Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review

Stella Iacovides, Peter Kamerman, Fiona C Baker, Duncan Mitchell

10.1002/cphy.c210006

Source: Volume 11, Issue 4, October 2021

Published online: September 2021

Full Article on Wiley Online Library



Abstract

We review the known physiological mechanisms underpinning all of pain processing, sleep regulation, and pharmacology of analgesics prescribed for chronic pain. In particular, we describe how commonly prescribed analgesics act in sleep‐wake neural pathways, with potential unintended impact on sleep and/or wake function. Sleep disruption, whether pain‐ or drug‐induced, negatively impacts quality of life, mental and physical health. In the context of chronic pain, poor sleep quality heightens pain sensitivity and may affect analgesic function, potentially resulting in further analgesic need. Clinicians already have to consider factors including efficacy, abuse potential, and likely side effects when making analgesic prescribing choices. We propose that analgesic‐related sleep disruption should also be considered. The neurochemical mechanisms underlying the reciprocal relationship between pain and sleep are poorly understood, and studies investigating sleep in those with specific chronic pain conditions (including those with comorbidities) are lacking. We emphasize the importance of further work to clarify the effects (intended and unintended) of each analgesic class to inform personalized treatment decisions in patients with chronic pain. © 2021 American Physiological Society. Compr Physiol 11:2589‐2619, 2021.

Figure 1. Figure 1. (A) Sagittal view of the brain showing an overview of the location of the brain nuclei involved in the sleep‐wake cycle, and the respective major neurotransmitters. WAKEFULNESS (in red): Coordinated ascending arousal systems are required to promote wakefulness; these neural pathways require both ventral and dorsal pathways, and include the ascending activity of monoaminergic brainstem nuclei, with nuclei in the locus coeruleus [LC; the major origin of noradrenaline (NA) pathways] and the dorsal raphe nuclei [the major origin of serotonin (5‐HT) pathways], dopaminergic neurons of the ventral tegmental area, histaminergic nuclei in the posterior hypothalamus (tuberomammillary nucleus neurons), glutamatergic neurons in the medial parabrachial nucleus, and cholinergic nuclei of the pontine tegmentum and basal forebrain 194,276,297. Through the activation of histaminergic tuberomammillary nucleus neurons 77,277, activity in these arousal systems is promoted by input from orexin (hypocretin) originating in the lateral hypothalamus 45. Inhibitory rostral projections of the LC also contribute to wakefulness through the inhibition of GABAergic nuclei in the basal forebrain and ventrolateral preoptic area of the hypothalamus. Collaboratively, these systems control and maintain states of wake and arousal (and inhibit the activation of REM and NREM sleep‐promoting neurons) through their wide projections to the thalamus or the neocortex 194. SLEEP (in blue) is initiated by the ventrolateral preoptic nucleus (VLPO) and the median preoptic nucleus of the anterior hypothalamus, which contains neurons that release the inhibitory transmitter, ϒ‐aminobutyric acid (GABA) 194,276. Inhibition of activating systems occur predominantly via GABAergic neurons, which project to and inhibit activity in the parts of the brain that promote wakefulness, in particular, the ascending arousal system and the lateral hypothalamus 45,194. Indeed, during both stage N3 and REM sleep, GABA inhibits the serotonergic neurons of the dorsal raphe nucleus and the noradrenergic neurons of the LC 105,106. In addition, neurons in the basal forebrain also believed to be GABAergic neurons, and possibly somatostatin‐producing neurons 351, promote NREM sleep via projections within the basal forebrain and direct projections to the cortex 126,197. Similarly, GABAergic neurons of the parafacial zone in the rostral medulla may too promote NREM sleep by inhibiting wake‐promoting systems 276. Lastly, NREM sleep‐active neurons that contain both GABA and neuronal nitric oxide synthase (nNOS) are scattered in the cortex. The nNOS neurons are believed to respond to homeostatic drive and to synchronize slow cortical rhythms, and release GABA 276. In contrast, the generation of REM sleep appears to be regulated by a distribution of network circuits that extend across the brainstem, midbrain, and hypothalamus 232. The sublaterodorsal nucleus (SLD) in the pontine region contains glutamatergic neurons that generate the muscle atonia of REM sleep by exciting GABAergic/glycinergic neurons in the ventromedial medulla and spinal cord that hyperpolarize motor neurons. Cholinergic neurons of the pedunculopontine and laterodorsal tegmental (PPT and LDT) nuclei are also believed to promote REM sleep and may help generate the fast EEG activity observed during REM sleep. During REM sleep, these PPT and LDT cholinergic neurons likely activate the SLD neurons. During periods of wake and NREM sleep, SLD neurons are inhibited by GABAergic neurons of the ventral lateral periaqueductal gray (PAG) and adjacent lateral pontine tegmentum, as well as by the monoaminergic neurons of the LC and raphe nuclei (NA and 5‐HT) 276. Activation of hypothalamic neurons that contain melanin‐concentrating hormone facilitates the onset and maintenance of REM sleep 329. The suprachiasmatic nuclei (in black) regulate various sleep structures of the brain, either directly via neural or chemical outputs, or indirectly through melatonin (the suprachiasmatic nucleus connects to the pineal gland via the superior cervical ganglion, and the pineal gland releases melatonin). Signals from the suprachiasmatic nuclei communicate timing information to all other structures involved in the sleep‐wake cycle. Wake‐on, REM‐off Arousal systems as denoted with a # involve serotonin (also reduced discharge in NREM), noradrenaline (also reduced discharge in NREM), histamine (also reduced discharge in NREM), and orexin (also “off” in NREM). Wake‐on, REM‐on Arousal systems as denoted with a * involve acetylcholine, dopamine, and glutamate. (B) Encephalographic (EEG) and neuronal neurotransmitter activity during wakefulness, slow‐wave sleep (N3), and rapid‐eye‐movement (REM) sleep. Arrows pointing upwards (↑) indicate high neuronal firing rate, arrows pointing downwards (↓) indicate slow neuronal firing rate, ↔ arrows indicate quiescent neurotransmitter activity (virtual cessation of firing). As an explanatory example: monoaminergic neurons (noradrenaline, serotonin, histamine) generally have high rates of firing during wake (especially active wake), slow firing rates during stage N3, and a virtual cessation of firing during REM sleep. On the other hand, acetylcholinergic neurons fire readily during wakefulness and become less active as one sleeps, but, paradoxically, fire rapidly again during REM sleep.
Figure 2. Figure 2. Noradrenaline (NA) and serotonin (5‐HT) are the key neurotransmitters in the descending modulation of pain 13. Both noradrenergic and serotonergic brainstem nuclei have descending tracts to the spinal cord, that modulate spinal sensory processing 14. The locus coeruleus (LC; blue), located in the dorsolateral pontine tegmentum, projects rostrally and caudally, and its actions may be stimulatory or inhibitory depending on whether α1‐adrenoreceptors or α2‐adrenoreceptors are activated, respectively. Inhibitory caudal projections of the LC inhibit the transmission of nociceptive information through the dorsal horn to higher centers, while excitatory outputs to the serotonergic nucleus raphe magnus (NRM; red), located in the rostral ventromedial medulla, may contribute to the antinociceptive effects of that nucleus 13,14. The spinal release of 5‐HT can facilitate nociception through the activation of 5‐HT2/3 receptors 13. Alternatively, the spinal release of 5‐HT also can inhibit nociception via activation of inhibitory 5‐HT7 receptors 13,14. Pain modulation also involves other structures such as the mesencephalic periaqueductal gray (PAG; black).
Figure 3. Figure 3. Descending brainstem pain modulating noradrenergic and serotonergic pathways, and how analgesics may affect these pathways. In all panels, afferent nociceptive pathways are shown in black, descending antinociceptive (inhibitory) pathways are shown in red, and descending pro‐nociceptive (facilitatory) pathways are shown in green. Panel (A): Overview provides a summary of the pathways: noxious chemical, thermal, and mechanical stimuli activate nociceptive primary afferents that enter the dorsal horn of the spinal cord where they synapse with second‐order neurons that project, among other targets, to the midbrain periaqueductal grey (PAG), pontine locus coeruleus (LC), and brainstem reticular formation via the spinobulbar tract, and to the thalamus (and onwards to the cerebrum) via the spinothalamic tract. The frontal lobe, limbic forebrain, and hypothalamus have outputs to the PAG in the midbrain, which in turn, projects to the LC in the rostral pons and the nucleus raphe magnus in the rostral ventromedial medulla (RVM). The LC gives rise to noradrenergic projections to the dorsal horn, which inhibit the transmission of afferent nociceptive information through the dorsal horn by an α2‐adrenoreceptor mediated mechanism. The RVM gives rise to serotonergic projections to the dorsal horn that can either facilitate (5‐HT2/3 receptor mechanism) or inhibit (5‐HT7 receptor mechanism) transmission of nociceptive information rostrally. Panel (B): Opioids shows how opioids produce analgesia by inhibiting the synapse between the primary afferent nociceptor and projection neurons in the dorsal horn, and by activating descending inhibitory pathways at multiple levels of the cerebrum and brainstem, ultimately resulting in increased serotonin (5‐HT) and noradrenaline (NA) at 5‐HT7 receptors and α2‐adrenoreceptors, respectively. Opioids also inhibit activity in descending facilitatory pathways. Panel (C): Antidepressants shows the effect of tricyclic antidepressants (TCA) and serotonin and noradrenaline reuptake inhibitors (SNRI) on the descending pain modulating system. By inhibiting serotonin and noradrenaline reuptake at the spinal level, these two drug classes elevate synaptic levels of 5‐HT and NA in the spinal cord, thus facilitating the effects of descending pain modulating pathways. The analgesic effect is probably mediated primarily by the increase in NA. Panel (D): α2δ‐Calcium channel ligands shows the action of gabapentin and pregabalin on afferent and efferent nociceptive pathways. On afferent pathways, these drugs are proposed to work through state‐dependent modulation (the effect is dependent on increased activity in descending facilitatory serotonergic pathways) of the α2δ‐calcium subunit of voltage‐gated calcium channels on the central terminals of primary afferent nociceptors. This effect modulates the transmission of the nociceptive signal across the first synapse in the dorsal horn. In the descending pathways, the two drugs have been shown to increase activity in the descending NA pathways from the LC.


Figure 1. (A) Sagittal view of the brain showing an overview of the location of the brain nuclei involved in the sleep‐wake cycle, and the respective major neurotransmitters. WAKEFULNESS (in red): Coordinated ascending arousal systems are required to promote wakefulness; these neural pathways require both ventral and dorsal pathways, and include the ascending activity of monoaminergic brainstem nuclei, with nuclei in the locus coeruleus [LC; the major origin of noradrenaline (NA) pathways] and the dorsal raphe nuclei [the major origin of serotonin (5‐HT) pathways], dopaminergic neurons of the ventral tegmental area, histaminergic nuclei in the posterior hypothalamus (tuberomammillary nucleus neurons), glutamatergic neurons in the medial parabrachial nucleus, and cholinergic nuclei of the pontine tegmentum and basal forebrain 194,276,297. Through the activation of histaminergic tuberomammillary nucleus neurons 77,277, activity in these arousal systems is promoted by input from orexin (hypocretin) originating in the lateral hypothalamus 45. Inhibitory rostral projections of the LC also contribute to wakefulness through the inhibition of GABAergic nuclei in the basal forebrain and ventrolateral preoptic area of the hypothalamus. Collaboratively, these systems control and maintain states of wake and arousal (and inhibit the activation of REM and NREM sleep‐promoting neurons) through their wide projections to the thalamus or the neocortex 194. SLEEP (in blue) is initiated by the ventrolateral preoptic nucleus (VLPO) and the median preoptic nucleus of the anterior hypothalamus, which contains neurons that release the inhibitory transmitter, ϒ‐aminobutyric acid (GABA) 194,276. Inhibition of activating systems occur predominantly via GABAergic neurons, which project to and inhibit activity in the parts of the brain that promote wakefulness, in particular, the ascending arousal system and the lateral hypothalamus 45,194. Indeed, during both stage N3 and REM sleep, GABA inhibits the serotonergic neurons of the dorsal raphe nucleus and the noradrenergic neurons of the LC 105,106. In addition, neurons in the basal forebrain also believed to be GABAergic neurons, and possibly somatostatin‐producing neurons 351, promote NREM sleep via projections within the basal forebrain and direct projections to the cortex 126,197. Similarly, GABAergic neurons of the parafacial zone in the rostral medulla may too promote NREM sleep by inhibiting wake‐promoting systems 276. Lastly, NREM sleep‐active neurons that contain both GABA and neuronal nitric oxide synthase (nNOS) are scattered in the cortex. The nNOS neurons are believed to respond to homeostatic drive and to synchronize slow cortical rhythms, and release GABA 276. In contrast, the generation of REM sleep appears to be regulated by a distribution of network circuits that extend across the brainstem, midbrain, and hypothalamus 232. The sublaterodorsal nucleus (SLD) in the pontine region contains glutamatergic neurons that generate the muscle atonia of REM sleep by exciting GABAergic/glycinergic neurons in the ventromedial medulla and spinal cord that hyperpolarize motor neurons. Cholinergic neurons of the pedunculopontine and laterodorsal tegmental (PPT and LDT) nuclei are also believed to promote REM sleep and may help generate the fast EEG activity observed during REM sleep. During REM sleep, these PPT and LDT cholinergic neurons likely activate the SLD neurons. During periods of wake and NREM sleep, SLD neurons are inhibited by GABAergic neurons of the ventral lateral periaqueductal gray (PAG) and adjacent lateral pontine tegmentum, as well as by the monoaminergic neurons of the LC and raphe nuclei (NA and 5‐HT) 276. Activation of hypothalamic neurons that contain melanin‐concentrating hormone facilitates the onset and maintenance of REM sleep 329. The suprachiasmatic nuclei (in black) regulate various sleep structures of the brain, either directly via neural or chemical outputs, or indirectly through melatonin (the suprachiasmatic nucleus connects to the pineal gland via the superior cervical ganglion, and the pineal gland releases melatonin). Signals from the suprachiasmatic nuclei communicate timing information to all other structures involved in the sleep‐wake cycle. Wake‐on, REM‐off Arousal systems as denoted with a # involve serotonin (also reduced discharge in NREM), noradrenaline (also reduced discharge in NREM), histamine (also reduced discharge in NREM), and orexin (also “off” in NREM). Wake‐on, REM‐on Arousal systems as denoted with a * involve acetylcholine, dopamine, and glutamate. (B) Encephalographic (EEG) and neuronal neurotransmitter activity during wakefulness, slow‐wave sleep (N3), and rapid‐eye‐movement (REM) sleep. Arrows pointing upwards (↑) indicate high neuronal firing rate, arrows pointing downwards (↓) indicate slow neuronal firing rate, ↔ arrows indicate quiescent neurotransmitter activity (virtual cessation of firing). As an explanatory example: monoaminergic neurons (noradrenaline, serotonin, histamine) generally have high rates of firing during wake (especially active wake), slow firing rates during stage N3, and a virtual cessation of firing during REM sleep. On the other hand, acetylcholinergic neurons fire readily during wakefulness and become less active as one sleeps, but, paradoxically, fire rapidly again during REM sleep.


Figure 2. Noradrenaline (NA) and serotonin (5‐HT) are the key neurotransmitters in the descending modulation of pain 13. Both noradrenergic and serotonergic brainstem nuclei have descending tracts to the spinal cord, that modulate spinal sensory processing 14. The locus coeruleus (LC; blue), located in the dorsolateral pontine tegmentum, projects rostrally and caudally, and its actions may be stimulatory or inhibitory depending on whether α1‐adrenoreceptors or α2‐adrenoreceptors are activated, respectively. Inhibitory caudal projections of the LC inhibit the transmission of nociceptive information through the dorsal horn to higher centers, while excitatory outputs to the serotonergic nucleus raphe magnus (NRM; red), located in the rostral ventromedial medulla, may contribute to the antinociceptive effects of that nucleus 13,14. The spinal release of 5‐HT can facilitate nociception through the activation of 5‐HT2/3 receptors 13. Alternatively, the spinal release of 5‐HT also can inhibit nociception via activation of inhibitory 5‐HT7 receptors 13,14. Pain modulation also involves other structures such as the mesencephalic periaqueductal gray (PAG; black).


Figure 3. Descending brainstem pain modulating noradrenergic and serotonergic pathways, and how analgesics may affect these pathways. In all panels, afferent nociceptive pathways are shown in black, descending antinociceptive (inhibitory) pathways are shown in red, and descending pro‐nociceptive (facilitatory) pathways are shown in green. Panel (A): Overview provides a summary of the pathways: noxious chemical, thermal, and mechanical stimuli activate nociceptive primary afferents that enter the dorsal horn of the spinal cord where they synapse with second‐order neurons that project, among other targets, to the midbrain periaqueductal grey (PAG), pontine locus coeruleus (LC), and brainstem reticular formation via the spinobulbar tract, and to the thalamus (and onwards to the cerebrum) via the spinothalamic tract. The frontal lobe, limbic forebrain, and hypothalamus have outputs to the PAG in the midbrain, which in turn, projects to the LC in the rostral pons and the nucleus raphe magnus in the rostral ventromedial medulla (RVM). The LC gives rise to noradrenergic projections to the dorsal horn, which inhibit the transmission of afferent nociceptive information through the dorsal horn by an α2‐adrenoreceptor mediated mechanism. The RVM gives rise to serotonergic projections to the dorsal horn that can either facilitate (5‐HT2/3 receptor mechanism) or inhibit (5‐HT7 receptor mechanism) transmission of nociceptive information rostrally. Panel (B): Opioids shows how opioids produce analgesia by inhibiting the synapse between the primary afferent nociceptor and projection neurons in the dorsal horn, and by activating descending inhibitory pathways at multiple levels of the cerebrum and brainstem, ultimately resulting in increased serotonin (5‐HT) and noradrenaline (NA) at 5‐HT7 receptors and α2‐adrenoreceptors, respectively. Opioids also inhibit activity in descending facilitatory pathways. Panel (C): Antidepressants shows the effect of tricyclic antidepressants (TCA) and serotonin and noradrenaline reuptake inhibitors (SNRI) on the descending pain modulating system. By inhibiting serotonin and noradrenaline reuptake at the spinal level, these two drug classes elevate synaptic levels of 5‐HT and NA in the spinal cord, thus facilitating the effects of descending pain modulating pathways. The analgesic effect is probably mediated primarily by the increase in NA. Panel (D): α2δ‐Calcium channel ligands shows the action of gabapentin and pregabalin on afferent and efferent nociceptive pathways. On afferent pathways, these drugs are proposed to work through state‐dependent modulation (the effect is dependent on increased activity in descending facilitatory serotonergic pathways) of the α2δ‐calcium subunit of voltage‐gated calcium channels on the central terminals of primary afferent nociceptors. This effect modulates the transmission of the nociceptive signal across the first synapse in the dorsal horn. In the descending pathways, the two drugs have been shown to increase activity in the descending NA pathways from the LC.
References
 1.Afolalu EF, Ramlee F, Tang NKY. Effects of sleep changes on pain‐related health outcomes in the general population: A systematic review of longitudinal studies with exploratory meta‐analysis. Sleep Med Rev 39: 82‐97, 2018.
 2.Ahangari A. Prevalence of chronic pelvic pain among women: An updated review. Pain Physician 17: E141‐E147, 2014.
 3.Alexandre C, Latremoliere A, Ferreira A, Miracca G, Yamamoto M, Scammell TE, Woolf CJ. Decreased alertness due to sleep loss increases pain sensitivity in mice. Nat Med 23: 768‐774, 2017.
 4.Anaclet C, Fuller PM. Brainstem regulation of slow‐wave‐sleep. Curr Opin Neurobiol 44: 139‐143, 2017.
 5.Antonioli L, Csoka B, Fornai M, Colucci R, Kokai E, Blandizzi C, Hasko G. Adenosine and inflammation: What's new on the horizon? Drug Discov Today 19: 1051‐1068, 2014.
 6.Araujo P, Mazaro‐Costa R, Tufik S, Andersen ML. Impact of sex on hyperalgesia induced by sleep loss. Horm Behav 59: 174‐179, 2011.
 7.Arbaiza D, Vidal O. Tramadol in the treatment of neuropathic cancer pain: A double‐blind, placebo‐controlled study. Clin Drug Investig 27: 75‐83, 2007.
 8.Atweh SF, Kuhar MJ. Autoradiographic localization of opiate receptors in rat brain. II. The brain stem. Brain Res 129: 1‐12, 1977.
 9.Backonja MM. Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: A multicenter, double‐blind, placebo‐controlled trial in patients with diabetes mellitus. Epilepsia 40 (Suppl 6): S57‐S59; discussion S73‐54, 1999.
 10.Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Neurology 59: S14‐S17, 2002.
 11.Bagley EE, Vaughan CW, Christie MJ. Inhibition by adenosine receptor agonists of synaptic transmission in rat periaqueductal grey neurons. J Physiol 516 (Pt 1): 219‐225, 1999.
 12.Bannister K, Bee LA, Dickenson AH. Preclinical and early clinical investigations related to monoaminergic pain modulation. Neurotherapeutics 6: 703‐712, 2009.
 13.Bannister K, Dickenson AH. What the brain tells the spinal cord. Pain 157: 2148‐2151, 2016.
 14.Bannister K, Dickenson AH. The plasticity of descending controls in pain: Translational probing. J Physiol 595: 4159‐4166, 2017.
 15.Bantel C, Li X, Eisenach JC. Intraspinal adenosine induces spinal cord norepinephrine release in spinal nerve‐ligated rats but not in normal or sham controls. Anesthesiology 98: 1461‐1466, 2003.
 16.Barloese MC, Jennum PJ, Lund NT, Jensen RH. Sleep in cluster headache ‐ beyond a temporal rapid eye movement relationship? Eur J Neurol 22: 656‐e640, 2015.
 17.Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med 2: 297‐307, 2001.
 18.Bauer CS, Nieto‐Rostro M, Rahman W, Tran‐Van‐Minh A, Ferron L, Douglas L, Kadurin I, Sri Ranjan Y, Fernandez‐Alacid L, Millar NS, Dickenson AH, Lujan R, Dolphin AC. The increased trafficking of the calcium channel subunit alpha2delta‐1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J Neurosci 29: 4076‐4088, 2009.
 19.Bauer CS, Rahman W, Tran‐van‐Minh A, Lujan R, Dickenson AH, Dolphin AC. The anti‐allodynic alpha(2)delta ligand pregabalin inhibits the trafficking of the calcium channel alpha(2)delta‐1 subunit to presynaptic terminals in vivo. Biochem Soc Trans 38: 525‐528, 2010.
 20.Bazil CW, Dave J, Cole J, Stalvey J, Drake E. Pregabalin increases slow‐wave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav 23: 422‐425, 2012.
 21.Beaudin AE, Pun M, Yang C, Nicholl DD, Steinback CD, Slater DM, Wynne‐Edwards KE, Hanly PJ, Ahmed SB, Poulin MJ. Cyclooxygenases 1 and 2 differentially regulate blood pressure and cerebrovascular responses to acute and chronic intermittent hypoxia: Implications for sleep apnea. J Am Heart Assoc 3: e000875, 2014.
 22.Bee LA, Dickenson AH. Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 140: 209‐223, 2008.
 23.Benarroch EE. Descending monoaminergic pain modulation: Bidirectional control and clinical relevance. Neurology 71: 217‐221, 2008.
 24.Benington JH, Kodali SK, Heller HC. Stimulation of A1 adenosine receptors mimics the electroencephalographic effects of sleep deprivation. Brain Res 692: 79‐85, 1995.
 25.Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R. Opioid complications and side effects. Pain Physician 11: S105‐S120, 2008.
 26.Berridge CW, Espana RA. Synergistic sedative effects of noradrenergic alpha(1)‐ and beta‐receptor blockade on forebrain electroencephalographic and behavioral indices. Neuroscience 99: 495‐505, 2000.
 27.Bird SJ, Kuhar MJ. Iontophoretic application of opiates to the locus coeruleus. Brain Res 122: 523‐533, 1977.
 28.Biyik Z, Solak Y, Atalay H, Gaipov A, Guney F, Turk S. Gabapentin versus pregabalin in improving sleep quality and depression in hemodialysis patients with peripheral neuropathy: A randomized prospective crossover trial. Int Urol Nephrol 45: 831‐837, 2013.
 29.Bjorvatn B, Ursin R. Changes in sleep and wakefulness following 5‐HT1A ligands given systemically and locally in different brain regions. Rev Neurosci 9: 265‐273, 1998.
 30.Bjurstrom MF, Giron SE, Griffis CA. Cerebrospinal fluid cytokines and neurotrophic factors in human chronic pain populations: A comprehensive review. Pain Pract 16: 183‐203, 2016.
 31.Bohra MH, Kaushik C, Temple D, Chung SA, Shapiro CM. Weighing the balance: How analgesics used in chronic pain influence sleep? Br J Pain 8: 107‐118, 2014.
 32.Boivie J. On central pain and central pain mechanisms. Pain 38: 121‐122, 1989.
 33.Bonafide CP, Aucutt‐Walter N, Divittore N, King T, Bixler EO, Cronin AJ. Remifentanil inhibits rapid eye movement sleep but not the nocturnal melatonin surge in humans. Anesthesiology 108: 627‐633, 2008.
 34.Borbely AA, Akerstedt T, Benoit O, Holsboer F, Oswald I. Hypnotics and sleep physiology: A consensus report. European Sleep Research Society, Committee on Hypnotics and Sleep Physiology. Eur Arch Psychiatry Clin Neurosci 241: 13‐21, 1991.
 35.Boyle J, Eriksson ME, Gribble L, Gouni R, Johnsen S, Coppini DV, Kerr D. Randomized, placebo‐controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: Impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care 35: 2451‐2458, 2012.
 36.Braz J, Solorzano C, Wang X, Basbaum AI. Transmitting pain and itch messages: A contemporary view of the spinal cord circuits that generate gate control. Neuron 82: 522‐536, 2014.
 37.Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: Prevalence, impact on daily life, and treatment. Eur J Pain 10: 287‐333, 2006.
 38.Brunetti GA, Palumbo G, Morano GS, Baldacci E, Carmosino I, Annechini G, Talone R, Kiflom S, Mastrogiacomo G, Grammatico S, Chisini M, Costa A, Tendas A, Scaramucci L, Giovannini M, Niscola P, Petrucci MT, Cartoni C. Tapentadol PR for pain syndromes in real life patients with hematological malignancy. Cardiovasc Hematol Agents Med Chem 14: 68‐74, 2016.
 39.Buckley TM, Schatzberg AF. On the interactions of the hypothalamic‐pituitary‐adrenal (HPA) axis and sleep: Normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J Clin Endocrinol Metab 90: 3106‐3114, 2005.
 40.Burchiel KJ. Carbamazepine inhibits spontaneous activity in experimental neuromas. Exp Neurol 102: 249‐253, 1988.
 41.Burgess KR, Fan JL, Peebles K, Thomas K, Lucas S, Lucas R, Dawson A, Swart M, Shepherd K, Ainslie P. Exacerbation of obstructive sleep apnea by oral indomethacin. Chest 137: 707‐710, 2010.
 42.Buynak R, Rappaport SA, Rod K, Arsenault P, Heisig F, Rauschkolb C, Etropolski M. Long‐term safety and efficacy of tapentadol extended release following up to 2 years of treatment in patients with moderate to severe, chronic pain: Results of an open‐label extension trial. Clin Ther 37: 2420‐2438, 2015.
 43.Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research. Psychiatry Res 28: 193‐213, 1989.
 44.Buysse DJ, Schweitzer PK, Moul DE. Clinical pharmacology of other drugs used as hypnotics. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia, USA: Elselvier Saunders, 2005, p. 452‐467.
 45.Buysse DJ, Tyagi S. Clinical pharmacology of other drugs used as hypnotics. In: Kryger M, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philapelphia: Elsevier, 2017, p. 432‐445.
 46.Cape EG, Jones BE. Differential modulation of high‐frequency gamma‐electroencephalogram activity and sleep‐wake state by noradrenaline and serotonin microinjections into the region of cholinergic basalis neurons. J Neurosci 18: 2653‐2666, 1998.
 47.Carrillo‐Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine 27: 189‐200, 2005.
 48.Cashman JN. The mechanisms of action of NSAIDs in analgesia. Drugs 52 (Suppl 5): 13‐23, 1996.
 49.Chalon S, Pereira A, Lainey E, Vandenhende F, Watkin JG, Staner L, Granier LA. Comparative effects of duloxetine and desipramine on sleep EEG in healthy subjects. Psychopharmacology 177: 357‐365, 2005.
 50.Cheatle MD, Foster S, Pinkett A, Lesneski M, Qu D, Dhingra L. Assessing and managing sleep disturbance in patients with chronic pain. Anesthesiol Clin 34: 379‐393, 2016.
 51.Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M. Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell 98: 437‐451, 1999.
 52.Chen WW, Zhang X, Huang WJ. Pain control by melatonin: Physiological and pharmacological effects. Exp Ther Med 12: 1963‐1968, 2016.
 53.Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: A narrative review. Br J Anaesth 120: 1315‐1334, 2018.
 54.Choy EH. The role of sleep in pain and fibromyalgia. Nat Rev Rheumatol 11: 513‐520, 2015.
 55.Citera G, Arias MA, Maldonado‐Cocco JA, Lazaro MA, Rosemffet MG, Brusco LI, Scheines EJ, Cardinalli DP. The effect of melatonin in patients with fibromyalgia: A pilot study. Clin Rheumatol 19: 9‐13, 2000.
 56.Cohen MJM, Menefee LA, Doghramji K, Anderson WR, Frank ED. Sleep in chronic pain: Problems and treatments. Int Rev Psychiatry 12: 115‐127, 2000.
 57.Corder G, Castro DC, Bruchas MR, Scherrer G. Endogenous and exogenous opioids in pain. Annu Rev Neurosci 41: 453‐473, 2018.
 58.Coxib t NTC, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, Baron JA, Bombardier C, Cannon C, Farkouh ME, FitzGerald GA, Goss P, Halls H, Hawk E, Hawkey C, Hennekens C, Hochberg M, Holland LE, Kearney PM, Laine L, Lanas A, Lance P, Laupacis A, Oates J, Patrono C, Schnitzer TJ, Solomon S, Tugwell P, Wilson K, Wittes J, Baigent C. Vascular and upper gastrointestinal effects of non‐steroidal anti‐inflammatory drugs: Meta‐analyses of individual participant data from randomised trials. Lancet 382: 769‐779, 2013.
 59.Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, Young JP Jr, LaMoreaux LK, Martin SA, Sharma U, Pregabalin ‐105 Study G. Pregabalin for the treatment of fibromyalgia syndrome: Results of a randomized, double‐blind, placebo‐controlled trial. Arthritis Rheum 52: 1264‐1273, 2005.
 60.Cronin A, Keifer JC, Baghdoyan HA, Lydic R. Opioid inhibition of rapid eye movement sleep by a specific mu receptor agonist. Br J Anaesth 74: 188‐192, 1995.
 61.Cronin AJ, Keifer JC, Davies MF, King TS, Bixler EO. Postoperative sleep disturbance: Influences of opioids and pain in humans. Sleep 24: 39‐44, 2001.
 62.Cruccu G. Trigeminal neuralgia. Continuum (Minneap Minn) 23: 396‐420, 2017.
 63.Damasceno F, Skinner GO, Gomes A, Araujo PC, de Almeida OM. Systemic amitriptyline administration does not prevent the increased thermal response induced by paradoxical sleep deprivation. Pharmacol Biochem Behav 94: 51‐55, 2009.
 64.Davis JS, Lee HY, Kim J, Advani SM, Peng HL, Banfield E, Hawk ET, Chang S, Frazier‐Wood AC. Use of non‐steroidal anti‐inflammatory drugs in US adults: Changes over time and by demographic. Open Heart 4: e000550, 2017.
 65.de Haas S, Otte A, de Weerd A, van Erp G, Cohen A, van Gerven J. Exploratory polysomnographic evaluation of pregabalin on sleep disturbance in patients with epilepsy. J Clin Sleep Med 3: 473‐478, 2007.
 66.de Zanette SA, Vercelino R, Laste G, Rozisky JR, Schwertner A, Machado CB, Xavier F, de Souza IC, Deitos A, Torres IL, Caumo W. Melatonin analgesia is associated with improvement of the descending endogenous pain‐modulating system in fibromyalgia: A phase II, randomized, double‐dummy, controlled trial. BMC Pharmacol Toxicol 15: 40, 2014.
 67.Demarco GJ, Baghdoyan HA, Lydic R. Differential cholinergic activation of G proteins in rat and mouse brainstem: Relevance for sleep and nociception. J Comp Neurol 457: 175‐184, 2003.
 68.Denoyer M, Sallanon M, Kitahama K, Aubert C, Jouvet M. Reversibility of para‐chlorophenylalanine‐induced insomnia by intrahypothalamic microinjection of L‐5‐hydroxytryptophan. Neuroscience 28: 83‐94, 1989.
 69.Dimsdale JE, Norman D, DeJardin D, Wallace MS. The effect of opioids on sleep architecture. J Clin Sleep Med 3: 33‐36, 2007.
 70.D'Mello R, Dickenson AH. Spinal cord mechanisms of pain. Br J Anaesth 101: 8‐16, 2008.
 71.Dolezal BA, Neufeld EV, Boland DM, Martin JL, Cooper CB. Interrelationship between sleep and exercise: A systematic review. Adv Prev Med 2017: 1364387, 2017.
 72.Dooley DJ, Donovan CM, Pugsley TA. Stimulus‐dependent modulation of [(3)H]norepinephrine release from rat neocortical slices by gabapentin and pregabalin. J Pharmacol Exp Ther 295: 1086‐1093, 2000.
 73.Dooley DJ, Mieske CA, Borosky SA. Inhibition of K(+)‐evoked glutamate release from rat neocortical and hippocampal slices by gabapentin. Neurosci Lett 280: 107‐110, 2000.
 74.Dubel SJ, Altier C, Chaumont S, Lory P, Bourinet E, Nargeot J. Plasma membrane expression of T‐type calcium channel alpha(1) subunits is modulated by high voltage‐activated auxiliary subunits. J Biol Chem 279: 29263‐29269, 2004.
 75.Durcan L, Wilson F, Cunnane G. The effect of exercise on sleep and fatigue in rheumatoid arthritis: A randomized controlled study. J Rheumatol 41: 1966‐1973, 2014.
 76.Eacret D, Veasey SC, Blendy JA. Bidirectional relationship between opioids and disrupted sleep: Putative mechanisms. Mol Pharmacol 98: 445‐453, 2020.
 77.Eriksson KS, Sergeeva O, Brown RE, Haas HL. Orexin/hypocretin excites the histaminergic neurons of the tuberomammillary nucleus. J Neurosci 21: 9273‐9279, 2001.
 78.Errante LD, Petroff OA. Acute effects of gabapentin and pregabalin on rat forebrain cellular GABA, glutamate, and glutamine concentrations. Seizure 12: 300‐306, 2003.
 79.Espana RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep 34: 845‐858, 2011.
 80.Fennema J, Petrykiv S, de Jonge L, Arts M. Efficacy and safety of antidepressants as analgesics in chronic pain: A review. Eur Psychiatry 41: S234, 2017.
 81.Feoktistov I, Biaggioni I. Role of adenosine A(2B) receptors in inflammation. Adv Pharmacol 61: 115‐144, 2011.
 82.Ferdousi M, Finn DP. Stress‐induced modulation of pain: Role of the endogenous opioid system. Prog Brain Res 239: 121‐177, 2018.
 83.Ferracioli‐Oda E, Qawasmi A, Bloch MH. Meta‐analysis: Melatonin for the treatment of primary sleep disorders. PLoS One 8: e63773, 2013.
 84.Ferrari LL, Agostinelli LJ, Krashes MJ, Lowell BB, Scammell TE, Arrigoni E. Dynorphin inhibits basal forebrain cholinergic neurons by pre‐ and postsynaptic mechanisms. J Physiol 594: 1069‐1085, 2016.
 85.Fillingim RB, Bruehl S, Dworkin RH, Dworkin SF, Loeser JD, Turk DC, Widerstrom‐Noga E, Arnold L, Bennett R, Edwards RR, Freeman R, Gewandter J, Hertz S, Hochberg M, Krane E, Mantyh PW, Markman J, Neogi T, Ohrbach R, Paice JA, Porreca F, Rappaport BA, Smith SM, Smith TJ, Sullivan MD, Verne GN, Wasan AD, Wesselmann U. The ACTTION‐American Pain Society Pain Taxonomy (AAPT): An evidence‐based and multidimensional approach to classifying chronic pain conditions. J Pain 15: 241‐249, 2014.
 86.Finan PH, Buenaver LF, Coryell VT, Smith MT. Cognitive‐behavioral therapy for comorbid insomnia and chronic pain. Sleep Med Clin 9: 261‐274, 2014.
 87.Finan PH, Goodin BR, Smith MT. The association of sleep and pain: An update and a path forward. J Pain 14: 1539‐1552, 2013.
 88.Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: A systematic review and meta‐analysis. Lancet Neurol 14: 162‐173, 2015.
 89.Flik G, Folgering JH, Cremers TI, Westerink BH, Dremencov E. Interaction between brain histamine and serotonin, norepinephrine, and dopamine systems: In vivo microdialysis and electrophysiology study. J Mol Neurosci 56: 320‐328, 2015.
 90.Florete OG, Xiang J, Vorsanger GJ. Effects of extended‐release tramadol on pain‐related sleep parameters in patients with osteoarthritis. Expert Opin Pharmacother 9: 1817‐1827, 2008.
 91.Foldvary‐Schaefer N, De Leon Sanchez I, Karafa M, Mascha E, Dinner D, Morris HH. Gabapentin increases slow‐wave sleep in normal adults. Epilepsia 43: 1493‐1497, 2002.
 92.Frolich JC. A classification of NSAIDs according to the relative inhibition of cyclooxygenase isoenzymes. Trends Pharmacol Sci 18: 30‐34, 1997.
 93.Galley HF, McCormick B, Wilson KL, Lowes DA, Colvin L, Torsney C. Melatonin limits paclitaxel‐induced mitochondrial dysfunction in vitro and protects against paclitaxel‐induced neuropathic pain in the rat. J Pineal Res 63: e12444, 2017.
 94.Gan TJ, Habib AS. Adenosine as a non‐opioid analgesic in the perioperative setting. Anesth Analg 105: 487‐494, 2007.
 95.Garcia‐Borreguero D, Larrosa O, de la Llave Y, Verger K, Masramon X, Hernandez G. Treatment of restless legs syndrome with gabapentin: A double‐blind, cross‐over study. Neurology 59: 1573‐1579, 2002.
 96.Garcia‐Borreguero D, Larrosa O, Williams AM, Albares J, Pascual M, Palacios JC, Fernandez C. Treatment of restless legs syndrome with pregabalin: A double‐blind, placebo‐controlled study. Neurology 74: 1897‐1904, 2010.
 97.Garcia‐Rayado G, Navarro M, Lanas A. NSAID induced gastrointestinal damage and designing GI‐sparing NSAIDs. Expert Rev Clin Pharmacol 11: 1031‐1043, 2018.
 98.Gauthier EA, Guzick SE, Brummett CM, Baghdoyan HA, Lydic R. Buprenorphine disrupts sleep and decreases adenosine concentrations in sleep‐regulating brain regions of Sprague Dawley rat. Anesthesiology 115: 743‐753, 2011.
 99.Gautier‐Veyret E, Arnaud C, Back M, Pepin JL, Petri MH, Baguet JP, Tamisier R, Levy P, Stanke‐Labesque F. Intermittent hypoxia‐activated cyclooxygenase pathway: Role in atherosclerosis. Eur Respir J 42: 404‐413, 2013.
 100.Ge F, Mu P, Guo R, Cai L, Liu Z, Dong Y, Huang YH. Chronic sleep fragmentation enhances habenula cholinergic neural activity. Mol Psychiatry 26: 941‐954, 2019.
 101.Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN. The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem 271: 5768‐5776, 1996.
 102.Gelgor L, Cartmell S, Mitchell D. Intracerebroventricular micro‐injections of non‐steroidal anti‐inflammatory drugs abolish reperfusion hyperalgesia in the rat's tail. Pain 50: 323‐329, 1992.
 103.Gengo F. Effects of ibuprofen on sleep quality as measured using polysomnography and subjective measures in healthy adults. Clin Ther 28: 1820‐1826, 2006.
 104.Gerozissis K, De Saint Hilaire Z, Orosco M, Rouch C, Nicolaidis S. Changes in hypothalamic prostaglandin E2 may predict the occurrence of sleep or wakefulness as assessed by parallel EEG and microdialysis in the rat. Brain Res 689: 239‐244, 1995.
 105.Gervasoni D, Darracq L, Fort P, Souliere F, Chouvet G, Luppi PH. Electrophysiological evidence that noradrenergic neurons of the rat locus coeruleus are tonically inhibited by GABA during sleep. Eur J Neurosci 10: 964‐970, 1998.
 106.Gervasoni D, Peyron C, Rampon C, Barbagli B, Chouvet G, Urbain N, Fort P, Luppi PH. Role and origin of the GABAergic innervation of dorsal raphe serotonergic neurons. J Neurosci 20: 4217‐4225, 2000.
 107.Gierbolini J, Giarratano M, Benbadis SR. Carbamazepine‐related antiepileptic drugs for the treatment of epilepsy ‐ a comparative review. Expert Opin Pharmacother 17: 885‐888, 2016.
 108.Gigli GL, Placidi F, Diomedi M, Maschio M, Silvestri G, Scalise A, Marciani MG. Nocturnal sleep and daytime somnolence in untreated patients with temporal lobe epilepsy: Changes after treatment with controlled‐release carbamazepine. Epilepsia 38: 696‐701, 1997.
 109.Gilron I, Jensen TS, Dickenson AH. Combination pharmacotherapy for management of chronic pain: From bench to bedside. Lancet Neurol 12: 1084‐1095, 2013.
 110.Goadsby PJ, Dodick DW, Almas M, Diener HC, Tfelt‐Hansen P, Lipton RB, Parsons B. Treatment‐emergent CNS symptoms following triptan therapy are part of the attack. Cephalalgia 27: 254‐262, 2007.
 111.Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health 11: 770, 2011.
 112.Goncalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla‐Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 87: 1127‐1132, 2016.
 113.Greco MA, Fuller PM, Jhou TC, Martin‐Schild S, Zadina JE, Hu Z, Shiromani P, Lu J. Opioidergic projections to sleep‐active neurons in the ventrolateral preoptic nucleus. Brain Res 1245: 96‐107, 2008.
 114.Haack M, Lee E, Cohen DA, Mullington JM. Activation of the prostaglandin system in response to sleep loss in healthy humans: Potential mediator of increased spontaneous pain. Pain 145: 136‐141, 2009.
 115.Haack M, Simpson N, Sethna N, Kaur S, Mullington J. Sleep deficiency and chronic pain: Potential underlying mechanisms and clinical implications. Neuropsychopharmacology 45: 205‐216, 2020.
 116.Haas H, Panula P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci 4: 121‐130, 2003.
 117.Habib AS, Minkowitz H, Osborn T, Ogunnaike B, Candiotti K, Viscusi E, Gu J, Creed MR, Gan TJ, Adenosine Study G. Phase 2, double‐blind, placebo‐controlled, dose‐response trial of intravenous adenosine for perioperative analgesia. Anesthesiology 109: 1085‐1091, 2008.
 118.Hakki Onen S, Alloui A, Jourdan D, Eschalier A, Dubray C. Effects of rapid eye movement (REM) sleep deprivation on pain sensitivity in the rat. Brain Res 900: 261‐267, 2001.
 119.Hambrecht‐Wiedbusch VS, Gabel M, Liu LJ, Imperial JP, Colmenero AV, Vanini G. Preemptive caffeine administration blocks the increase in postoperative pain caused by previous sleep loss in the rat: A potential role for preoptic adenosine A2A receptors in sleep‐pain interactions. Sleep: 40, 2017.
 120.Hannonen P, Malminiemi K, Yli‐Kerttula U, Isomeri R, Roponen P. A randomized, double‐blind, placebo‐controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder. Br J Rheumatol 37: 1279‐1286, 1998.
 121.Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M. Double‐blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology 50: 1842‐1846, 1998.
 122.Hardeland R. Antioxidative protection by melatonin: Multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 27: 119‐130, 2005.
 123.Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi‐Perumal SR. Melatonin–a pleiotropic, orchestrating regulator molecule. Prog Neurobiol 93: 350‐384, 2011.
 124.Hartmann E, Cravens J. The effects of long term administration of psychotropic drugs on human sleep. 3. The effects of amitriptyline. Psychopharmacologia 33: 185‐202, 1973.
 125.Harvey MT, Kline RHT, May ME, Roberts AC, Valdovinos MG, Wiley RG, Kennedy CH. Parametric analysis of thermal preference following sleep deprivation in the rat. Neurosci Lett 485: 98‐101, 2010.
 126.Hassani OK, Lee MG, Henny P, Jones BE. Discharge profiles of identified GABAergic in comparison to cholinergic and putative glutamatergic basal forebrain neurons across the sleep‐wake cycle. J Neurosci 29: 11828‐11840, 2009.
 127.Hauser W, Bernardy K, Uceyler N, Sommer C. Treatment of fibromyalgia syndrome with gabapentin and pregabalin–a meta‐analysis of randomized controlled trials. Pain 145: 69‐81, 2009.
 128.Hayaishi O. Molecular genetic studies on sleep‐wake regulation, with special emphasis on the prostaglandin D(2) system. J Appl Physiol 92: 863‐868, 2002.
 129.Hayaishi O, Urade Y. Prostaglandin D2 in sleep‐wake regulation: Recent progress and perspectives. Neuroscientist 8: 12‐15, 2002.
 130.Hayashida M, Fukuda K, Fukunaga A. Clinical application of adenosine and ATP for pain control. J Anesth 19: 225‐235, 2005.
 131.Hedqvist P. Basic mechanisms of prostaglandin action on autonomic neurotransmission. Annu Rev Pharmacol Toxicol 17: 259‐279, 1977.
 132.Hendrich J, Van Minh AT, Heblich F, Nieto‐Rostro M, Watschinger K, Striessnig J, Wratten J, Davies A, Dolphin AC. Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci U S A 105: 3628‐3633, 2008.
 133.Herrero Babiloni A, Beetz G, Bruneau A, Martel MO, Cistulli PA, Nixdorf DR, Conway JM, Lavigne GJ. Multitargeting the sleep‐pain interaction with pharmacological approaches: A narrative review with suggestions on new avenues of investigation. Sleep Med Rev 59: 101459, 2021.
 134.Hicks RA, Coleman DD, Ferrante F, Sahatjian M, Hawkins J. Pain thresholds in rats during recovery from REM sleep deprivation. Percept Mot Skills 48: 687‐690, 1979.
 135.Hicks RA, Moore JD, Findley P, Hirshfield C, Humphrey V. REM sleep deprivation and pain thresholds in rats. Percept Mot Skills 47: 848‐850, 1978.
 136.Hill CM, Balkenohl M, Thomas DW, Walker R, Mathe H, Murray G. Pregabalin in patients with postoperative dental pain. Eur J Pain 5: 119‐124, 2001.
 137.Hindmarch I, Dawson J, Stanley N. A double‐blind study in healthy volunteers to assess the effects on sleep of pregabalin compared with alprazolam and placebo. Sleep 28: 187‐193, 2005.
 138.Hori T, Oka T, Hosoi M, Aou S. Pain modulatory actions of cytokines and prostaglandin E2 in the brain. Ann N Y Acad Sci 840: 269‐281, 1998.
 139.Horne JA, Percival JE, Traynor JR. Aspirin and human sleep. Electroencephalogr Clin Neurophysiol 49: 409‐413, 1980.
 140.Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O. Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine. Nat Neurosci 8: 858‐859, 2005.
 141.Huang ZL, Urade Y, Hayaishi O. Prostaglandins and adenosine in the regulation of sleep and wakefulness. Curr Opin Pharmacol 7: 33‐38, 2007.
 142.Huang ZL, Urade Y, Hayaishi O. The role of adenosine in the regulation of sleep. Curr Top Med Chem 11: 1047‐1057, 2011.
 143.Hussain SA, Al K II, Jasim NA, Gorial FI. Adjuvant use of melatonin for treatment of fibromyalgia. J Pineal Res 50: 267‐271, 2011.
 144.Hutchinson MR, Shavit Y, Grace PM, Rice KC, Maier SF, Watkins LR. Exploring the neuroimmunopharmacology of opioids: An integrative review of mechanisms of central immune signaling and their implications for opioid analgesia. Pharmacol Rev 63: 772‐810, 2011.
 145.Iacovides S, George K, Kamerman P, Baker FC. Sleep fragmentation hypersensitizes healthy young women to deep and superficial experimental pain. J Pain 18: 844‐854, 2017.
 146.Imeri L, Bianchi S, Angeli P, Mancia M. Selective blockade of different brain stem muscarinic receptor subtypes: Effects on the sleep‐wake cycle. Brain Res 636: 68‐72, 1994.
 147.Imeri L, Opp MR. How (and why) the immune system makes us sleep. Nat Rev Neurosci 10: 199‐210, 2009.
 148.Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain 18: S3‐S13, 2002.
 149.Irwin MR, Olmstead R, Carrillo C, Sadeghi N, Fitzgerald JD, Ranganath VK, Nicassio PM. Sleep loss exacerbates fatigue, depression, and pain in rheumatoid arthritis. Sleep 35: 537‐543, 2012.
 150.Ishii Y, Sumi T. Amitriptyline inhibits striatal efflux of neurotransmitters via blockade of voltage‐dependent Na+ channels. Eur J Pharmacol 221: 377‐380, 1992.
 151.Islam F, Watanabe Y, Morii H, Hayaishi O. Inhibition of rat brain prostaglandin D synthase by inorganic selenocompounds. Arch Biochem Biophys 289: 161‐166, 1991.
 152.Jain SV, Glauser TA. Effects of epilepsy treatments on sleep architecture and daytime sleepiness: An evidence‐based review of objective sleep metrics. Epilepsia 55: 26‐37, 2014.
 153.Jensen TS. Opioids in the brain: Supraspinal mechanisms in pain control. Acta Anaesthesiol Scand 41: 123‐132, 1997.
 154.Johns MW. A new method for measuring daytime sleepiness: The Epworth sleepiness scale. Sleep 14: 540‐545, 1991.
 155.Jones EJ. Basic mechanisms of sleep. In: Kryger M, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia, USA: Elsevier Saunders, 2005, p. 136‐153.
 156.Joshi I, Taylor CP. Pregabalin action at a model synapse: Binding to presynaptic calcium channel alpha2‐delta subunit reduces neurotransmission in mice. Eur J Pharmacol 553: 82‐88, 2006.
 157.Jurna I, Brune K. Central effect of the non‐steroid anti‐inflammatory agents, indomethacin, ibuprofen, and diclofenac, determined in C fibre‐evoked activity in single neurones of the rat thalamus. Pain 41: 71‐80, 1990.
 158.Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non‐cancer pain: Systematic review of efficacy and safety. Pain 112: 372‐380, 2004.
 159.Kapustin D, Bhatia A, McParland A, Trivedi A, Davidson A, Brull R, Singh M. Evaluating the impact of gabapentinoids on sleep health in patients with chronic neuropathic pain: A systematic review and meta‐analysis. Pain 161: 476‐490, 2020.
 160.Kaur S, Saxena RN, Mallick BN. GABA in locus coeruleus regulates spontaneous rapid eye movement sleep by acting on GABAA receptors in freely moving rats. Neurosci Lett 223: 105‐108, 1997.
 161.Kaur T, Shyu BC. Melatonin: A new‐generation therapy for reducing chronic pain and improving sleep disorder‐related pain. Adv Exp Med Biol 1099: 229‐251, 2018.
 162.Kay DC, Pickworth WB, Neider GL. Morphine‐like insomnia from heroin in nondependent human addicts. Br J Clin Pharmacol 11: 159‐169, 1981.
 163.Keppel Hesselink JM, Schatman ME. Phenytoin and carbamazepine in trigeminal neuralgia: Marketing‐based versus evidence‐based treatment. J Pain Res 10: 1663‐1666, 2017.
 164.Kharasch ED. Opioid half‐lives and hemlines: The long and short of fashion. Anesthesiology 122: 969‐970, 2015.
 165.Klamt JG, Prado WA. Antinociception and behavioral changes induced by carbachol microinjected into identified sites of the rat brain. Brain Res 549: 9‐18, 1991.
 166.Kluge M, Schussler P, Steiger A. Duloxetine increases stage 3 sleep and suppresses rapid eye movement (REM) sleep in patients with major depression. Eur Neuropsychopharmacol 17: 527‐531, 2007.
 167.Koh WH, Pande I, Samuels A, Jones SD, Calin A. Low dose amitriptyline in ankylosing spondylitis: A short term, double blind, placebo controlled study. J Rheumatol 24: 2158‐2161, 1997.
 168.Kosinski M, Janagap C, Gajria K, Schein J, Freedman J. Pain relief and pain‐related sleep disturbance with extended‐release tramadol in patients with osteoarthritis. Curr Med Res Opin 23: 1615‐1626, 2007.
 169.Kreibich A, Reyes BA, Curtis AL, Ecke L, Chavkin C, Van Bockstaele EJ, Valentino RJ. Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa‐opiate receptors: A novel mechanism for regulating the central norepinephrine system. J Neurosci 28: 6516‐6525, 2008.
 170.Krueger JM, Pappenheimer JR, Karnovsky ML. Sleep‐promoting effects of muramyl peptides. Proc Natl Acad Sci U S A 79: 6102‐6106, 1982.
 171.Krueger JM, Rector DM, Churchill L. Sleep and cytokines. Sleep Med Clin 2: 161‐169, 2007.
 172.Kubota T, Fang J, Meltzer LT, Krueger JM. Pregabalin enhances nonrapid eye movement sleep. J Pharmacol Exp Ther 299: 1095‐1105, 2001.
 173.Kundermann B, Spernal J, Huber MT, Krieg JC, Lautenbacher S. Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers. Psychosom Med 66: 932‐937, 2004.
 174.Kushida CA, Walters AS, Becker P, Thein SG, Perkins AT, Roth T, Canafax D, Barrett RW, The XP021 Study Group. A randomized, double‐blind, placebo‐controlled, crossover study of XP13512/GSK1838262 in the treatment of patients with primary restless legs syndrome. Sleep 32: 159‐168, 2009.
 175.Lange B, Kuperwasser B, Okamoto A, Steup A, Haufel T, Ashworth J, Etropolski M. Efficacy and safety of tapentadol prolonged release for chronic osteoarthritis pain and low back pain. Adv Ther 27: 381‐399, 2010.
 176.Langford RM, Evans N. Developments in specific cyclooxygenase therapy for acute pain. Acute Pain 4: 1‐4, 2002.
 177.Langford RM, Knaggs R, Farquhar‐Smith P, Dickenson AH. Is tapentadol different from classical opioids? A review of the evidence. Br J Pain 10: 217‐221, 2016.
 178.Lautenbacher S, Kundermann B, Krieg JC. Sleep deprivation and pain perception. Sleep Med Rev 10: 357‐369, 2006.
 179.Lavie P, Nahir M, Lorber M, Scharf Y. Nonsteroidal antiinflammatory drug therapy in rheumatoid arthritis patients. Lack of association between clinical improvement and effects on sleep. Arthritis Rheum 34: 655‐659, 1991.
 180.Lavoie PA, Beauchamp G, Elie R. Tricyclic antidepressants inhibit voltage‐dependent calcium channels and Na(+)‐Ca2+ exchange in rat brain cortex synaptosomes. Can J Physiol Pharmacol 68: 1414‐1418, 1990.
 181.Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky‐Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF. Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. J Neurosci 31: 10067‐10075, 2011.
 182.Lee J, Shin HS. T‐type calcium channels and thalamocortical rhythms in sleep: A perspective from studies of T‐type calcium channel knockout mice. CNS Neurol Disord Drug Targets 6: 63‐69, 2007.
 183.Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid‐induced hyperalgesia. Pain Physician 14: 145‐161, 2011.
 184.Lee MG, Hassani OK, Jones BE. Discharge of identified orexin/hypocretin neurons across the sleep‐waking cycle. J Neurosci 25: 6716‐6720, 2005.
 185.Lentz MJ, Landis CA, Rothermel J, Shaver JL. Effects of selective slow wave sleep disruption on musculoskeletal pain and fatigue in middle aged women. J Rheumatol 26: 1586‐1592, 1999.
 186.Leo RJ, Khalid K. Antidepressants for chronic pain: Certain agents may mitigate pain associated with neuropathy, fibromyalgia, headache, and IBS. Curr Psychiatry 18: 8‐19, 2019.
 187.Lewis SA, Oswald I, Evans JI, Akindele MO. Heroin and human sleep. Electroencephalogr Clin Neurophysiol 28: 429, 1970.
 188.Lin JS, Dauvilliers Y, Arnulf I, Bastuji H, Anaclet C, Parmentier R, Kocher L, Yanagisawa M, Lehert P, Ligneau X, Perrin D, Robert P, Roux M, Lecomte JM, Schwartz JC. An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: Studies in orexin‐/‐ mice and patients. Neurobiol Dis 30: 74‐83, 2008.
 189.Little JW, Ford A, Symons‐Liguori AM, Chen Z, Janes K, Doyle T, Xie J, Luongo L, Tosh DK, Maione S, Bannister K, Dickenson AH, Vanderah TW, Porreca F, Jacobson KA, Salvemini D. Endogenous adenosine A3 receptor activation selectively alleviates persistent pain states. Brain 138: 28‐35, 2015.
 190.Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS. Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol 33: 84‐90, 2010.
 191.Loder E. Triptan therapy in migraine. N Engl J Med 363: 63‐70, 2010.
 192.Loscher W, Honack D, Taylor CP. Gabapentin increases aminooxyacetic acid‐induced GABA accumulation in several regions of rat brain. Neurosci Lett 128: 150‐154, 1991.
 193.Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev (1): CD007115, 2014.
 194.Luppi PH, Fort P. Sleep‐wake physiology. Handb Clin Neurol 160: 359‐370, 2019.
 195.Lydic R, Keifer JC, Baghdoyan HA, Becker L. Microdialysis of the pontine reticular formation reveals inhibition of acetylcholine release by morphine. Anesthesiology 79: 1003‐1012, 1993.
 196.Manfridi A, Brambilla D, Mancia M. Sleep is differently modulated by basal forebrain GABA(A) and GABA(B) receptors. Am J Physiol Regul Integr Comp Physiol 281: R170‐R175, 2001.
 197.Manns ID, Alonso A, Jones BE. Discharge properties of juxtacellularly labeled and immunohistochemically identified cholinergic basal forebrain neurons recorded in association with the electroencephalogram in anesthetized rats. J Neurosci 20: 1505‐1518, 2000.
 198.Matsumura H, Goh Y, Ueno R, Sakai T, Hayaishi O. Awaking effect of PGE2 microinjected into the preoptic area of rats. Brain Res 444: 265‐272, 1988.
 199.Matsumura H, Honda K, Choi WS, Inoue S, Sakai T, Hayaishi O. Evidence that brain prostaglandin E2 is involved in physiological sleep‐wake regulation in rats. Proc Natl Acad Sci U S A 86: 5666‐5669, 1989.
 200.Matsumura H, Nakajima T, Osaka T, Satoh S, Kawase K, Kubo E, Kantha SS, Kasahara K, Hayaishi O. Prostaglandin D2‐sensitive, sleep‐promoting zone defined in the ventral surface of the rostral basal forebrain. Proc Natl Acad Sci U S A 91: 11998‐12002, 1994.
 201.Mauriz JL, Collado PS, Veneroso C, Reiter RJ, Gonzalez‐Gallego J. A review of the molecular aspects of melatonin's anti‐inflammatory actions: Recent insights and new perspectives. J Pineal Res 54: 1‐14, 2013.
 202.May ME, Harvey MT, Valdovinos MG, Kline RHT, Wiley RG, Kennedy CH. Nociceptor and age specific effects of REM sleep deprivation induced hyperalgesia. Behav Brain Res 159: 89‐94, 2005.
 203.Mayers AG, Baldwin DS. Antidepressants and their effect on sleep. Hum Psychopharmacol 20: 533‐559, 2005.
 204.Mayo JC, Sainz RM, Tan DX, Hardeland R, Leon J, Rodriguez C, Reiter RJ. Anti‐inflammatory actions of melatonin and its metabolites, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK), in macrophages. J Neuroimmunol 165: 139‐149, 2005.
 205.McGinty D, Szymusiak R. Neural control of sleep in mammals. In: Kryger M, Roth T, Dement WC, editors. Principles and Practice of Sleep Medicine. Philadelphia, PA: Elsevier, 2017, p. 62‐77.
 206.McGinty DJ, Sterman MB. Sleep suppression after basal forebrain lesions in the cat. Science 160: 1253‐1255, 1968.
 207.Menefee LA, Cohen MJ, Anderson WR, Doghramji K, Frank ED, Lee H. Sleep disturbance and nonmalignant chronic pain: A comprehensive review of the literature. Pain Med 1: 156‐172, 2000.
 208.Minami K, Ogata J, Uezono Y. What is the main mechanism of tramadol? Naunyn Schmiedeberg's Arch Pharmacol 388: 999‐1007, 2015.
 209.Moldofsky H, Scarisbrick P. Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosom Med 38: 35‐44, 1976.
 210.Moldofsky H, Scarisbrick P, England R, Smythe H. Musculosketal symptoms and non‐REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med 37: 341‐351, 1975.
 211.Monti JM. Serotonin control of sleep‐wake behavior. Sleep Med Rev 15: 269‐281, 2011.
 212.Moore JT, Kelz MB. Opiates, sleep, and pain: The adenosinergic link. Anesthesiology 111: 1175‐1176, 2009.
 213.Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev (3): CD007076, 2009.
 214.Morssinkhof MWL, van Wylick DW, Priester‐Vink S, van der Werf YD, den Heijer M, van den Heuvel OA, Broekman BFP. Associations between sex hormones, sleep problems and depression: A systematic review. Neurosci Biobehav Rev 118: 669‐680, 2020.
 215.Mozaffari S, Rahimi R, Abdollahi M. Implications of melatonin therapy in irritable bowel syndrome: A systematic review. Curr Pharm Des 16: 3646‐3655, 2010.
 216.Murphy PJ, Badia P, Myers BL, Boecker MR, Wright KP Jr. Nonsteroidal anti‐inflammatory drugs affect normal sleep patterns in humans. Physiol Behav 55: 1063‐1066, 1994.
 217.Murphy PJ, Myers BL, Badia P. Nonsteroidal anti‐inflammatory drugs alter body temperature and suppress melatonin in humans. Physiol Behav 59: 133‐139, 1996.
 218.Nelson AM, Battersby AS, Baghdoyan HA, Lydic R. Opioid‐induced decreases in rat brain adenosine levels are reversed by inhibiting adenosine deaminase. Anesthesiology 111: 1327‐1333, 2009.
 219.Nicholas M, Vlaeyen JWS, Rief W, Barke A, Aziz Q, Benoliel R, Cohen M, Evers S, Giamberardino MA, Goebel A, Korwisi B, Perrot S, Svensson P, Wang SJ, Treede RD, IASP Taskforce for the Classification of Chronic Pain. The IASP classification of chronic pain for ICD‐11: Chronic primary pain. Pain 160: 28‐37, 2019.
 220.Nitz D, Siegel JM. GABA release in the locus coeruleus as a function of sleep/wake state. Neuroscience 78: 795‐801, 1997.
 221.Oh J, Petersen C, Walsh CM, Bittencourt JC, Neylan TC, Grinberg LT. The role of co‐neurotransmitters in sleep and wake regulation. Mol Psychiatry 24: 1284‐1295, 2019.
 222.Oishi Y, Huang ZL, Fredholm BB, Urade Y, Hayaishi O. Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non‐rapid eye movement sleep. Proc Natl Acad Sci U S A 105: 19992‐19997, 2008.
 223.Okifuji A, Hare BD. Do sleep disorders contribute to pain sensitivity? Curr Rheumatol Rep 13: 528‐534, 2011.
 224.Onen SH, Alloui A, Eschalier A, Dubray C. Vocalization thresholds related to noxious paw pressure are decreased by paradoxical sleep deprivation and increased after sleep recovery in rat. Neurosci Lett 291: 25‐28, 2000.
 225.Onen SH, Alloui A, Gross A, Eschallier A, Dubray C. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects. J Sleep Res 10: 35‐42, 2001.
 226.Onen SH, Onen F, Courpron P, Dubray C. How pain and analgesics disturb sleep. Clin J Pain 21: 422‐431, 2005.
 227.Onoe H, Watanabe Y, Ono K, Koyama Y, Hayaishi O. Prostaglandin E2 exerts an awaking effect in the posterior hypothalamus at a site distinct from that mediating its febrile action in the anterior hypothalamus. J Neurosci 12: 2715‐2725, 1992.
 228.Pandey HP, Ram A, Matsumura H, Satoh S, Hayaishi O. Circadian variations of prostaglandins D2, E2, and F2 alpha in the cerebrospinal fluid of anesthetized rats. Biochem Biophys Res Commun 213: 625‐629, 1995.
 229.Parks GS, Olivas ND, Ikrar T, Sanathara NM, Wang L, Wang Z, Civelli O, Xu X. Histamine inhibits the melanin‐concentrating hormone system: Implications for sleep and arousal. J Physiol 592: 2183‐2196, 2014.
 230.Parmentier R, Zhao Y, Perier M, Akaoka H, Lintunen M, Hou Y, Panula P, Watanabe T, Franco P, Lin JS. Role of histamine H1‐receptor on behavioral states and wake maintenance during deficiency of a brain activating system: A study using a knockout mouse model. Neuropharmacology 106: 20‐34, 2016.
 231.Patel R, Dickenson AH. Mechanisms of the gabapentinoids and alpha 2 delta‐1 calcium channel subunit in neuropathic pain. Pharmacol Res Perspect 4: e00205, 2016.
 232.Peever J, Fuller PM. The biology of REM sleep. Curr Biol 27: R1237‐R1248, 2017.
 233.Peirs C, Seal RP. Neural circuits for pain: Recent advances and current views. Science 354: 578‐584, 2016.
 234.Pentreath VW, Rees K, Owolabi OA, Philip KA, Doua F. The somnogenic T lymphocyte suppressor prostaglandin D2 is selectively elevated in cerebrospinal fluid of advanced sleeping sickness patients. Trans R Soc Trop Med Hyg 84: 795‐799, 1990.
 235.Petroff OA, Rothman DL, Behar KL, Lamoureux D, Mattson RH. The effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy. Ann Neurol 39: 95‐99, 1996.
 236.Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states–maybe it is all in their head. Best Pract Res Clin Rheumatol 25: 141‐154, 2011.
 237.Pinnock RD. Activation of kappa‐opioid receptors depresses electrically evoked excitatory postsynaptic potentials on 5‐HT‐sensitive neurones in the rat dorsal raphe nucleus in vitro. Brain Res 583: 237‐246, 1992.
 238.Pivik RT, McCarley RW, Hobson JA. Eye movement‐associated discharge in brain stem neurons during desynchronized sleep. Brain Res 121: 59‐76, 1977.
 239.Placidi F, Diomedi M, Scalise A, Marciani MG, Romigi A, Gigli GL. Effect of anticonvulsants on nocturnal sleep in epilepsy. Neurology 54: S25‐S32, 2000.
 240.Placidi F, Mattia D, Romigi A, Bassetti MA, Spanedda F, Marciani MG. Gabapentin‐induced modulation of interictal epileptiform activity related to different vigilance levels. Clin Neurophysiol 111: 1637‐1642, 2000.
 241.Porkka‐Heiskanen T. Sleep homeostasis. Curr Opin Neurobiol 23: 799‐805, 2013.
 242.Porkka‐Heiskanen T, Alanko L, Kalinchuk A, Stenberg D. Adenosine and sleep. Sleep Med Rev 6: 321‐332, 2002.
 243.Porkka‐Heiskanen T, Strecker RE, McCarley RW. Brain site‐specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep: An in vivo microdialysis study. Neuroscience 99: 507‐517, 2000.
 244.Portas CM, Bjorvatn B, Ursin R. Serotonin and the sleep/wake cycle: Special emphasis on microdialysis studies. Prog Neurobiol 60: 13‐35, 2000.
 245.Posa L, Lopez‐Canul M, Rullo L, De Gregorio D, Dominguez‐Lopez S, Kaba Aboud M, Caputi FF, Candeletti S, Romualdi P, Gobbi G. Nociceptive responses in melatonin MT2 receptor knockout mice compared to MT1 and double MT1/MT2 receptor knockout mice. J Pineal Res 69: e12671, 2020.
 246.Przybyla GW, Szychowski KA, Gminski J. Paracetamol ‐ An old drug with new mechanisms of action. Clin Exp Pharmacol Physiol 48 (1): 3‐19, 2020.
 247.Quera‐Salva MA, Claustrat B. Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged‐release formulation (Circadin((R))) in insomnia. Encéphale 44: 548‐557, 2018.
 248.Raffa RB, Buschmann H, Christoph T, Eichenbaum G, Englberger W, Flores CM, Hertrampf T, Kogel B, Schiene K, Strassburger W, Terlinden R, Tzschentke TM. Mechanistic and functional differentiation of tapentadol and tramadol. Expert Opin Pharmacother 13: 1437‐1449, 2012.
 249.Rainnie DG, Grunze HC, McCarley RW, Greene RW. Adenosine inhibition of mesopontine cholinergic neurons: Implications for EEG arousal. Science 263: 689‐692, 1994.
 250.Rains JC, Penzien DB. Chronic headache and sleep disturbance. Curr Pain Headache Rep 6: 498‐504, 2002.
 251.Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, Keefe FJ, Mogil JS, Ringkamp M, Sluka KA, Song XJ, Stevens B, Sullivan MD, Tutelman PR, Ushida T, Vader K. The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises. Pain, 2020.
 252.Ram A, Pandey HP, Matsumura H, Kasahara‐Orita K, Nakajima T, Takahata R, Satoh S, Terao A, Hayaishi O. CSF levels of prostaglandins, especially the level of prostaglandin D2, are correlated with increasing propensity towards sleep in rats. Brain Res 751: 81‐89, 1997.
 253.Rancillac A. Serotonin and sleep‐promoting neurons. Oncotarget 7: 78222‐78223, 2016.
 254.Rao ML, Clarenbach P, Vahlensieck M, Kratzschmar S. Gabapentin augments whole blood serotonin in healthy young men. J Neural Transm 73: 129‐134, 1988.
 255.Reissig JE, Rybarczyk AM. Pharmacologic treatment of opioid‐induced sedation in chronic pain. Ann Pharmacother 39: 727‐731, 2005.
 256.Rhodin A, Stridsberg M, Gordh T. Opioid endocrinopathy: A clinical problem in patients with chronic pain and long‐term oral opioid treatment. Clin J Pain 26: 374‐380, 2010.
 257.Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31: 986‐1000, 2011.
 258.Roberts LJ 2nd, Sweetman BJ, Lewis RA, Austen KF, Oates JA. Increased production of prostaglandin D2 in patients with systemic mastocytosis. N Engl J Med 303: 1400‐1404, 1980.
 259.Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic. Sleep 29: 145‐151, 2006.
 260.Romigi A, Izzi F, Marciani MG, Torelli F, Zannino S, Pisani LR, Uasone E, Corte F, Placidi F. Pregabalin as add‐on therapy induces REM sleep enhancement in partial epilepsy: A polysomnographic study. Eur J Neurol 16: 70‐75, 2009.
 261.Roth T, Arnold LM, Garcia‐Borreguero D, Resnick M, Clair AG. A review of the effects of pregabalin on sleep disturbance across multiple clinical conditions. Sleep Med Rev 18: 261‐271, 2014.
 262.Roth T, Bhadra‐Brown P, Pitman VW, Resnick EM. Pregabalin improves fibromyalgia‐related sleep disturbance. Clin J Pain 32: 308‐312, 2016.
 263.Roth T, Lankford DA, Bhadra P, Whalen E, Resnick EM. Effect of pregabalin on sleep in patients with fibromyalgia and sleep maintenance disturbance: A randomized, placebo‐controlled, 2‐way crossover polysomnography study. Arthritis Care Res (Hoboken) 64: 597‐606, 2012.
 264.Roth T, van Seventer R, Murphy TK. The effect of pregabalin on pain‐related sleep interference in diabetic peripheral neuropathy or postherpetic neuralgia: A review of nine clinical trials. Curr Med Res Opin 26: 2411‐2419, 2010.
 265.Ruoff G, Lema M. Strategies in pain management: New and potential indications for COX‐2 specific inhibitors. J Pain Symptom Manag 25: S21‐S31, 2003.
 266.Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database Syst Rev (4): CD005454, 2007.
 267.Sabatowski R, Galvez R, Cherry DA, Jacquot F, Vincent E, Maisonobe P, Versavel M, Study G. Pregabalin reduces pain and improves sleep and mood disturbances in patients with post‐herpetic neuralgia: Results of a randomised, placebo‐controlled clinical trial. Pain 109: 26‐35, 2004.
 268.Saito YC, Tsujino N, Abe M, Yamazaki M, Sakimura K, Sakurai T. Serotonergic input to orexin neurons plays a role in maintaining wakefulness and REM sleep architecture. Front Neurosci 12: 892, 2018.
 269.Salin‐Pascual RJ, Galicia‐Polo L, Drucker‐Colin R. Sleep changes after 4 consecutive days of venlafaxine administration in normal volunteers. J Clin Psychiatry 58: 348‐350, 1997.
 270.Salinsky M, Storzbach D, Oken B, Spencer D. Topiramate effects on the EEG and alertness in healthy volunteers: A different profile of antiepileptic drug neurotoxicity. Epilepsy Behav 10: 463‐469, 2007.
 271.Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 437: 1257‐1263, 2005.
 272.Sardi NF, Tobaldini G, Morais RN, Fischer L. Nucleus accumbens mediates the pronociceptive effect of sleep deprivation: The role of adenosine A2A and dopamine D2 receptors. Pain 159: 75‐84, 2018.
 273.Sastre JP, Buda C, Kitahama K, Jouvet M. Importance of the ventrolateral region of the periaqueductal gray and adjacent tegmentum in the control of paradoxical sleep as studied by muscimol microinjections in the cat. Neuroscience 74: 415‐426, 1996.
 274.Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: An american academy of sleep medicine clinical practice guideline. J Clin Sleep Med 13: 307‐349, 2017.
 275.Sawynok J. Adenosine receptor targets for pain. Neuroscience 338: 1‐18, 2016.
 276.Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron 93: 747‐765, 2017.
 277.Scammell TE, Jackson AC, Franks NP, Wisden W, Dauvilliers Y. Histamine: Neural circuits and new medications. Sleep 42: zsy183, 2019.
 278.Schjerning AM, McGettigan P, Gislason G. Cardiovascular effects and safety of (non‐aspirin) NSAIDs. Nat Rev Cardiol 17: 574‐584, 2020.
 279.Schnitzer TJ, Gray WL, Paster RZ, Kamin M. Efficacy of tramadol in treatment of chronic low back pain. J Rheumatol 27: 772‐778, 2000.
 280.Schroder W, Tzschentke TM, Terlinden R, De Vry J, Jahnel U, Christoph T, Tallarida RJ. Synergistic interaction between the two mechanisms of action of tapentadol in analgesia. J Pharmacol Exp Ther 337: 312‐320, 2011.
 281.Schug SA, Garrett WR, Gillespie G. Opioid and non‐opioid analgesics. Best Pract Res Clin Anaesthesiol 17: 91‐110, 2003.
 282.Schuh‐Hofer S, Wodarski R, Pfau DB, Caspani O, Magerl W, Kennedy JD, Treede RD. One night of total sleep deprivation promotes a state of generalized hyperalgesia: A surrogate pain model to study the relationship of insomnia and pain. Pain 154: 1613‐1621, 2013.
 283.Schwartz MD, Kilduff TS. The neurobiology of sleep and wakefulness. Psychiatr Clin North Am 38: 615‐644, 2015.
 284.Schweitzer PK, Randazzo AC. Drugs that disturb sleep and wakefulness. In: Kryger M, Roth T, DW C, editors. Principles and Practice of Sleep Medicine. Philadelphia, PA: Esevier, 2017, p. 480‐498.
 285.Schwenke K, Agbalaka A, Litzenburger B. Tapentadol prolonged release as used in clinical practice in patients with severe chronic tumor pain. J Palliat Care Med: 5, 211, 2015.
 286.Schwertner A, Conceicao Dos Santos CC, Costa GD, Deitos A, de Souza A, de Souza IC, Torres IL, da Cunha Filho JS, Caumo W. Efficacy of melatonin in the treatment of endometriosis: A phase II, randomized, double‐blind, placebo‐controlled trial. Pain 154: 874‐881, 2013.
 287.Shaw IR, Lavigne G, Mayer P, Choiniere M. Acute intravenous administration of morphine perturbs sleep architecture in healthy pain‐free young adults: A preliminary study. Sleep 28: 677‐682, 2005.
 288.Shiga Y, Minami K, Shiraishi M, Uezono Y, Murasaki O, Kaibara M, Shigematsu A. The inhibitory effects of tramadol on muscarinic receptor‐induced responses in Xenopus oocytes expressing cloned M(3) receptors. Anesth Analg 95: 1269‐1273, table of contents, 2002.
 289.Shiraishi M, Minami K, Uezono Y, Yanagihara N, Shigematsu A, Shibuya I. Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors. Br J Pharmacol 136: 207‐216, 2002.
 290.Silber MH, Becker PM, Buchfuhrer MJ, Earley CJ, Ondo WG, Walters AS, Winkelman JW. The appropriate use of opioids in the treatment of refractory restless legs syndrome. Mayo Clin Proc 93: 59‐67, 2018.
 291.Singh DR, Nag K, Shetti AN, Krishnaveni N. Tapentadol hydrochloride: A novel analgesic. Saudi J Anaesth 7: 322‐326, 2013.
 292.Smith MT, Edwards RR, McCann UD, Haythornthwaite JA. The effects of sleep deprivation on pain inhibition and spontaneous pain in women. Sleep 30: 494‐505, 2007.
 293.Smith MT, Haythornthwaite JA. How do sleep disturbance and chronic pain inter‐relate? Insights from the longitudinal and cognitive‐behavioral clinical trials literature. Sleep Med Rev 8: 119‐132, 2004.
 294.Smith MT, Perlis ML, Park A, Smith MS, Pennington J, Giles DE, Buysse DJ. Comparative meta‐analysis of pharmacotherapy and behavior therapy for persistent insomnia. Am J Psychiatry 159: 5‐11, 2002.
 295.Smith MT, Wickwire EM, Grace EG, Edwards RR, Buenaver LF, Peterson S, Klick B, Haythornthwaite JA. Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder. Sleep 32: 779‐790, 2009.
 296.Sneyd JR, Langton JA, Allan LG, Peacock JE, Rowbotham DJ. Multicentre evaluation of the adenosine agonist GR79236X in patients with dental pain after third molar extraction. Br J Anaesth 98: 672‐676, 2007.
 297.Sorooshyari S, Huerta R, de Lecea L. A framework for quantitative modeling of neural circuits involved in sleep‐to‐wake transition. Front Neurol 6: 32, 2015.
 298.Spielman AJ, Saskin P, Thorpy MJ. Treatment of chronic insomnia by restriction of time in bed. Sleep 10: 45‐56, 1987.
 299.Stahl SM, Lee‐Zimmerman C, Cartwright S, Morrissette DA. Serotonergic drugs for depression and beyond. Curr Drug Targets 14: 578‐585, 2013.
 300.Starr CJ, Sawaki L, Wittenberg GF, Burdette JH, Oshiro Y, Quevedo AS, Coghill RC. Roles of the insular cortex in the modulation of pain: Insights from brain lesions. J Neurosci 29: 2684‐2694, 2009.
 301.Steigerwald I, Muller M, Davies A, Samper D, Sabatowski R, Baron R, Rozenberg S, Szczepanska‐Szerej A, Gatti A, Kress HG. Effectiveness and safety of tapentadol prolonged release for severe, chronic low back pain with or without a neuropathic pain component: Results of an open‐label, phase 3b study. Curr Med Res Opin 28: 911‐936, 2012.
 302.Steinmiller CL, Roehrs TA, Harris E, Hyde M, Greenwald MK, Roth T. Differential effect of codeine on thermal nociceptive sensitivity in sleepy versus nonsleepy healthy subjects. Exp Clin Psychopharmacol 18: 277‐283, 2010.
 303.Straube S, Derry S, Moore RA, McQuay HJ. Pregabalin in fibromyalgia: Meta‐analysis of efficacy and safety from company clinical trial reports. Rheumatology (Oxford) 49: 706‐715, 2010.
 304.Szymusiak R, McGinty D. Sleep suppression following kainic acid‐induced lesions of the basal forebrain. Exp Neurol 94: 598‐614, 1986.
 305.Taiwo YO, Levine JD. Prostaglandins inhibit endogenous pain control mechanisms by blocking transmission at spinal noradrenergic synapses. J Neurosci 8: 1346‐1349, 1988.
 306.Taiwo YO, Levine JD. Direct cutaneous hyperalgesia induced by adenosine. Neuroscience 38: 757‐762, 1990.
 307.Takahashi K, Kayama Y, Lin JS, Sakai K. Locus coeruleus neuronal activity during the sleep‐waking cycle in mice. Neuroscience 169: 1115‐1126, 2010.
 308.Tanabe M, Takasu K, Takeuchi Y, Ono H. Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injury. J Neurosci Res 86: 3258‐3264, 2008.
 309.Tang NKY, Stella MT, Banks PDW, Sandhu HK, Berna C. The effect of opioid therapy on sleep quality in patients with chronic non‐malignant pain: A systematic review and exploratory meta‐analysis. Sleep Med Rev 45: 105‐126, 2019.
 310.Tao R, Auerbach SB. Opioid receptor subtypes differentially modulate serotonin efflux in the rat central nervous system. J Pharmacol Exp Ther 303: 549‐556, 2002.
 311.Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: The calcium channel alpha2‐delta (alpha2‐delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res 73: 137‐150, 2007.
 312.Taylor CP, Gee NS, Su TZ, Kocsis JD, Welty DF, Brown JP, Dooley DJ, Boden P, Singh L. A summary of mechanistic hypotheses of gabapentin pharmacology. Epilepsy Res 29: 233‐249, 1998.
 313.Tedeschi A, De Bellis A, Francia P, Bernini A, Perini M, Salutini E, Anichini R. Tapentadol prolonged release reduces the severe chronic ischaemic pain and improves the quality of life in patients with type 2 diabetes. J Diabetes Res 2018: 1081792, 2018.
 314.Terao A, Matsumura H, Saito M. Interleukin‐1 induces slow‐wave sleep at the prostaglandin D2‐sensitive sleep‐promoting zone in the rat brain. J Neurosci 18: 6599‐6607, 1998.
 315.Terao A, Matsumura H, Yoneda H, Saito M. Enhancement of slow‐wave sleep by tumor necrosis factor‐alpha is mediated by cyclooxygenase‐2 in rats. Neuroreport 9: 3791‐3796, 1998.
 316.Thorne C, Beaulieu AD, Callaghan DJ, O'Mahony WF, Bartlett JM, Knight R, Kraag GR, Akhras R, Piraino PS, Eisenhoffer J, Harsanyi Z, Darke AC. A randomized, double‐blind, crossover comparison of the efficacy and safety of oral controlled‐release tramadol and placebo in patients with painful osteoarthritis. Pain Res Manag 13: 93‐102, 2008.
 317.Tiede W, Magerl W, Baumgartner U, Durrer B, Ehlert U, Treede RD. Sleep restriction attenuates amplitudes and attentional modulation of pain‐related evoked potentials, but augments pain ratings in healthy volunteers. Pain 148: 36‐42, 2010.
 318.Tomim DH, Pontarolla FM, Bertolini JF, Arase M, Tobaldini G, Lima MMS, Fischer L. The pronociceptive effect of paradoxical sleep deprivation in rats: Evidence for a role of descending pain modulation mechanisms. Mol Neurobiol 53: 1706‐1717, 2016.
 319.Treede RD. The International Association for the Study of Pain definition of pain: As valid in 2018 as in 1979, but in need of regularly updated footnotes. Pain Rep 3: e643, 2018.
 320.Treede RD, Rief W, Barke A, Aziz Q, Bennett MI, Benoliel R, Cohen M, Evers S, Finnerup NB, First MB, Giamberardino MA, Kaasa S, Korwisi B, Kosek E, Lavand'homme P, Nicholas M, Perrot S, Scholz J, Schug S, Smith BH, Svensson P, Vlaeyen JWS, Wang SJ. Chronic pain as a symptom or a disease: The IASP Classification of Chronic Pain for the International Classification of Diseases (ICD‐11). Pain 160: 19‐27, 2019.
 321.Tremont‐Lukats IW, Megeff C, Backonja MM. Anticonvulsants for neuropathic pain syndromes: Mechanisms of action and place in therapy. Drugs 60: 1029‐1052, 2000.
 322.Turk DC, Dworkin RH, Revicki D, Harding G, Burke LB, Cella D, Cleeland CS, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA. Identifying important outcome domains for chronic pain clinical trials: An IMMPACT survey of people with pain. Pain 137: 276‐285, 2008.
 323.Uebele VN, Gotter AL, Nuss CE, Kraus RL, Doran SM, Garson SL, Reiss DR, Li Y, Barrow JC, Reger TS, Yang ZQ, Ballard JE, Tang C, Metzger JM, Wang SP, Koblan KS, Renger JJ. Antagonism of T‐type calcium channels inhibits high‐fat diet‐induced weight gain in mice. J Clin Invest 119: 1659‐1667, 2009.
 324.Ueno R, Honda K, Inoue S, Hayaishi O. Prostaglandin D2, a cerebral sleep‐inducing substance in rats. Proc Natl Acad Sci U S A 80: 1735‐1737, 1983.
 325.Ukponmwan OE, Rupreht J, Dzoljic M. An analgesic effect of enkephalinase inhibition is modulated by monoamine oxidase‐B and REM sleep deprivations. Naunyn Schmiedeberg's Arch Pharmacol 332: 376‐379, 1986.
 326.Ukponmwan OE, Rupreht J, Dzoljic MR. REM sleep deprivation decreases the antinociceptive property of enkephalinase‐inhibition, morphine and cold‐water‐swim. Gen Pharmacol 15: 255‐258, 1984.
 327.Unno K, Ozaki T, Mohammad S, Tsuno S, Ikeda‐Sagara M, Honda K, Ikeda M. First and second generation H(1) histamine receptor antagonists produce different sleep‐inducing profiles in rats. Eur J Pharmacol 683: 179‐185, 2012.
 328.Vadivelu N, Huang Y, Mirante B, Jacoby M, Braveman FR, Hines RL, Sinatra R. Patient considerations in the use of tapentadol for moderate to severe pain. Drug Healthc Patient Saf 5: 151‐159, 2013.
 329.Varin C, Luppi PH, Fort P. Melanin‐concentrating hormone‐expressing neurons adjust slow‐wave sleep dynamics to catalyze paradoxical (REM) sleep. Sleep 41, 2018.
 330.Vaughan CW, Ingram SL, Connor MA, Christie MJ. How opioids inhibit GABA‐mediated neurotransmission. Nature 390: 611‐614, 1997.
 331.Vetrivelan R, Kong D, Ferrari LL, Arrigoni E, Madara JC, Bandaru SS, Lowell BB, Lu J, Saper CB. Melanin‐concentrating hormone neurons specifically promote rapid eye movement sleep in mice. Neuroscience 336: 102‐113, 2016.
 332.Vidor LP, Torres IL, Custodio de Souza IC, Fregni F, Caumo W. Analgesic and sedative effects of melatonin in temporomandibular disorders: A double‐blind, randomized, parallel‐group, placebo‐controlled study. J Pain Symptom Manag 46: 422‐432, 2013.
 333.Walder B, Tramer MR, Blois R. The effects of two single doses of tramadol on sleep: A randomized, cross‐over trial in healthy volunteers. Eur J Anaesthesiol 18: 36‐42, 2001.
 334.Walker JM, Farney RJ. Are opioids associated with sleep apnea? A review of the evidence. Curr Pain Headache Rep 13: 120‐126, 2009.
 335.Walsh TD. Antidepressants in chronic pain. Clin Neuropharmacol 6: 271‐295, 1983.
 336.Wang M, Offord J, Oxender DL, Su TZ. Structural requirement of the calcium‐channel subunit alpha2delta for gabapentin binding. Biochem J 342 (Pt 2): 313‐320, 1999.
 337.Wang Q, Yue XF, Qu WM, Tan R, Zheng P, Urade Y, Huang ZL. Morphine inhibits sleep‐promoting neurons in the ventrolateral preoptic area via mu receptors and induces wakefulness in rats. Neuropsychopharmacology 38: 791‐801, 2013.
 338.Wang TX, Yin D, Guo W, Liu YY, Li YD, Qu WM, Han WJ, Hong ZY, Huang ZL. Antinociceptive and hypnotic activities of pregabalin in a neuropathic pain‐like model in mice. Pharmacol Biochem Behav 135: 31‐39, 2015.
 339.Warner TD, Giuliano F, Vojnovic I, Bukasa A, Mitchell JA, Vane JR. Nonsteroid drug selectivities for cyclo‐oxygenase‐1 rather than cyclo‐oxygenase‐2 are associated with human gastrointestinal toxicity: A full in vitro analysis. Proc Natl Acad Sci U S A 96: 7563‐7568, 1999.
 340.Webster LR, Choi Y, Desai H, Webster L, Grant BJ. Sleep‐disordered breathing and chronic opioid therapy. Pain Med 9: 425‐432, 2008.
 341.Wehling M. Non‐steroidal anti‐inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: Management and mitigation of risks and adverse effects. Eur J Clin Pharmacol 70: 1159‐1172, 2014.
 342.Whitworth TL, Quick MW. Upregulation of gamma‐aminobutyric acid transporter expression: Role of alkylated gamma‐aminobutyric acid derivatives. Biochem Soc Trans 29: 736‐741, 2001.
 343.Wichniak A, Wierzbicka A, Walecka M, Jernajczyk W. Effects of antidepressants on sleep. Curr Psychiatry Rep 19: 63, 2017.
 344.Wiffen PJ, Derry S, Bell RF, Rice AS, Tolle TR, Phillips T, Moore RA. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev 6: CD007938, 2017.
 345.Wiffen PJ, Derry S, Moore RA, Kalso EA. Carbamazepine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev (4): CD005451, 2014.
 346.Wiklund T, Linton SJ, Alfoldi P, Gerdle B. Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT‐based stress management? ‐ A randomized controlled study. BMC Musculoskelet Disord 19: 111, 2018.
 347.Wilson L, Dorosz L. Possible role of the opioid peptides in sleep. Med Hypotheses 14: 269‐280, 1984.
 348.Wilson S, Argyropoulos S. Antidepressants and sleep: A qualitative review of the literature. Drugs 65: 927‐947, 2005.
 349.Winkelman JW, Bogan RK, Schmidt MH, Hudson JD, DeRossett SE, Hill‐Zabala CE. Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome. Mov Disord 26: 2065‐2072, 2011.
 350.Xiao L, Tang YL, Smith AK, Xiang YT, Sheng LX, Chi Y, Du WJ, Guo S, Jiang ZN, Zhang GF, Luo XN. Nocturnal sleep architecture disturbances in early methadone treatment patients. Psychiatry Res 179: 91‐95, 2010.
 351.Xu M, Chung S, Zhang S, Zhong P, Ma C, Chang WC, Weissbourd B, Sakai N, Luo L, Nishino S, Dan Y. Basal forebrain circuit for sleep‐wake control. Nat Neurosci 18: 1641‐1647, 2015.
 352.Yan PZ, Butler PM, Kurowski D, Perloff MD. Beyond neuropathic pain: Gabapentin use in cancer pain and perioperative pain. Clin J Pain 30: 613‐629, 2014.
 353.Yang SR, Hu ZZ, Luo YJ, Zhao YN, Sun HX, Yin D, Wang CY, Yan YD, Wang DR, Yuan XS, Ye CB, Guo W, Qu WM, Cherasse Y, Lazarus M, Ding YQ, Huang ZL. The rostromedial tegmental nucleus is essential for non‐rapid eye movement sleep. PLoS Biol 16: e2002909, 2018.
 354.Yoshida H, Kubota T, Krueger JM. A cyclooxygenase‐2 inhibitor attenuates spontaneous and TNF‐alpha‐induced non‐rapid eye movement sleep in rabbits. Am J Physiol Regul Integr Comp Physiol 285: R99‐R109, 2003.
 355.Yoshida Y, Matsumura H, Nakajima T, Mandai M, Urakami T, Kuroda K, Yoneda H. Prostaglandin E (EP) receptor subtypes and sleep: Promotion by EP4 and inhibition by EP1/EP2. Neuroreport 11: 2127‐2131, 2000.
 356.Zondervan KT, Yudkin PL, Vessey MP, Jenkinson CP, Dawes MG, Barlow DH, Kennedy SH. The community prevalence of chronic pelvic pain in women and associated illness behaviour. Br J Gen Pract 51: 541‐547, 2001.

Contact Editor

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

* Required Field

Article Title: Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review
 

How to Cite

Stella Iacovides, Peter Kamerman, Fiona C Baker, Duncan Mitchell. Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review. Compr Physiol 2021, 11: 2589-2619. doi: 10.1002/cphy.c210006