1976.
 50. Camilleri M , Saslow SB , Bharucha AE . Gastrointestinal sensation. Mechanisms and relation to functional gastrointestinal disorders. Gastroenterol Clin North Am 25: 247‐258, 1996.
 51. Cannon RO 3rd , Epstein SE . “Microvascular angina” as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol 61: 1338‐1343, 1988.
 52. Cannon , Watson RM , Rosing DR , Epstein SE . Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol 1: 1359‐1373, 1983.
 53. Casati R , Lombardi F , Malliani A . Afferent sympathetic unmyelinated fibres with left ventricular endings in cats. J Physiol 292: 135‐148, 1979.
 54. Casey KL , Jones EG . Supraspinal mechanisms: An overview of ascending pathways: brainstem and thalamus. Neurosci Res Prog Bull 16: 103‐118, 1978.
 55. Caterina MJ , Schumacher MA , Tominaga M , Rosen TA , Levine JD , Julius D . The capsaicin receptor: A heat‐activated ion channel in the pain pathway. Nature 389: 816‐824, 1997.
 56. Cechetto DF , Saper CB . Evidence for a viscerotopic sensory representation in the cortex and thalamus in the rat. J Comp Neurol 262: 27‐45, 1987.
 57. Cechetto DF , Standaert DG , Saper CB . Spinal and trigeminal dorsal horn projections to the parabrachial nucleus in the rat. J Comp Neurol 240: 153‐160, 1985.
 58. Cervero F . Somatic and visceral inputs to the thoracic spinal cord of the cat: Effects of noxious stimulation of the biliary system. J Physiol (Lond) 337: 51‐67, 1983.
 59. Cervero F . Sensory innervation of the viscera: Peripheral basis of visceral pain. Physiol Rev 74: 95‐138, 1994.
 60. Cervero F . Visceral pain: Mechanisms of peripheral and central sensitization. Ann Med 27: 235‐239, 1995.
 61. Cervero F , Connell LA . Distribution of somatic and visceral primary afferent fibres within the thoracic spinal cord of the cat. J Comp Neurol 230: 88‐98, 1984.
 62. Cervero F , Janig W . Visceral nociceptors: A new world order. Trends Neurosci 15: 374‐378, 1992.
 63. Chandler MJ , Hobbs ST , Bolser DC , Foreman RD . Effects of vagal afferent stimulation on cervical spinothalamic tract neurons in monkeys. Pain 44: 81‐87, 1991.
 64. Chandler MJ , Zhang J , Foreman RD . Vagal, sympathetic and somatic sensory inputs to upper cervical (C1‐C3) spinothalamic tract neurons in monkeys. J Neurophysiol 76: 2555‐2567, 1996.
 65. Chandler MJ , Zhang J , Qin C , Foreman RD . Spinal inhibitory effects of cardiopulmonary afferent inputs in monkeys: Neuronal processing in high cervical segments. J Neurophysiol 87: 1290‐1302, 2002.
 66. Chandler MJ , Zhang J , Qin C , Yuan Y , Foreman RD . Intrapericardiac injections of algogenic chemicals excite primate C1‐C2 spinothalamic tract neurons. Am J Physiol Regul Integr Comp Physiol 279: R560‐R568, 2000.
 67. Chauhan A , Mullins PA , Taylor G , Petch MC , Schofield PM . Cardioesophageal reflex: A mechanism for “linked angina” in patients with angiographically proven coronary artery disease. J Am Coll Cardiol 27: 1621‐1628, 1996.
 68. Chauhan A , Petch MC , Schofield PM . Effect of oesophageal acid instillation on coronary blood flow. Lancet 341: 1309‐1310, 1993.
 69. Ciuffo AA , Ouyang P , Becker LC , Levin L , Weisfeldt ML . Reduction of sympathetic inotropic response after ischemia in dogs. Contributor to stunned myocardium. J Clin Invest 75: 1504‐1509, 1985.
 70. Cohn PF . Silent myocardial ischemia. Ann Intern Med 109: 312‐317, 1988.
 71. Cohn PF , Fox KM , Daly C . Silent myocardial ischemia. Circulation 108: 1263‐1277, 2003.
 72. Coleridge HM , Coleridge JCG . Cardiovascular afferents involved in regulation of peripheral vessels. Annu Rev Physiol 42: 413‐427, 1980.
 73. Coleridge HM , Coleridge JCG , Kidd C . Cardiac receptors in the dog with particular reference to two types of endings in the ventricular wall. Physiol (Lond) 174: 323‐339, 1964.
 74. Coleridge JCG , Hemingway A , Holmes RL , Linden RJ . The location of atrial receptors in the dog: A physiological and histological study. Physiol (Lond) 136: 174‐197, 1957.
 75. Covey WC , Ignatowski TA , Renauld AE , Knight PR , Nader ND , Spengler RN . Expression of neuron‐associated tumor necrosis factor alpha in the brain is increased during persistent pain. Reg Anesth 27: 357‐366, 2002.
 76. Crea F , Biasucci LM , Buffon A , Liuzzo G , Monaco C , Caligiuri G , Kol A , Sperti G , Cianflone D , Maseri A . Role of inflammation in the pathogenesis of unstable coronary artery disease. Am J Cardiol 80(5A): 10E‐16E, 1997.
 77. Csendes A , Sepulveda A . Intraluminal gallbladder pressure measurements in patients with chronic or acute cholecystites. Am J Surg 13: 383‐385, 1980.
 78. Cullen M L , Reese HL . Myocardial circulatory changes measured by clearance of Na24‐effect of common duct distension on myocardial circulation. J Appl Physiol 5: 281‐284, 1952.
 79. Cunha FQ , Poole S , Lorenzetti BB , Ferreira SH . The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 107: 660‐664, 1992.
 80. Dean BB , Crawley JA , Schmitt CM , Wong J , Ofman JJ. The burden of illness of gastro‐oesophageal reflux disease: Impact on work productivity. Aliment Pharmacol Ther 17: 1309‐1317, 2003.
 81. De Biasi S , Rustioni A . Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord. Proc Natl Acad Sci USA 85: 7820‐7824, 1988.
 82. Deedwania PC , Carbajal EV . Prevalence and patterns of silent myocardial ischemia during daily life in stable angina patients receiving conventional antianginal drug therapy. Am J Cardiol 65: 1090‐1096, 1990.
 83. De Leo JA , Tawfik VL , LaCroix‐Fralish ML . The tetrapartite synapse: Path to CNS sensitization and chronic pain. Pain 122: 17‐21, 2006.
 84. Dejongste MJ , Hautvast RW , Ruiters MH , Ter Horst GJ . Spinal cord stimulation and the induction of c‐fos and heat shock protein 72 in the central nervous system of rats. Neuromodulation 1: 73‐84, 1998.
 85. DeVon, HA , Zerwic, JJ . The symptoms of unstable angina: Do women and men differ? Nurs Res 52, 108‐118, 2003.
 86. Dobrzycki S , Baniukiewicz A , Korecki J , Bachorzewska‐Gajewska H , Prokopczuk P , Musial WJ , Kaminski KA , Dabrowski A . Does gastro‐esophageal reflux provoke the myocardial ischemia in patients with CAD? Int J Cardiol 104: 67‐72, 2005.
 87. Donald DE , Shepherd JT . Reflexes from the heart and lungs; Physiological curiosities or important regulatory mechanisms. Cardiavasc Res 12: 449‐469, 1978.
 88. Douglas, PS. , Ginsburg, GS . The evaluation of chest pain in women. N Engl J Med 334: 1311‐1315, 1996.
 89. Downman CBB . Skeletal muscle reflexes of splanchnic and intercostal nerve origin in acute and decerebrate cats. J Neurophysiol 18: 217‐235, 1955.
 90. Downman CBB . The distribution of splanchnic afferents in the spinal cord of the cat. J Physiol (Lond) 137: 66‐79, 1957.
 91. Drewes AM , Schipper KP , Dimcevski G , Petersen P , Andersen OK , Gregersen H , Arendt‐Nielsen L . Multimodal assessment of pain in the esophagus: A new experimental model. Am J Physiol Gastrointest Liver Physiol 283: G95‐G103, 2002.
 92. Drewes AM , Schipper KP , Dimcevski G , Petersen P , Andersen OK , Gregersen H , Arendt‐Nielsen L . Multi‐modal induction and assessment of allodynia and hyperalgesia in the human oesophagus. Eur J Pain 7: 539‐49, 2003.
 93. Droste C , Greenlee MW , Roskamm H . A defective angina pectoris pain warning system: Experimental findings of ischemic and electrical pain test. Pain 26: 199‐209, 1986.
 94. Droste C , Roskamm H . Experimental pain measurement in patients with asymptomatic myocardial ischemia. Am Coll Cardiol 1: 940‐945, 1983.
 95. Duggan AW . Release of neuropeptide in the spinal cord. In: Nyberg F , Sharma HS , Wiesenfeld‐Hallin Z , editors. Neuropeptides in the Spinal Cord Progress in Brain Research. New York: Elsevier, pp. 197‐223, 1995.
 96. Duggan AW , Hendry IA , Green LJ , Morton CR , and Zhao ZQ . Cutaneous stimuli releasing immunoreactive substance P in the dorsal horn of the cat. Brain Res 451: 261‐273, 1988.
 97. Eriksson B , Svedenhag J , Martinsson A , Sylvén C . Effect of epinephrine infusion on chest pain in syndrome X in the absence of signs of myocardial ischaemia. Am J Cardiol 75: 241‐245, 1995.
 98. Euchner‐Wamser I , Meller ST , Gebhart GF . A model of cardiac nociception in chronically instrumented rats: Behavioral and electrophysiological effects of pericardial administration of algogenic substances. Pain 58: 117‐128, 1994.
 99. Falcone C , Sconocchia R , Guasti L , Codega S , Monetrnartini C , Specchia G . Dental pain threshold and angina pectoris in patients with coronary artery disease. Am Coll Cardiol 12: 348‐352, 1988.
 100. Farrokhi F , Vaezi MF . Extra‐esophageal manifestations of gastroesophageal reflux. Oral Dis 13: 349‐359, 2007.
 101. Felder RB , Thames MD . Interaction between cardiac receptors and sinoaortic baroreceptors in the control of efferent cardiac sympathetic nerve activity during myocardial ischemia in dogs. Circ Res 45: 728‐736, 1979.
 102. Feng Y , Cui M , Al‐Chaer ED , Willis WD . Epigastric antinociception by cervical dorsal column lesions in rats. Anesthesiology 89: 411‐420, 1998.
 103. Ferreira SH . Prostaglandins, aspirin‐like drugs and analgesia. Nat New Biol 240: 200‐203, 1972.
 104. Festi D , Dormi A , Capodicasa S , Staniscia T , Attili AF , Loria P , Pazzi P , Mazzella G , Sama C , Roda E , Colecchia A . Incidence of gallstone disease in Italy: Results from a multicenter, population‐based Italian study (the MICOL project). World J Gastroenterol 14: 5282‐5289, 2008.
 105. Fields HL , Basbaum AI , Clanton CH , Anderson SD . Nucleus raphe magnus inhibition of spinal cord dorsal horn neurons. Brain Res 126: 441‐453, 1977.
 106. Flores NA , Sheridan DJ . The pathophysiological role of platelets during myocardial ischaemia. Cardiovasc Res 28: 295‐302, 1994.
 107. Foreman RD . Mechanisms of cardiac pain. Annu Rev Physiol 61: 143‐167, 1999.
 108. Foreman RD , Applebaum AE , Beall JE , Trevino DL , Willis WD . Responses of primate spinothalamic tract neurons to electrical stimulation of hindlimb peripheral nerves. J Neurophysiol 38: 132‐145, 1975.
 109. Foreman RD , Blair RW , Weber RN . Viscerosomatic convergence onto T2‐T4 spinoreticular, spinoreticular‐spinothalamic, and spinothalamic tract neurons in the cat. Exp Neurol 85: 597‐619, 1984.
 110. Foreman RD , Qin C . Neuromodulation of cardiac pain and cerebral vasculature: neural mechanisms. Cleve Clin J Med 76(Suppl 2): S75‐S79, 2009.
 111. Franco‐Cereceda A , Liska J . Potential of calcitonin gene‐related peptide in coronary heart disease. Pharmacology 60: 1‐8, 2000.
 112. Francis J , Zhang Z‐H , Weiss RM , Felder RB . Neural regulation of the proinflammatory cytokine response to acute myocardial infarction. Am J Physiol Heart Circ Physiol 287: H791‐H797, 2004.
 113. Frangogiannis N , Lindsey ML , Michael LH , Youker KA , Bressler RB , Mendoza LH , Spengler RN , Smith CW , Entman ML . Resident cardiac mast cells degranulate and release preformed TNF‐a, initiating the cytokine cascade in experimental canaine myocardial ischemia/reperfusion. Circulation 98: 699‐710, 1998.
 114. Frank L , Kleinman L , Ganoczy D , McQuaid K , Sloan S , Eggleston A , Tougas G , Farup C . Upper gastrointestinal symptoms in North America: Prevalence and relationship to healthcare utilization and quality of life. Dig Dis Sci 45: 809‐818, 2000.
 115. Frot M , Mauguiere F . Dual representation of pain in the operculoinsular cortex in humans. Brain 126: 438‐450, 2003.
 116. Fu L‐W , Longhurst JC . Interactions between histamine and bradykinin in stimulation of ischaemically sensitive cardiac afferents in felines. J Physiol (Lond) 565: 1007‐1017, 2005.
 117. Fu L‐W and Longhurst JC . Regulation of cardiac afferent excitability in ischemia. Sensory serves. In: Canning BJ , Spina D , editors. Handbook of Experimental Pharmacology. Springer‐Verlag Berlin Heidelberg, Vol. 194; pp. 185‐225, 2009.
 118. Fu L‐W , Longhurst JC . Bradykinin and thromboxane A2 reciprocally interact to synergistically stimulate cardiac spinal afferents during myocardial ischemia. Am J Physiol Heart Circ Physiol 298: H235‐H244, 2010.
 119. Garrison DW , Chandler MJ , Foreman RD . Viscerosomatic convergence onto feline spinal neurons from esophagus, heart and somatic fields: Effects of inflammation. Pain 49: 373‐382, 1992.
 120. Gaspardone A , Crea F , Tomai F , Iamele M , Crossman DC , Pappagallo M , Versaci F , Chiariello L , Gioffrè PA . Substance P potentiates the algogenic effects of intraarterial infusion of adenosine. J Am Coll Cardiol 24: 477‐482, 1994.
 121. Gebhart GF . Pathobiology of visceral pain: molecular mechanisms and therapeutic implications IV. Visceral afferent contributions to the pathobiology of visceral pain. Am J Physiol Gastrointest Liver Physiol 278: G834‐G838, 2000.
 122. Gegelashvili G , Schousboe A . High afinity glutamate transporters: Regulation of expression and activity. Mol Pharmacol 52: 6‐15, 1997.
 123. Geppetti P , Maggi CA , Perretti F , Frilli S , Manzini S . Simultaneous release by bradykinin of substance P‐and calcitonin gene‐related peptide immunoreactivities from capsaicin‐sensitive structures in guinea‐pig heart. Br J Pharmacol 94: 288‐290, 1988.
 124. Gerhart KD , Wilcox TK , Chung JM , Willis WD . Inhibition of nociceptive and nonnociceptive responses of primate spinothalamic cells by stimulation in medial brain stem. J Neurophysiol 45: 121‐136, 1981.
 125. Ghione S , Rosa C , Mezzasalma L , Panattoni E . Arterial hypertension is associated with hypalgesia in humans. Hypertension 12: 491‐497, 1988.
 126. Giamberardino MA , Costantini R , Affaitati G , Fabrizio A , Lapenna D , Tafuri E , Mezzetti A . Viscero‐visceral hyperalgesia: Characterization in different clinical models. Pain 151: 307‐322, 2010.
 127. Girardot M‐N , Brennan TJ , Ammons WS , Foreman RD . Effects of stimulating the subcoeruleus‐parabrachial region on the non‐noxious and noxious responses of T2‐T4 spinothalamic tract neurons in the primate. Brain Res 409: 19‐30, 1987.
 128. Glazier JJ , Chierchia S , Brown MJ , Maseri A . Importance of generalized defective perception of painful stimuli as a cause of silent myocardial ischemia in chronic stable angina pectoris. Am J Cardiol 58: 667‐672, 1986.
 129. Goodman‐Keiser MD , Qin C , Thompson AM , Foreman RD . Upper thoracic postsynaptic dorsal column neurons conduct cardiac mechanoreceptive information, but not cardiac chemical nociception in rats. Brain Res 1366: 71‐84, 2010.
 130. Greenwood‐Van Meerveld B , Gibson M , Gunter W , Shepard J , Foreman R , Myers D . Stereotaxic delivery of corticosterone to the amygdala modulates colonic sensitivity in rats. Brain Res 893: 135‐142, 2001.
 131. Gunter WD , Shepard JD , Foreman RD , Myers DA , Greenwood‐Van Meerveld B . Evidence for visceral hypersensitivity in high anxiety rats. Physiol Behav 69: 379‐382, 2000.
 132. Guo Z , Niu Y‐L , Zhang J‐W , Yao T‐P . Coronary artery occlusion alters expression of substance P and its mRNA in spinal dorsal horn in rats. Neuroscience 145: 669‐675, 2007.
 133. Gutterman DD . Silent myocardial ischemia. Circ J 73: 785‐97, 2009.
 134. Gutterman DD , Morgan DA , Miller FJ . Effect of brief myocardial ischemia on sympathetic coronary vasoconstriction. Circ Res 71: 960‐969, 1992.
 135. Habler HJ , Janig W , Koltzenburg M . Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat. J Physiol (Lond) 425: 545‐562, 1990.
 136. Hammond DL , Proudfit HK . Effects of locus coeruleus lesions on morphine‐induced antinociception. Brain Res 188: 79‐91, 1980.
 137. Hampton AG , Beckwith JR , Wood JE . The relationship between heart disease and gallbladder disease. Ann Intern Med 50: 1135‐1148, 1959.
 138. Hancock MB , Fougerousse CL . Spinal projections from the nucleus locus coeruleus and nucleus subcoeruleus in the cat and monkey as demonstrated by the retrograde transport of horseradish peroxidase. Brain Res Bull 1: 229‐234, 1976.
 139. Harrison TR & Reeves TJ . Patterns and causes of chest pain. In: Harrison TR , Reeves TJ , editor. Principles and Problems of Ischemic Heart Disease. Chicago: YearBook Medical, pp. 197‐204, 1968.
 140. Healy B . The Yentl syndrome. N Engl J Med 325: 274‐276, 1991.
 141. Hekmatpanah J . Organization of tactile dermatomes, C1 in cat. J. Neurophysiol 264: 582‐586, 1961.
 142. Herkenham M . Laminar organization of thalamic projections to the rat neocortex. Science 207: 532‐535, 1980.
 143. Herlitz J , Bång A , Karlson BW , Hartford M . Is there a gender difference in aetiology of chest pain and symptoms associated with acute myocardial infarction? Eur J Emerg Med 6: 311‐315, 1999.
 144. Hewson EG , Dalton CB , Hackshaw BT , Wu WC , Richter JE . The prevalence of abnormal esophageal test results in patients with cardiovascular disease and unexplained chest pain. Arch Intern Med 150: 965‐969, 1990.
 145. Hirsh P , Hillis L , Campbell W , Firth B , Willerson J . Release of prostaglandins and thromboxane into the coronary circulation in patients with ischemic heart disease. N Engl J Med 304: 685‐691, 1981.
 146. Hirshberg RM , Al‐Chaer ED , Lawand NB , Westlund KN , Willis WD . Is there a pathway in the posterior funiculus that signals visceral pain? Pain 67: 291‐305, 1996.
 147. Hobbs SF , Chandler MJ , Bolser DC , Foreman RD . Segmental organization of visceral and somatic input onto C3‐T6 spinothalamic tract cells of the monkey. J Neurophysiol 68: 1575‐1588, 1992.
 148. Hobbs SF , Oh UT , Chandler MJ , Foreman RD . Cardiac and abdominal vagal afferent inhibition of primate T9‐S1 spinothalamic cells. Am J Physiol 257: R889‐R895, 1989.
 149. Hobson AR , Khan RW , Sarkar S , Furlong PL , Aziz Q . Development of esophageal hypersensitivity following experimental duodenal acidification. Am J Gastroenterol 99: 813‐820, 2004.
 150. Hodge GB , Messer AL , Hill H . Effect of distension of the biliary tract on the electrocardiogram. Arch Surg 55: 710‐722, 1947.
 151. Hökfelt T , Zhang X , Weisenfeld‐Hallin Z . Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neuro Sci 17: 22‐30, 1994.
 152. Holzer P . Capsaicin: Cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43: 143‐201, 1991.
 153. Honoré P , Kamp EH , Rogers SD , Gebhart GF , Mantyh PW . Activation of lamina I spinal cord neurons that express the substance P receptor in visceral nociception and hyperalgesia. J Pain 3: 3‐11, 2002.
 154. Hopkins DA , Armour JA . Ganglionic distribution of afferent neurons innervating the canine heart and cardiopulmonary nerves. J Auton Nerv Syst 26: 213‐222, 1989.
 155. Hoover DB , Chang Y , Hancock JC , Zhang L . Actions of tachykinins within the heart and their relevance to cardiovascular disease. Jpn J Pharmacol 84: 367‐373, 2000.
 156. Hori T , Oka T , Hosoi M , Aou S . Pain modulatory actions of cytokines and prostaglandin E2 in the brain. Ann NY Acad Sci 840: 269‐281, 1998.
 157. Horie H , Yokota T . Responses of nociceptive VPL neurons to intracardiac injection of bradykinin in the cat. Brain Res 516: 161‐164, 1990.
 158. Houghton AK , Kadura S , Westlund KN . Dorsal column lesions reverse the reduction of home cage activity in rats with pancreatitis. NeuroReport 8: 3795‐3800, 1997.
 159. Hu WH , Martin CJ , Talley NJ . Intraesophageal acid perfusion sensitizes the esophagus to mechanical distension: A Barostat study. Am J Gastroenterol 95: 2189‐2194, 2000.
 160. Hu P , McLachlan EM . Long‐term changes in the distribution of galanin in dorsal root ganglia after sciatic or spinal nerve transection in rats. Neuroscience 103: 1059‐1071, 2001.
 161. Hu P , McLachlan EM . Macrophage and lymphocyte invation of dorsal root ganglia after peripheral nerve lesions in the rat. Neuroscience 112: 23‐38, 2002.
 162. Hua F , Ardell JL , Williams CA . Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia. Am J Physiol Regul Integr Comp Physiol 287: R1468‐1477, 2004.
 163. Hua F , Ricketts BA , Reifsteck A , Ardell JL , Williams CA . Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord. Am J Physiol Heart Circ Physiol 286: H1654‐H1664, 2004.
 164. Humbertson A , Zimmermann E , Leedy M . A chronological study of mitotic activity in satellite cell hyperplasia associated with chromatolytic neurons. Z Zellforsch 100: 507‐515, 1969.
 165. Ignatowski TA , Covey WC , Knight PR , Severin CM , Nickola TJ , Spengler RN . Brain‐derived TNFalpha mediates neuropathic pain. Brain Res 841: 70‐77, 1999.
 166. Janig W. (ed.). The Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge: Cambridge University Press. pp. 65‐85, 2006.
 167. Janig W . Visceral pain–still an enigma? Pain 151: 239‐240, 2010.
 168. Jaspersen D . Extra‐esophageal disorders in gastroesophageal reflux disease. Dig Dis 22: 115‐119, 2004.
 169. Ji R‐R , Berta T , Nedergaard M . Glia and pain: Is chronic pain a gliopathy? Pain 154: S10‐S28, 2013.
 170. Johnston IN , Milligan ED , Wieseler‐Frank J , Frank MG , Zapata V , Campisi J , Langer S , Martin D , Green P , Fleshner M , Leinwand L , Maier SF , Watkins LR . A role for proinflammatory cytokines and fractalkine in analgesia, tolerance, and subsequent pain facilitation induced by chronic intrathecal morphine. J Neurosci 24: 7353‐7365, 2004.
 171. Julius D , Basbaum AI . Molecular mechanisms of nociception. Nature 413: 203‐210, 2001.
 172. Junger H , Sorkin LS . Nociceptive and inflammatory effects of subcutaneous TNF alpha. Pain 85: 145‐151, 2000.
 173. Karai L , Brown DC , Mannes AJ , Connelly ST , Brown J , Gandal M , Wellisch OM , Neubert JK , Olah Z , and Iadarola MJ . Deletion of vanilloid receptor 1‐expressing primary afferent neurons for pain control. J Clin Invest 113: 1344‐1352, 2004.
 174. Katayama Y , Watkins LR , Becker DP , Hayes, RL . Non‐opiate analgesia induced by carbacol microinjection into the pontine parabrachial region of the cat. Brain Res 296: 262‐283, 1984.
 175. Kaufman MP , Baker DG , Coleridge HM , ColeridgeJC . Stimulation by bradykinin of afferent vagal C‐fibers with chemosensitive endings in the heart and aorta of the dog. Circ Res 46: 476‐484, 1980.
 176. Kellgren JH . Observations on referred pain arising from muscle. Clin Sci 3: 175‐190, 1937‐38.
 177. Kellgren JH . Somatic simulating visceral pain. Clin Sci 4: 303‐309, 1940.
 178. Kezdi P , Kordenat RK , Misra SN . Reflex inhibitory effects of vagal afferents in experimental myocardial infarction. Am J Cardiol 33: 853‐860, 1974.
 179. Khabarova AY. The Afferent Innervation of the Heart. New York: Heart Consultants Bureau, 1961.
 180. Khasabov SG , Rogers SD , Ghilardi JR , Peters CM , Mantyh PW , Simone DA . Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci 22: 9086‐9098, 2002.
 181. Kimura E , Hashimoto K , Furukawa S , Hayakawa H . Changes in bradykinin level in coronary sinus blood after the experimental occlusion of a coronary artery. Am Heart J 85: 635‐647, 1973.
 182. Kohchi K , Takebayashi S , Hiroki T , Nobuyoshi M . Significance of adventitial inflammation of the coronary artery in patients with unstable angina: Results at autopsy. Circulation 71: 709‐716, 1985.
 183. Kounis NG , Zavras GM . Histamine‐induced coronary artery spasm: The concept of allergic angina. Br J Clin Pract 45: 121‐127, 1991.
 184. Kreiner M , Okeson JP . Toothache of cardiac origin. J Orofac Pain 13: 201‐207, 1999.
 185. Kreiner M , Okeson JP , Michelis V , Lujambio M , Isberg A . Craniofacial pain as the sole symptom of cardiac ischemia: A prospective multicenter study. J Am Dent Assoc 138: 174‐179, 2007.
 186. Kuo DC , Oravitz JJ , DeGroat WC . Tracing of afferent and efferent pathways in the left inferior cardiac nerve of the cat using retrograde and transganglionic transport of horseradish peroxidase. Brain Res 321: 111‐118, 1984.
 187. Lanza GA. Cardiac syndrome X: A critical overview and future perspectives. Heart 93: 159‐166, 2007.
 188. Latremoliere A , Woolf CJ . Central sensitization: A generator of pain hypersensitivity by central neural plasticity. J Pain 10: 895‐926, 2009.
 189. Lehre KP , Danbolt NC . The number of glutamate transporter subtype molecules at glutamatergic synapses: Chemical and stereological quantification in young adult rat brain. J Neurosci 18: 8751‐8757, 1998.
 190. Lenz FA , Dougherty PM , Traill TA . Thalamic mechanisms of chest pain in the absence of cardiac pathology. Heart 75: 429‐430, 1996.
 191. Lewis T. Pain. New York: Macmillan, 1942.
 192. Levante A , Lamour Y , Guilbaud G , Besson JM . Spinothalamic cell activity in the monkey during intense nociceptive stimulation: Intra‐arterial injection of bradykinin into the limbs. Brain Res 88: 560‐564, 1975.
 193. Linderoth B , Brodin E . Tachykinin release from rat spinal cord in vitro and in vivo in response to various stimuli. Regul Pept 21: 129‐140, 1988.
 194. Lindgren I , Olivecrona H . Surgical treatment of angina pectoris. J Neurosurg 4: 19‐39, 1947.
 195. Little JM , Qin C , Farber JP , Foreman RD . Spinal cord processing of cardiac nociception: Are there sex differences between male and proestrous female rats? Brain Res 1413: 24‐31, 2011.
 196. Liuzzo JP , Ambrose JA . Chest pain from gastroesophageal reflux disease in patients with coronary artery disease. Cardiol Rev 13: 167‐173, 2005.
 197. Lombardi F , Casalone C , Della Bella P , Malfatto G , Pagani M , Malliani A . Global versus regional myocardial ischaemia: Differences in cardiovascular and sympathetic responses in cats. Cardiovasc Res 18: 14‐23, 1984.
 198. Lombardi F , Della Bella P , Casati R , Malliani A . Effects of intracoronary administration of bradykinin on the impulse activity of afferent sympathetic unmyelinated fibers with left ventricular endings in the cat. Circ Res 48: 69‐75, 1981.
 199. Løvlien M , Schei B , Gjengedal E . Are there gender differences related to symptoms of acute myocardial infarction? A Norwegian perspective. Prog Cardiovasc Nurs 21: 14‐19, 2006.
 200. Lu X , Richardson PM . Responses of macrophages in rat dorsal root ganglia following peripheral nerve injury. J. Neurocytol 22: 334‐341, 1993.
 201. Lynn RB . Mechanisms of esophageal pain. Am J Med 92: 11S‐19S, 1992.
 202. Ma QP . Expression of capsaicin receptor (VR1) by myelinated primary afferent neurons in rats. Neurosci Lett 319: 87‐90, 2002.
 203. Maixner W , Randich A . Role of the right vagal nerve trunk in antinociception. Brain Res 298: 374‐377, 1984.
 204. Maixner W , Touw KB , Brody MJ , Gebhart GF , Long JP . Factors regulating the altered pain perception in the spontaneously hypertensive rat. Brain Res 237: 137‐145, 1982.
 205. Malfertheiner P , Hallerbäck B . Clinical manifestations and complications of gastroesophageal reflux disease (GERD). Int J Clin Pract 59: 346‐355, 2005.
 206. Malliani A . Cardiovascular and sympathetic afferent fibers. Rev Physiol Biochem Pharmacol 94: 11‐74, 1982.
 207. Maseri A , Crea F , Kaski JC , and Davies G . Mechanisms and significance of cardiac ischemic pain. Prog Cardiovasc Dis 35: 1‐18, 1992.
 208. Mason P . Contributions of the medullary raphe and ventromedial reticular region to pain modulation and other homeostatic functions. Annu Rev Neurosci 24: 737‐777, 2001.
 209. Matsushita, M. , Ikeda , M. , Hosoya . Y. The location of spinal neurons with long descending axons (long descending propriospinal tract neurons) in the cat: A study with horseradish peroxidase technique. J Comp Neurol 184: 63‐80, 1979.
 210. Mayer ML , Westbrook GL . The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 28: 197‐276, 1987.
 211. McArthur SW , Wakefield H . Observations on the human electrocardiogram during experimental distension of the gallbladder. J Lab Clin Med 30: 349‐351, 1945.
 212. McMahon SB , Cafferty WB , Marchand F . Immune and glial cell factors as pain mediators and modulators. Exp Neurol 192: 444‐462, 2005.
 213. McMahon SB , Wall PD . Electrophysiological mapping of brainstem projections of spinal cord lamina I cells in the rat. Brain Res. 333: 19‐26, 1985.
 214. McNeill DL , Chandler MJ , Fu QG , Foreman RD . Projection of nodose ganglion cells to the upper cervical spinal cord in the rat. Brain Res Bull 27: 151‐155, 1991.
 215. Mehler WR , Feferman ME , Nauta WJH . Ascending axon degeneration following anterolateral cordotomy. An experimental study in the monkey. Brain 83: 718‐751, 1960.
 216. Mellow MH , Simpson AG , Watt L , Schoolmeester L , Haye OL . Esophageal acid perfusion in coronary artery disease. Induction of myocardial ischemia. Gastroenterology 85: 306‐312, 1983.
 217. Melzack R , Casey KL . Sensory, motivational and central control determinants of pain. In: Kenshalo DR , editor. The Skin Senses. Springfield, IL: Thomas, pp. 423‐443, 1968.
 218. Melzack R , Wall PD . The Challenge of Pain. New York: Basic Books, 1982.
 219. Menétrey D , Basbaum AI . Spinal and trigeminal projections to the nucleus of the solitary tract: A possible substrate for somatovisceral and viscerovisceral reflex activation. J Comp Neurol 255: 439‐450, 1987.
 220. Menétrey D , De Pommery J . Origins of spinal ascending pathways that reach central areas involved in visceroception and visceronociception in the rat. Eur J Neurosci 3: 249‐259, 1991.
 221. Methot J , Hamelin BA , Bogaty P , Arsenault M , Plante S , Poirier P . Does hormonal status influence the clinical presentation of acute coronary syndromes in women? J Women's Health (Larchmt) 13: 695‐702, 2004.
 222. Meyer RA , Campbell JN . A novel electrophysiological technique for locating cutaneous nociceptive and chemospecific receptors. Brain Res 441: 81‐86, 1988.
 223. Michaelis M , Habler HJ , Jaenig W . Silent afferents: A separate class of primary afferents? Clin Exp Pharmacol Physiol 23: 99‐105, 1996.
 224. Miller HR . The interrelationship of disease of the coronary arteries and gallbladder. Am Heart J 24: 579‐587, 1942.
 225. Miller, KE , Douglas, VD , Richards, AB , Chandler, MJ , Foreman, RD . Propriospinal neurons in the C1‐C2 spinal segments project to the L5‐S1 segments of the rat spinal cord. Brain Res Bull 47: 43‐47, 1998.
 226. Miller MR , Kasahara M . Studies on the nerve endings in the heart. Am J Anat 115: 217‐233, 1964.
 227. Milligan ED , Watkins LR . Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10: 23‐36, 2009.
 228. Minisi AJ , Thames MD . Distribution of left ventricular sympathetic afferents demonstrated by reflex responses to transmural myocardial ischemia and to intracoronary and epicardial bradykinin. Circulation 87: 240‐246, 1993.
 229. Miyazaki T , Zipes DP . Presynaptic modulation of efferent sympathetic and vagal neurotransmission in the canine heart by hypoxia, high K+, low pH, and adenosine. Possible relevance to ischemia‐induced denervation. Circ Res 66: 289‐301, 1990.
 230. Mtui EP , Anwar M , Gomez R , Reis DJ , Ruggiero DA . Projections from the nucleus tractus solitarii to the spinal cord. J Comp Neurol 337: 231‐252, 1993.
 231. Muers MF , Sleight P . Action potentials from ventricular mechanoreceptors stimulated by occlusion of the coronary sinus in the dog. J Physiol (Lond) 221: 283‐309, 1972.
 232. Murphy PG , Grondin J , Altares M , Richardson PM . Induction of interleukin‐6 in axotomized sensory neurons. J Neurosci 15: 5130‐5138, 1995.
 233. Myers DE . Vagus nerve pain referred to the craniofacial region. A case report and literature review with implications for referred cardiac pain. Br Dent J 204: 187‐189, 2008.
 234. Nauta HJ , Hewitt E , Westlund KN , Willis Jr WD . Surgical interruption of a midline dorsal column visceral pain pathway. Case report and review of the literature. J Neurosurg 86: 538‐542, 1997.
 235. Nerdrum T , Baker DG , Coleridge HM , Coleridge JCG. Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents. Am J Physiol 250: R815‐R822, 1986.
 236. Ness TJ , Metcalf AM , Gebhart GF . A psychophysiological study in humans using phasic colonic distention as a noxious visceral stimulus. Pain 43: 377‐386, 1990.
 237. Nihoyannopoulos P , Kaski JC , Crake T , Maseri A . Absence of myocardial dysfunction during pacing stress in patients with syndrome X. J Am Coll Cardiol 18: 1463‐1470, 1991.
 238. Niu Y‐L , Guo Z , Zhou R‐H . Up‐regulation of TNF‐a in neurons of dorsal root ganglia and spinal cord during coronary artery occlusion in rats. Cytokine 47: 23‐29, 2009.
 239. Nowicki D , Szulczyk P . Longitudinal distribution of negative cord dorsum potentials following stimulation of afferent fibres in the left inferior cardiac nerve. J Auton Nerv Syst 17: 185‐197, 1986.
 240. Oberg B , Thoren P . Circulatory responses to stimulation of medullated and non‐medullated afferents in the cardiac nerve of the cat. Acta Physiol Scand 87: 121‐132, 1972.
 241. Opherk D , Zebe H , Weihe E , Mall G , Durr C , Gravert B . Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms. Circulation 63: 817‐825, 1981.
 242. Ordway GA , Longhurst JC . Cardiovascular reflexes arising from the gallbladder of the cat: Effects of capsaicin, bradykinin, and distension. Circ Res 52: 26‐35, 1983.
 243. Ostrowsky K , Magnin M , Ryvlin P . Representation of pain and somatic sensation in the human insula: A study of responses to direct electrical cortical stimulation. Cereb Cortex 12: 376‐385, 2002.
 244. Paintal AS . Vagal sensory receptors and their reflex effects. Physiol Rev 53: 159‐227, 1973.
 245. Pal P , Koley J , Bhattacharyya S , Gupta JS , Koley B . Cardiac nociceptors and ischemia: Role of sympathetic afferents in cat. Jpn J Physiol 39: 131‐144, 1989.
 246. Palecek J , Paleckova V , Willis WD. Fos expression in spinothalamic and postsynaptic dorsal column neurons following noxious visceral and cutaneous stimuli. Pain 104: 249‐257, 2003.
 247. Pan HL , Longhurst JC . Lack of a role of adenosine in activation of ischemically sensitive cardiac sympathetic afferents. Am J Physiol HeartCirc Physiol 269: H106‐H113, 1995.
 248. Pan HL , Longhurst JC . Ischaemia‐sensitive sympathetic afferents innervating the gastrointestinal tract function as nociceptors in cats. J Physiol (Lond) 492: 841‐850, 1996.
 249. Pan HL , Longhurst JC , Eisenach JC , Chen SR . Role of protons in activation of cardiac sympathetic C‐fibre afferents during ischaemia in cats. J Physiol (Lond) 518: 857‐866, 1999.
 250. Pan HL , Chen SR . Myocardial ischemia recruits mechanically insensitive cardiac sympathetic afferents in cats. J Neurophysiol 87: 660‐668, 2002.
 251. Pan HL , Chen SR . Sensing tissue ischemia: Another new function for capsaicin receptors? Circulation 110: 1826‐1831, 2004.
 252. Pan HL , Khan GM , Alloway KD , and Chen SR . Resiniferatoxin induces paradoxical changes in thermal and mechanical sensitivities in rats: Mechanism of action. J Neurosci 23: 2911‐2919, 2003.
 253. Panneton WM , Burton H . Projections from the paratrigeminal nucleus and the medullary and spinal dorsal horn to the peribrachial area in the cat. Neuroscience 15: 779‐798, 1985.
 254. Panza JA , Laurienzo JM , Curiel RV . Investigation of the mechanism of chest pain in patients with angiographically normal coronary arteries using transesophageal dobutamine stress echocardiography. J Am Coll Cardiol 29: 293‐301, 1997.
 255. Pasceri V , Lanza GA , Buffon A . Role of abnormal pain sensitivity and behavioural factors in determining chest pain in syndrome X. J Am Coll Cardiol 31: 62‐66, 1998.
 256. Patel H , Rosengren A , Ekman I . 2004. Symptoms in acute coronary syndromes: Does sex make a difference? Am Heart J 148: 27‐33, 2004.
 257. Pedersen F , Pieterson A , Madsen JK , Ballegaard S , Meyer C , Trojaborg W . Elevated pain threshold in patients with effort‐induced angina pectoris and asymptomatic myocardial ischemia during exercise test. Clin Cardiol 12: 639‐642, 1989.
 258. Pedersen J , Reddy H , Funch‐Jensen P , Arendt‐Nielsen L , Gregersen H , Drewes AM . Differences between male and female responses to painful thermal and mechanical stimulation of the human esophagus. Dig Dis Sci 49: 1065‐1074, 2004.
 259. Ploghaus A , Narain C , Beckmann CF , Clare S , Bantick S , Wise R , Matthews PM , Rawlins JN , Tracey I . Exacerbation of pain by anxiety is associated with activity in a hippocampal network. J Neurosci 21: 9896‐9903, 2001.
 260. Price DD , Dubner R . Neurons that subserve the sensory‐discriminative aspects of pain. Pain 3: 307‐338, 1977.
 261. Procacci P , Zoppi M . Heart pain. In: Textook of Pain. Edinburgh: Churchill Livingstone. pp. 410‐419, 1989.
 262. Qin C , Chandler MJ , Miller KE , Foreman RD . Responses and afferent pathways of superficial and deeper c(1)‐c(2) spinal cells to intrapericardial algogenic chemicals in rats. J Neurophysiol 84: 1522‐1532, 2001.
 263. Qin C , Chandler MJ , Foreman RD . Esophagocardiac convergence onto thoracic spinal neurons: comparison of cervical and thoracic esophagus. Brain Res 1008: 193‐197, 2004.
 264. Qin C , Chandler MJ , Jou CJ , Foreman RD . Responses and afferent pathways of C1‐C2 spinal neurons to cervical and thoracic esophageal stimulation in rats. Neurophysiol 91: 2227‐2235, 2004.
 265. Qin C , Chandler MJ , Miller KE , Foreman RD . Chemical activation of cardiac receptors affects activity of superficial and deeper T3‐T4 spinal neurons in rats. Brain Res 959: 77‐85, 2003.
 266. Qin C , Farber JP , Foreman RD . Intraesophageal chemicals enhance responsiveness of upper thoracic spinal neurons to mechanical stimulation of esophagus in rats. Am J Physiol Gastrointest Liver Physiol 294: G708‐G716, 2008.
 267. Qin C , Farber JP , Miller KE , Foreman RD . Responses of thoracic spinal neurons to activation and desensitization of cardiac TRPV1‐containing afferents in rats. Am J Physiol Regul Integr Comp Physiol 291: R1700‐R1707, 2006.
 268. Qin C , Foreman RD , Farber JP . Characterization of thoracic spinal neurons with noxious convergent inputs from heart and lower airways in rats. Brain Res 1141: 84‐91, 2007.
 269. Qin C , Greenwood‐Van Meerveld B , Foreman RD . Spinal neuronal responses to urinary bladder stimulation in rats with corticosterone or aldosterone onto the amygdala. J Neurophysiol 90: 2180‐2189, 2003.
 270. Qin C , Greenwood‐Van Meerveld B , Myers DA , Foreman RD . Corticosterone acts directly at the amygdala to alter spinal neuronal activity in response to colorectal distension. J Neurophysiol 89: 1343‐1352, 2003.
 271. Qin C , Kranenburg A , Foreman RD . Descending modulation of thoracic visceroreceptive transmission by C1‐C2 spinal neurons. Auton Neurosci 114: 11‐16, 2004.
 272. Qin C , Malykhina AP , Thompson AM , Farber JP , Foreman RD . Cross‐organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux. Am J Physiol Gastrointest Liver Physiol 298: G934‐G942, 2010.
 273. Quigg M . Distribution of vagal afferent fibers of the guinea pig heart labeled by anterograde transport of conjugated horseradish peroxidase. J Auton Nerv Syst 36: 13‐24, 1991.
 274. Quigg M , Elfvin LG , Aldskogius H . Distribution of cardiac sympathetic afferent fibers in the guinea pig heart labeled by anterograde transport of wheat germ agglutinin‐horseradish peroxidase. J Auton Nerv Syst 25: 107‐118, 1988.
 275. Randall WC , Hasson DM , Brady JV . Acute cardiovascular consequences of anterior descending coronary artery occlusion in unanesthetized monkey. Proc Soc Exp Biol Med 58: 135‐140, 1978.
 276. Randich A , Aicher SA . Medullary substrates mediating antinociception produced by electrical stimulation of the vagus. Brain Res 445: 68‐76, 1988.
 277. Randich A , Ren K , Gebhart GF . Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases. J Neurophysiol 64: 1115‐1124, 1990.
 278. Randich A , Thurston CL . Antinociceptive states and hypertension. J Cardiovasc Electrophysiol 2(Suppl): S54‐S58, 1991.
 279. Ravdin IS , Fitzhugh T , Wolferth CC , Barbier EA , Ravdin GR . Relation of gallstone disease to angina pectoris. Arch Surg 70: 333‐342, 1955.
 280. Ravdin IS , Royster HP , Sanders GB . Reflexes originating in the common duct giving rise to pain simulating angina pectoris. Ann Surg 115: 1055‐1062, 1942.
 281. Recordati G , Lombardi F , Bishop VS , Malliani A . Response of type B atrial vagal receptors to changes in wall tension during atrial filling. Circ Res 36: 682‐691, 1975.
 282. Recordati G , Lombardi F , Bishop VS , Malliani A . Mechanical stimuli exciting type A atrial vagal receptors in the cat. Circ Res 38: 397‐403, 1976.
 283. Reddy H , Arendt‐Nielsen L , Staahl C , Pedersen J , Funch‐Jensen P , Gregersen H , Drewes AM . Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus. Dig Dis Sci 50: 2050‐2058, 2005.
 284. Reis SE , Holubkov R , Lee JS . Coronary flow velocity response to adenosine characterizes coronary microvascular function in women with chest pain and no obstructive coronary disease. Results from the pilot phase of the Women's Ischemia Syndrome Evaluation (WISE) study. J Am Coll Cardiol 33: 1469‐1475, 1999.
 285. Ren K , Randich A , Gebhart GF . Vagal afferent modulation of spinal nociceptive transmission in the rat. J Neurophysiol 62: 401‐415, 1989.
 286. Ren K , Randich A , Gebhart GF . Modulation of spinal nociceptive transmission from nuclei tractus solitary: a relay for effects of vagal afferent stimulation. J Neurophysiol 63: 971‐986, 1990a.
 287. Ren K , Randich A , Gebhart GF . Electrical stimulation of cervical vagal afferents. I. Central relays for modulation of spinal nociceptive transmission. J Neurophysiol 64: 1098‐1114, 1990b.
 288. Ren K , Randich A , Gebhart GF . Effects of electrical stimulation of vagal afferents on spinothalamic tract cells in the rat. Pain 44: 311‐319, 1991.
 289. Richter JE . Beyond heartburn: extraesophageal manifestations of gastroesophageal reflux disease. Am J Manag Care 7(Suppl 1): S6‐S9, 2001.
 290. Rocco MB , Nabel EG , Campbell S , Goldman L , Barry J , Mead K , Selwyn AP . Prognostic importance of myocardial ischemia detected by ambulatory monitoring in patients with stable coronary artery disease. Circulation 78: 877‐884, 1988.
 291. Roesler H . Esophageal reflex origin of myocardial infarction. Am J Med Sci 240: 159‐162, 1960.
 292. Rosa C , Chione S , Panattoni E , Mezzasalma L , Giuliano G . Comparison of pain perception in normotensives and borderline hypertensives by means of a tooth pulp‐stimulation test. J Cardiovasc Pharmacal 8(suppl5): S125‐S127, 1986.
 293. Rosano GM , Kaski JC , Arie S . Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries. Evaluation by continuous coronary sinus pH monitoring and lactate metabolism. Eur Heart J 17: 1175‐1180, 1996.
 294. Rosen SD . From heart to brain: The genesis and processing of cardiac pain. Can J Cardiol 28(2 Suppl): S7‐S19, 2012.
 295. Rosen SD , Paulesu E , Frith CD , Frackowiak RS , Davies GJ , Jones T , Camici PGl . Central nervous pathways mediating angina pectoris. The Lancet 344: 147‐150, 1994.
 296. Rosen SD , Paulesu E , Nihoyannopoulos P , Tousoulis D , Frackowiak RS , Frith CD , Jones T , Camici PG . Silent ischemia as a central problem: Regional brain activation compared in silent and painful myocardial ischemia. Ann Int Med 124: 939‐949, 1996.
 297. Rosen SD , Paulesu E , Wise RJS , Camici PG . Central neural contribution to the perception of chest pain in cardiac syndrome X. Heart 87: 513‐519, 2002.
 298. Rosen SD , Uren NG , Kaski J‐C , Tousoulis D , Davies GJ , Camici PG . Coronary vasodilator reserve, pain perception and gender in patients with syndrome X. Circulation 90: 50‐60, 1994.
 299. Rothstein JD , Dykes‐Hoberg M , Pardo CA , Bristol LA , Jin L , Kuncl RW , Kanai Y , Hediger MA , Wang Y , Schielke JP , Welty DF . Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16: 675‐686, 1996.
 300. Rozen JB , Schulkin J . From normal fear to pathological anxiety. Psychol Rev 105: 325‐350, 1998.
 301. Ruch TC . Pathophysiology of pain. In: Ruch TC , Patton HD , Woodbury JW , Towe AL , editors. Neurophysiology. Philadelphia: Saunders, pp. 350‐368, 1961.
 302. Saab CY , Wang J , Gu C , Garner KN , Al‐Chaer ED . Microglia: A newly discovered role in visceral hypersensitivity? Neuron Glia Biol 2: 271‐277, 2007.
 303. Sadikot AF , Parent A , Francois C . The center median and parafascicular thalamic nuclei project respectively to the sensorimotor and associate limbic striatal territories in the squirrel monkey. Brain Res 510: 161‐165, 1990.
 304. Sakuma Y , Ohtori S , Miyagi M , Ishikawa T , Inoue G , Doya H , Koshi T , Ito T , Yamashita M , Yamauchi K , Suzuki M , Moriya H , and Takahashi K . Up‐regulation of p55 TNF alpha‐receptor in dorsal root ganglia neurons following lumbar facet joint injury in rats. Eur Spine J 16: 1273‐1278, 2007.
 305. Sampson JJ , Cheitlin MD . Pathophysiology and differential diagnosis of cardiac pain. Prog Cardiovasc Dis 13: 507‐531, 1971.
 306. Sandler RS , Everhart JE , Donowitz M . The burden of selected digestive diseases in the United States. Gastroenterol 122: 1500‐1511, 2002.
 307. Sarkar S , Aziz Q , Woolf CJ , Hobson AR , Thompson DG . Contribution of central sensitisation to the development of non‐cardiac chest pain. Lancet 356: 1154‐1159, 2000.
 308. Sarkar S , Hobson AR , Furlong PL , Woolf CJ , Thompson DG , Aziz Q . Central neural mechanisms mediating human visceral hypersensitivity. Am J Physiol Gastrointest Liver Physiol 281: G1196‐G1202, 2001.
 309. Sarkar S , Thompson DG , Woolf CJ , Hobson AR , Millane T , Aziz Q . Patients with chest pain and occult gastroesophageal reflux demonstrate visceral pain hypersensitivity which may be partially responsive to acid suppression. Am J Gastroenterol 99: 1998‐2006, 2004.
 310. Sarkar S , Woolf CJ , Hobson AR , Thompson DG , Aziz Q . Perceptual wind‐up in the human oesophagus is enhanced by central sensitisation. Gut 55: 920‐925, 2006.
 311. Schaible HG , Jarrot B , Hope PJ , and Duggan AW . Release of immunoreactive substance P in the spinal cord during development of acute arthritis in the knee joint of the cat: A study with antibody microprobes. Brain Res 529: 214‐223, 1990.
 312. Schaible HG , Schmidt RF . Time course of mechanosensitivity changes in articular afferents during a developing experimental arthritis. J Neurophysiol 60: 2180‐2195, 1988.
 313. Schang SJ , Pepine CJ . Transient asymptomatic S‐T segment depression during daily activity. Am J Cardiol 39: 396‐402, 1977.
 314. Schofield PM , Whorwell PJ , Brooks NH , Bennett DH , Jones PE . Oesophageal function in patients with angina pectoris: A comparison of patients with normal coronary angiograms and patients with coronary artery disease. Digestion 42: 70‐78, 1989.
 315. Schultz HD , Ustinova EE . Cardiac vagal afferent stimulation by free radicals during ischaemia and reperfusion. Clin Exp Pharmacol Physiol 23: 700‐708, 1996.
 316. Schultz HD , Ustinova EE . Capsaicin receptors mediate free radical‐induced activation of cardiac afferent endings. Cardiovasc Res 38: 348‐355, 1998.
 317. Schwartz PJ , Pagani M , Lombardi F , Malliani A , Brown AM . A cardiocardiac sympathovagal reflex in the cat. Circ Res 32: 215‐220, 1973.
 318. Schweinhardt P , Kalk N , Wartolowska K . Investigation into the neural correlates of emotional augmentation of clinical pain. Neuroimage 40: 759‐766, 2008.
 319. Sengupta JN . Esophageal sensory physiology. GI Motility online (2006). doi:10.1038/gimo16.
 320. Serebro HA . The prognostic significance of the viscerocardiac reflex phenomenon. S Afr Med J 50: 769‐772, 1976.
 321. Sharkey KA , Sobrino JA , Cervero F . Evidence for a visceral afferent origin of substance P‐like immunoreactivity in lamina V of the rat thoracic spinal cord. Neuroscience 22: 1077‐1083, 1987.
 322. Shepard JD , Barron KW , Myers DA . Corticosterone delivery to the amygdala increases corticotropin‐releasing factor mRNA in the central amygdaloid nucleus and anxiety‐like behavior. Brain Res 861: 288‐295, 2000.
 323. Sheps DS , Creed F , Clouse RE . Chest pain in patients with cardiac and noncardiac disease. Psychosom Med 66: 861‐867, 2004.
 324. Sherlock S . Diseases of the Liver and Biliary System. Oxford, UK: Blackwell, 1981.
 325. Shin YK , Sohn UD , Choi MS , Kum C , Sim SS , Lee MY . Effects of rutin and harmaline on rat reflux oesophagitis. Auton Autocoid Pharmacol 22: 47‐55, 2002.
 326. Shriver JE , Stein BM , Carpenter MB . Central projections of spinal dorsal roots in the monkey: I. Cervical and upper thoracic dorsal roots. Am. J. Anat 123: 27‐74, 1968.
 327. Sleight P , Widdicombe JG . Action potentials in fibres from receptors in the epicardium and myocardium of the dog's left ventricle. J Physiol (Lond) 181: 235‐258, 1965.
 328. Steagall RJ , Sipe AL , Williams CA , Joyner WL , Singh K . Substance P release in response to cardiac ischemia from rat thoracic spinal dorsal horn is mediated by TRPV1. Neuroscience 214: 106‐119, 2012.
 329. Sugiura Y , Terul N , Hosoya Y . Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers. J Neurophysiol 62: 834‐840, 1989.
 330. Svensson O , Stenport G , Tibbling L , Wranne B . Oesophageal function and coronary angiogram in patients with disabling chest pain. Acta Med Scand 204: 173‐178, 1978.
 331. Sylvén C , Beermann B , Edlund A , Lewander R , Jonzon B , Mogensen L . Provocation of chest pain in patients with coronary insufficiency using the vasodilator adenosine. Eur Heart J 9(Suppl. N): 6‐10, 1988.
 332. Sylvén C , Beermann B , Jonzon B , Brandt R . Angina pectoris‐like pain provoked by intravenous adenosine in healthy volunteers. Br Med J 293: 227‐230, 1986.
 333. Sylvén C , Borg G , Brandt R , Beermann B , Jonzon B . Dose‐effect relationship of adenosine provoked angina pectoris like pain—a study of the psychophysical power function. Eur Heart J 9: 89‐91, 1988.
 334. Sylvén C . Angina pectoris. Clinical characteristics, neurophysiological and molecular mechanisms. Pain 36: 145‐167, 1989.
 335. Szallasi A . Autoradiographic visualization and pharmacological characterization of vanilloid (capsaicin) receptors in several species, including man. Acta Physiol Scand 629 (suppl.): 1‐68, 1995.
 336. Szallasi A Blumberg PM . Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 51: 159‐212, 1999.
 337. Takeuchi Y , Uemura M , Matsuda K , Matsushima R , Mizuno N . Parabrachial nucleus neurons projecting to the lower brainstem and the spinal cord. A study in the cat by the Fink‐Heimer and the horseradish peroxidase methods. Exp Neural 70: 403‐413, 1980.
 338. Tanimoto T , Takeda M , Matsumoto S . Suppressive effect of vagal afferents on cervical dorsal horn neurons responding to tooth pulp electrical stimulation in the rat. Exp Brain Res 145: 468‐479, 2002.
 339. Thames MD , Abboud FM . Reflex inhibition of renal sympathetic nerve activity during myocardial ischemia mediated by left ventricular receptors with vagal afferents in dogs. J Clin Invest 63: 395‐402, 1979.
 340. Thames MD , Klopfenstein HS , Abboud FM , Mark AL , Walker JL . Preferential distribution of inhibitory cardiac receptors with vagal afferents to the inferoposterior wall of the left ventricle activated during coronary occlusion in the dog. Circ Res 43: 512‐519, 1978.
 341. Thoren PN . Left ventricular receptors activated by severe asphyxia and by coronary artery occlusion. Acta Physiol Scand 85: 455‐463, 1972.
 342. Thoren PN . Activation of left ventricular receptors with non‐medullated vagal afferent fibers during occlusion of a coronary artery in the cat. Am J Cardiol 37: 1046‐1051, 1976.
 343. Thoren PN . Characteristics of left ventricular receptors with non‐ medullated vagal afferents in cats. Circ Res 40: 415‐421, 1977.
 344. Thoren PN . Role of cardiac vagal C‐fibers in cardiovascular control. Rev Physiol Biochem Pharmacol 86: 1‐94, 1979.
 345. Tjen‐A‐Looi S , Pan H‐L , Longhurst JC . Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats. J Physiol (Lond) 510: 633‐641, 1998.
 346. Tzukert A , Hasin Y , Sharav Y . Orofacial pain of cardiac origin. Oral Surg Oral Med Oral Pathol 51: 484‐486, 1981.
 347. Uchida Y , Murao S . Excitation of afferent cardiac sympathetic nerve fibers during coronary occlusion. Am J Physiol 226: 1094‐1099, 1974a.
 348. Uchida Y , Murao S . Potassium induced excitation of afferent cardiac sympathetic nerve fibers. Am J Physiol 226: 603‐607, 1974b.
 349. Uchida Y , Murao S . Afferent sympathetic nerve fibers originating in the left atrial wall. Am J Physiol 227: 753‐758, 1974c.
 350. Uchida Y , Murao S . Bradykinin induced excitation of afferent cardiac sympathetic nerve fibers. Jpn Heart J 15: 84‐91, 1974d.
 351. Uchida Y , Murao S . Acid‐induced excitation of afferent cardiac sympathetic nerve fibers. Am J Physiol 228: 27‐33, 1975.
 352. Ustinova EE , Schultz HD . Activation of cardiac vagal afferents by oxygen‐derived free radicals in rats. Circ Res 74: 895‐903, 1994.
 353. Vance WH , Bowker RC . Spinal origins of cardiac afferents from the region of the left anterior descending artery. Brain Res 258: 96‐100, 1983.
 354. Van Der Wall AC , Becker AE , Van Der Loos CM , Das PK . Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89: 36‐44, 1994.
 355. Vinik AI , Maser RE , Mitchell BD , Freeman R . Diabetic autonomic neuropathy. Diabetes Care 26: 1553‐1579, 2003.
 356. Wagner R , Myers RR . Endoneurial injection of TNF‐alpha produces neuropathic pain behaviors. NeuroReport 7: 2897‐2901, 1996.
 357. Walker JL , Thames MD , Abboud FM , Mark AL , Klopfenstein HS . Preferential distribution of inhibitory cardiac receptors in left ventricle of the dog. Am J Physiol 235: H188‐H192, 1978.
 358. Wang CC , Westlund KN . Responses of rat dorsal column neurons to pancreatic nociceptive stimulation. NeuroReport 12, 2527‐2530, 2001.
 359. Wang J , Gu C , Al‐Chaer ED . Sex hormones modulate the role of the postsynaptic dorsal column (PSDC) pathway in visceral pain. Program No. 171.14. Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience. Online, 2008.
 360. Watkins LR , Goehler LE , Relton J , Brewer MT , Maier SF . Mechanisms of tumor necrosis factor‐alpha (TNF‐alpha) hyperalgesia. Brain Res 692: 244‐250, 1995.
 361. Watkins LR , Maier SF . Beyond neurons: Evidence that immune and glial cells contribute to pathological pain states. Physiol Rev 82: 981‐1011, 2002.
 362. Webb SW , Adgey AA , Pantridge JF . Autonomic disturbances at onset of acute myocardial infarction. Br Med J Clin Res 3: 89‐92, 1972.
 363. Webster KE , Kemplay SK . Distribution of primary afferent fibres from the forelimb of the rat to the upper cervical spinal cord in relation to the location of spinothalamic neuron populations. Neurosci Lett 76: 18‐24, 1987.
 364. Westlund KN , Bowker RM , Ziegler MG , Coulter JD . Origins and terminations of descending noradrenergic projections to the spinal cord of the monkey. Brain Res 292: 1‐16, 1984.
 365. Westlund KN , Coulter JD . Descending projections of the locus coeruleus and subcoeruleus/medial parabrachial nuclei in the monkey: Axonal transport studies and dopamine hydroxylase neurocytochemistry. Brain Res Rev 2: 235‐264, 1980.
 366. White FA , Bhangoo SK , Miller RJ . Chemokines: Integrators of pain and inflammation. Nat Rev Drug Discov 4: 834‐844, 2005.
 367. White JC , Bland EF . The surgical relief of severe angina pectoris. Medicine (Baltimore 27: 1‐42, 1948.
 368. White JC , Garrey WE , Atkins, JA . Cardiac innervation: Experimental and clinical studies. Arch Surg 26: 765‐786, 1933.
 369. Willis WD , Trevino DL , Coulter JD , Maunz RA . Responses of primate spinothalamic tract neurons to natural stimulation of hindlimb. J Neurophysiol 37: 358‐372, 1974.
 370. Woolf CJ , Salter MW . Neuronal plasticity: Increasing the gain in pain. Science 288: 1765‐1769, 2000.
 371. Woolf CJ , Wiesenfeld‐Hallin Z . Substance P and calcitonin‐gene related peptide synergistically modulate the gain of the nociceptive flexor withdrawal reflex in the rat. Neurosci Lett 66: 226‐230, 1986.
 372. Wright RA , McClave SA , Petruska J . Does physiologic gastroesophageal reflux affect heart rate or rhythm? Scand J Gastroenterol 28: 1021‐1024, 1993.
 373. Wu M , Komori N , Qin C , Farber JP , Linderoth B , and Foreman RD . Sensory fibers containing vanilloid receptor‐1 (VR‐1) mediate spinal cord stimulation‐induced vasodilation. Brain Res 1107: 177‐184, 2006.
 374. Xu XJ , Dlasgaard CJ , Wiesenfeld‐Hallin Z . Spinal substance P and N‐methyl‐D‐aspartate receptors are co‐activated in the induction of central sensitization of the nociceptive flexor reflex. Neuroscience 51: 641‐648, 1992.
 375. Yezierski RP , Broton JG . Functional properties of spinomesencephalic tract (SMT) cells in the upper cervical spinal cord of the cat. Pain 45: 187‐196, 1991.
 376. Yezierski, RP , Culberson, JL , Brown, PB . Cells of origin of propriospinal connections to cat lumbosacral gray as determined with horseradish peroxidase. Exp Neurol 69: 493‐512, 1980.
 377. Yezierski RP , Schwartz RH . Response and receptive‐field properties of spinomesencephalic tract cells in the cat. J Neurophysiol 55: 76‐96, 1986.
 378. Zahner MR , Li D‐P , Chen SR , Pan H‐L . Cardiac vanilloid receptor 1‐expressing afferent nerves and their role in the cardiogenic sympathetic reflex in rats. J Physiol 551: 515‐523, 2003.
 379. Zamir N , Segal M . Hypertension‐induced analgesia: Changes in pain sensitivity in experimental hypertensive rats. Brain Res 160: 170‐173, 1979.
 380. Zamir N , Shuber E . Altered pain perception in hypertensive humans. Brain Res 201: 471‐474, 1980.
 381. Zhang J , Chandler MJ , Miller KE , Foreman RD . Cardiopulmonary spinal sympathetic afferent input does not require dorsal column pathways to excite C1‐C3 spinal cells in rats. Brain Res 771: 25‐30, 1997.
 382. Zhang J , Chandler MJ , Foreman RD . Cardiopulmonary sympathetic and vagal afferents excite C1‐C2 propriospinal cells in rats. Brain Res 969: 53‐58, 2003.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Mechanisms of Cardiac Pain
 

How to Cite

Robert D. Foreman, Kennon M. Garrett, Robert W. Blair. Mechanisms of Cardiac Pain. Compr Physiol 2015, 5: 929-960. doi: 10.1002/cphy.c140032