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Le yin et le yang de la sérotonine : un Janus dans les contrôles de la douleur

Yin and yang in serotonin: Its Janus roles in pain control mechanisms

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Douleur et Analgésie

Résumé

L’implication de la sérotonine dans les contrôles physiologiques de la signalisation nociceptive est aujourd’hui bien établie. Avec la découverte de ses multiples récepteurs, de nombreux travaux ont visé à distinguer ceux impliqués dans les contrôles inhibiteurs de ceux à l’origine de modulations facilitatrices de la douleur. En réalité, selon sa localisation cellulaire ou subcellulaire, selon qu’il est auto- ou hétérorécepteur, un même type de récepteur peut générer la réduction ou, au contraire, l’exacerbation d’une douleur par la sérotonine. Cette dualité explique pourquoi l’arsenal pharmacologique ciblé sur ce neuromédiateur n’a que rarement abouti à une application thérapeutique.

Abstract

Serotonin implication in physiological controls of pain signaling is a well-established fact. The demonstration of the existence of multiple serotonin receptors led to very intense research aimed at identifying those responsible for inhibitory controls versus those mediating serotonin facilitatory controls of pain. In fact, depending on its cellular/subcellular location, its auto- or heteroreceptor function, the same receptor type can mediate opposite modulations of pain signaling. This explains why only very few drugs targeted on serotonin neurotransmission have been successfully developed for pain treatment.

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Références

  1. Hamon M, Bourgoin S (1999) Serotonin and its receptors in pain controls. In: Sawynok J, Cowan A (eds), Novel aspects of pain management: opioids and beyond. John Wiley and Sons, New York, NY, pp 203–28

    Google Scholar 

  2. Sommer C (2004) Serotonin in pain and analgesia: actions in the periphery. Mol Neurobiol 30}:117–25

    Article  CAS  PubMed  Google Scholar 

  3. Godínez-Chaparro B, Barragán-Iglesias P, Castañeda-Corral G, et al (2011) Role of peripheral 5-HT4, 5-HT6 and 5-HT7 receptors in development and maintenance of secondary mechanical allodynia and hyperalgesia. Pain 152:687–97

    Article  PubMed  CAS  Google Scholar 

  4. Sasaki M, Obata H, Kawahara K, et al (2006) Peripheral 5-HT2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury in rats. Pain 122:130–6

    Article  CAS  PubMed  Google Scholar 

  5. Millan MJ (2002) Descending control of pain. Prog Neurobiol 66:355–474

    Article  CAS  PubMed  Google Scholar 

  6. Kayser V, Bourgoin S, Viguier F, et al (2010) Toward deciphering the respective roles of multiple 5-HT receptors in the complex serotonin-mediated pain control. In: Beaulieu P, Lussier D, Porreca F, Dickenson AH (eds) Pharmacology of pain. IASP Press, Seattle, pp 185–206

    Google Scholar 

  7. Bardin L (2011) The complex role of serotonin and 5-HT receptors in chronic pain. Behav Pharmacol 22:390–404

    Article  CAS  PubMed  Google Scholar 

  8. Oyama T, Ueda M, Kuraishi Y, et al (1996) Dual effect of serotonin on formalin-induced nociception in the rat spinal cord. Neurosci Res 25:129–35

    Article  CAS  PubMed  Google Scholar 

  9. Kayser V, Elfassi IE, Aubel B, et al (2007) Mechanical, thermal and formalin-induced nociception is differentially altered in 5-HT 1A-/-, 5-HT1B-/-, 5-HT2A-/-, 5-HT3A-/- and 5-HTT-/- knock-out male mice. Pain 130:235–48

    Article  CAS  PubMed  Google Scholar 

  10. Brenchat A, Rocasalbas M, Zamanillo D, et al (2012) Assessment of 5-HT7 receptor agonists selectively using nociceptive and thermoregulation tests in knockout versus wild-type mice. Adv Pharmacol Sci 2012:312041 (9 p)

    PubMed  PubMed Central  Google Scholar 

  11. Masson J, Emerit MB, Hamon M, Darmon M (2012) Serotonergic signaling: multiple effectors and pleiotropic effects. WIREs Membr Transp Signal 1:685–713

    Article  CAS  Google Scholar 

  12. Matthys A, Haegeman G, van Craenenbroeck K, Vanhoenacker P (2011) Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives. Mol Neurobiol 43:228–53

    Article  CAS  PubMed  Google Scholar 

  13. Renner U, Zeug A, Woehler A, et al (2012) Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signaling and trafficking. J Cell Sci 125:2486–99

    Article  CAS  PubMed  Google Scholar 

  14. Hökfelt T, Ljungdahl A, Steinbusch H, et al (1978) Immunohistochemical evidence of substance P-like immunoreactivity in some 5-hydroxytryptamine-containing neurons in the rat central nervous system. Neuroscience 3:517–38

    Article  PubMed  Google Scholar 

  15. Kaneko T, Akiyama H, Nagatsu I, Mizuno N (1990) Immunohistochemical demonstration of glutaminase in catecholaminergic and serotoninergic neurons of rat brain. Brain Res 507:151–4

    Article  CAS  PubMed  Google Scholar 

  16. Stornetta RL, Guyenet PG (1999) Distribution of glutamic acid decarboxylase mRNA-containing neurons in rat medulla projecting to thoracic spinal cord in relation to monoaminergic brainstem neurons. J Comp Neurol 407:367–80

    Article  CAS  PubMed  Google Scholar 

  17. Cesselin F, Hamon M (1984) Possible functional significance of the simultaneous release of several putative neurotransmitters by the same neuron. Ann Endocrinol 45:207–13

    CAS  Google Scholar 

  18. Dahlström A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl 232:1–55

    Google Scholar 

  19. Steinbusch HW (1981) Distribution of serotonin-immunoreactivity in the central nervous system of the rat-cell bodies and terminals. Neuroscience 6:557–618

    Article  CAS  PubMed  Google Scholar 

  20. Kwiat G, Basbaum AI (1992) The origin of brainstem noradrenergic and serotonergic projections to the spinal cord dorsal horn in the rat. Somatosens Mot Res 9:157–73

    Article  CAS  PubMed  Google Scholar 

  21. Gautier A, Geny D, Bernard JF, Hamon M (2015) Superficial versus deep laminae of the dorsal horn are differentially innervated by bulbar serotonergic projections in the rat. Pain in Europe IX, Vienna, Sept 2015, Abst 0458

    Google Scholar 

  22. Hamon M (1995) Sérotonine — 5-hydroxytryptamine (5-HT). In: Epelbaum J (ed) Neuropeptides et neuromédiateurs. Sandoz, Paris, pp 261–70

    Google Scholar 

  23. Côté F, Thévet E, Fligny C et al (2003) Disruption of the nonneuronal TPH1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc Natl Acad Sci USA 100: 13525–30

  24. Narboux-Nême N, Sagné C, Doly S, et al (2011) Severe serotonin depletion after conditional deletion of the vesicular monoamine transporter 2 gene in serotonin neurons: neural and behavioral consequences. Neuropsychopharmacology 36:2538–50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Reubi JC, Emson PC, Jessell TM, Iversen LL (1978) Effects of GABA, dopamine, and substance P on the release of newly synthesized 3H-5-hydroxytryptamine from rat substantia nigra in vitro. Naunyn-Schmiedebergs Arch Pharmacol 304:271–5

    Article  CAS  PubMed  Google Scholar 

  26. Héry F, Faudon M, Ternaux JP (1982) In vivo release of serotonin in two raphe nuclei (raphe dorsalis and magnus) of the cat. Brain Res Bull 8:123–9

    Article  PubMed  Google Scholar 

  27. Adell A, Carceller A, Artigas F (1993) In vivo brain dialysis study of the somatodendritic release of serotonin in the raphe nuclei of the rat: effects of 8-hydroxy-2-(di-n-propylamino) tetralin. J Neurochem 60:1673–81

    Article  CAS  PubMed  Google Scholar 

  28. Lanfumey L, Hamon M (2004) 5-HT1 receptors. Curr Drug Targets. CNS Neurol Disord 3:1–10

    Article  CAS  PubMed  Google Scholar 

  29. Blakely RD, De Felice LJ, Hartzell HC (1994) Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 196:263–81

    CAS  PubMed  Google Scholar 

  30. Masson J, Sagné C, Hamon M, El Mestikawy S (1999) Neurotransmitter transporters in the central nervous system. Pharmacol Rev 51:439–64

    CAS  PubMed  Google Scholar 

  31. Finnerup NB, Otto M, McQuay HJ, et al (2005) Algorithm for neuropathic pain treatment: an evidence-based proposal. Pain 118:289–305

    Article  CAS  PubMed  Google Scholar 

  32. Attal N, Bouhassira D (2015) Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain 156: S104–S14

    Article  PubMed  Google Scholar 

  33. Tracey I, Mantyh PW (2007) The cerebral signature for pain perception and its modulation. Neuron 55:377–91

    Article  CAS  PubMed  Google Scholar 

  34. Apkarian AV, Hashmi JA, Baliki MN (2011) Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152:49–64

    Article  Google Scholar 

  35. Saadé NE, Jabbur SJ (2008) Nociceptive behavior in animal models for peripheral neuropathy: spinal and supraspinal mechanisms. Prog Neurobiol 86:22–47

    Article  PubMed  Google Scholar 

  36. Vogt BA (2005) Pain and emotion interactions in subregions of the cingulate gyrus. Nat Rev Neurosci 6:533–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Doan L, Manders T, Wang J (2015) Neuroplasticity underlying the comorbidity of pain and depression. Neural Plast 2015: 504691 (16 p)

    Article  PubMed  PubMed Central  Google Scholar 

  38. Harte SE, Kender RG, Borszcz GS (2005) Activation of 5-HT1A and 5-HT7 receptors in the parafascicular nucleus suppresses the affective reaction of rats to noxious stimulation. Pain 113:405–15

    Article  CAS  PubMed  Google Scholar 

  39. Xiao DQ, Zhu JX, Tang JS, Jia H (2005) GABAergic modulation mediates antinociception produced by serotonin applied into thalamic nucleus submedius of the rat. Brain Res 1057:161–7

    Article  CAS  PubMed  Google Scholar 

  40. Qu CL, Huo FQ, Huang FS, et al (2008) The role of 5-HT receptor subtypes in the ventrolateral orbital cortex of 5-HT-induced antinociception in the rat. Neuroscience 152:487–94

    Article  CAS  PubMed  Google Scholar 

  41. Monconduit L, Lopez-Avila A, Molat JL, et al (2006) Corticofugal output from the primary somatosensory cortex selectively modulates innocuous and noxious inputs in the rat spinothalamic system. J Neurosci 26:8441–50

    Article  CAS  PubMed  Google Scholar 

  42. Oliveras JL, Bourgoin S, Héry F, et al (1977) The topographical distribution of serotoninergic terminals in the spinal cord of the cat: biochemical mapping by the combined use of microdissection and microassay procedures. Brain Res 138:393–406

    Article  CAS  PubMed  Google Scholar 

  43. Mayer DJ, Liebeskind JC (1974) Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analysis. Brain Res 68:73–93

    Article  CAS  PubMed  Google Scholar 

  44. Oliveras JL, Redjemi F, Guilbaud G, Besson JM (1975) Analgesia induced by electrical stimulation of the inferior centralis nucleus of the raphe in the cat. Pain 1:139–45

    Article  CAS  PubMed  Google Scholar 

  45. Bourgoin S, Oliveras JL, Bruxelle J, et al (1980) Electrical stimulation of the nucleus raphe magnus in the rat. Effects on 5-HT metabolism in the spinal cord. Brain Res 194:377–89

    CAS  PubMed  Google Scholar 

  46. Hentall ID, Pinzon A, Noga BR (2006) Spatial and temporal patterns of serotonin release in the rat’s lumbar spinal cord following electrical stimulation of the nucleus raphe magnus. Neuroscience 142:893–903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wei F, Dubner R, Ren K (1999) Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain 80:127–41

    Article  CAS  PubMed  Google Scholar 

  48. Zhao ZQ, Chiechio S, Sun YG, et al (2007) Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs. J Neurosci 27:6045–53

    Article  CAS  PubMed  Google Scholar 

  49. Cai YQ, Wang W, Hou YY, Pan ZZ (2014) Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization. Mol Pain 10:70

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Wessendorf MW, Anderson EG (1983) Single unit studies of identified bulbospinal serotonergic units. Brain Res 279:93–103

    Article  CAS  PubMed  Google Scholar 

  51. Chiang CY, Gao B (1986) The modification by systemic morphine of the responses of serotonergic and non-serotonergic neurons in nucleus raphe magnus to heating the tail. Pain 26:245–57

    Article  CAS  PubMed  Google Scholar 

  52. Mason P (1997) Physiological identification of pontomedullary serotonergic neurons in the rat. J Neurophysiol 77:1087–98

    CAS  PubMed  Google Scholar 

  53. Winkler CW, Hermes SM, Chavkin CI, et al (2006) Kappa opioid receptor (KOR) and GAD67 immunoreactivity are found in OFF and NEUTRAL cells in the rostral ventromedial medulla. J Neurophysiol 96:3465–73

    Article  CAS  PubMed  Google Scholar 

  54. Gau R, Sevoz-Couche C, Hamon M, Bernard JF (2013) Noxious stimulation excites serotonergic neurons: a comparison between the lateral paragigantocellular reticular and the raphe magnus nuclei. Pain 154:647–59

    Article  PubMed  Google Scholar 

  55. Chen T, Dong YX, Li YQ (2003) Fos expression in serotonergic neurons in the rat brainstem following noxious stimuli: an immunohistochemical double-labelling study. J Anat 203:579–88

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gau R, Sevoz-Couche C, Laguzzi R, et al (2009) Inhibition of cardiac baroreflex by noxious thermal stimuli: a key role for lateral paragigantocellular serotonergic cells. Pain 146:315–24

    Article  PubMed  Google Scholar 

  57. Aira Z, Buesa I, Salgueiro M, et al (2010) Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury. Neuroscience 168:831–41

    Article  CAS  PubMed  Google Scholar 

  58. Muñoz-Islas E, Vidal-Cantú GC, Bravo-Hernández M, et al (2014) Spinal 5-HT5A receptors mediate 5-HT-induced antinociception in several pain models in rats. Pharmacol Biochem Behav 120:25–32

    Article  PubMed  CAS  Google Scholar 

  59. Avila-Rojas SH, Velásquez-Lagunas I, Salinas-Abarca AB, et al (2015) Role of spinal 5-HT5A and 5-HT1A/1B/1D receptors in neuropathic pain induced by spinal nerve ligation in rats. Brain Res 1622:377–85

    Article  CAS  PubMed  Google Scholar 

  60. Green GM, Scarth J, Dickenson A (2000) An excitatory role for 5-HT in spinal inflammatory nociceptive transmission: state dependent actions via dorsal horn 5-HT3 receptors in the anaesthetized rat. Pain 89:81–8

    Article  CAS  PubMed  Google Scholar 

  61. Suzuki R, Rygh LJ, Dickenson AH (2004) Bad news from the brain: descending 5-HT pathways that control spinal pain processing. Trends Pharmacol Sci 25:613–7

    Article  CAS  PubMed  Google Scholar 

  62. Neziri AY, Dickenmann M, Scaramozzino P, et al (2012) Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients. Pain 153:311–8

    Article  CAS  PubMed  Google Scholar 

  63. Bonnavion P, Bernard JF, Hamon M, et al (2010) Heterogeneous distribution of the serotonin 5-HT1A receptor mRNA in chemically identified neurons of the mouse rostral brainstem: implications for the role of serotonin in the regulation of wakefulness and REM sleep. J Comp Neurol 18:2744–70

    Google Scholar 

  64. Pierce PA, Xie GX, Meuser T, Peroutka SJ (1997) 5-hydroxytryptamine receptor subtype messenger RNAs in human dorsal root ganglia: a polymerase chain reaction study. Neuroscience 81:813–9

    Article  CAS  PubMed  Google Scholar 

  65. Wei H, Pertovaara A (2006) 5-HT1A receptors in endogenous regulation of neuropathic hypersensitivity in the rat. Eur J Pharmacol 535:157–65

    Article  CAS  PubMed  Google Scholar 

  66. Ardid D, Alloui A, Brousse G, et al (2001) Potentiation of the antinociceptive effect of clomipramine by a 5-HT1A antagonist in neuropathic pain in rats. Br J Pharmacol 132:1118–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Marchand F, Pelissier T, Eschalier A, et al (2004) Blockade of supraspinal 5-HT1A receptors potentiates the inhibitory effect of venlafaxine on wind-up activity in mononeuropathic rats. Brain Res 1008:288–92

    Article  CAS  PubMed  Google Scholar 

  68. Micó JA, Ardid D, Berrocoso E, Eschalier A (2006) Antidepressants and pain. Trends Pharmacol Sci 27:348–54

    Article  PubMed  CAS  Google Scholar 

  69. Rojas-Corrales MO, Berrocoso E, Micó JA (2005) Role of 5-HT 1A and 5-HT1B receptors in the antinociceptive effect of tramadol. Eur J Pharmacol 511:21–6

    Article  CAS  PubMed  Google Scholar 

  70. Jeong CY, Choi JI, Yoon MH (2004) Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats. Eur J Pharmacol 502:205–11

    Article  CAS  PubMed  Google Scholar 

  71. Colpaert FC (2006) 5-HT1A receptor activation: new molecular and neuroadaptive mechanisms of pain relief. Curr Opin Investig Drugs 7:40–7

    CAS  PubMed  Google Scholar 

  72. Bardin L, Tarayre JP, Malfetes N, et al (2003) Profound, nonopioid analgesia produced by the high-efficacy 5-HT1A agonist F 13640 in the formalin model of tonic nociceptive pain. Pharmacology 67:182–94

    Article  CAS  PubMed  Google Scholar 

  73. Kiss I, Degryse AD, Bardin L, et al (2005) The novel analgesic, F 13640, produces intra- and postoperative analgesia in a rat model of surgical pain. Eur J Pharmacol 523:29–39

    Article  CAS  PubMed  Google Scholar 

  74. Colpaert FC, Tarayre JP, Koek W, et al (2002) Large-amplitude 5-HT1A receptor activation: a new mechanism of profound, central analgesia. Neuropharmacology 43:945–58

    Article  CAS  PubMed  Google Scholar 

  75. Deseure K, Koek W, Colpaert FC, Adriaensen H (2002) The 5- HT1A receptor agonist F 13640 attenuates mechanical allodynia in a rat model of trigeminal neuropathic pain. Eur J Pharmacol 456:51–7

    Article  CAS  PubMed  Google Scholar 

  76. Colpaert FC, Hamon M, Wiesenfeld-Hallin Z (2006) 5-HT1A receptors in chronic pain processing and control. In: Flor H, Kalso E, Dostrovsky JO (eds) Proceedings of the 11th World Congress on Pain. IASP Press, Seattle, pp 147–54

    Google Scholar 

  77. Alhaider AA, Wilcox GL (1993) Differential roles of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptor subtypes in modulating spinal nociceptive transmission in mice. J Pharmacol Exp Ther 265:378–85

    CAS  PubMed  Google Scholar 

  78. Liu FY, Xing GG, Qu XX, et al (2007) Roles of 5-hydroxytryptamine (5-HT) receptor subtypes in the inhibitory effects of 5-HT on C-fiber responses of spinal wide dynamic range neurons in rats. J Pharmacol Exp Ther 321:1046–53

    Article  CAS  PubMed  Google Scholar 

  79. Bonnefont J, Chapuy E, Clottes E, et al (2005) Spinal 5-HT1A receptors differentially influence nociceptive processing according to the nature of the noxious stimulus in rats: effect of WAY- 100635 on the antinociceptive activities of paracetamol, venlafaxine and 5-HT. Pain 114:482–90

    Article  CAS  PubMed  Google Scholar 

  80. Palit S, Sheaff RJ, France CR, et al (2011) Serotonin transporter gene (5-HTTLPR) polymorphisms are associated with emotional modulation of pain but not emotional modulation of spinal nociception. Biol Psychol 86:360–9

    Article  PubMed  Google Scholar 

  81. David SP, Murthy NV, Rabiner EA, et al (2005) A functional genetic variation of the serotonin (5-HT) transporter affects 5- HT1A receptor binding in humans. J Neurosci 25:2586–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Schaldemose EL, Horjales-Araujo E, Demontis D, et al (2014) No association of polymorphisms in the serotonin transporter gene with thermal pain sensation in healthy individuals. Mol Pain 10:76

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Viguier F, Michot B, Hamon M, Bourgoin S (2013) Multiple roles of serotonin in pain control mechanisms — implications of 5-HT7 and other 5-HT receptor types. Eur J Pharmacol 716:8–16

    Article  CAS  PubMed  Google Scholar 

  84. Arvieu L, Mauborgne A, Bourgoin S, et al (1996) Sumatriptan inhibits the release of CGRP and substance P from the rat spinal cord. Neuroreport 7:1973–6

    Article  CAS  PubMed  Google Scholar 

  85. Thorlund K, Mills EJ, Wu P, et al (2014) Comparative efficacy of triptans for the abortive treatment of migraine: a multiple treatment comparison meta-analysis. Cephalalgia 34:258–67

    Article  PubMed  Google Scholar 

  86. Buzzi MG, Carter WB, Shimizu T, et al (1991) Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion. Neuropharmacology 30:1193–200

    Article  CAS  PubMed  Google Scholar 

  87. Kaube H, Hoskin KL, Goadsby PJ (1993) Inhibition by sumatriptan of central trigeminal neurones only after blood-brain barrier disruption. Br J Pharmacol 109:788–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Goadsby PJ, Akerman S, Storer RJ (2001) Evidence for postjunctional serotonin (5-HT1) receptors in the trigeminocervical complex. Ann Neurol 50:804–7

    Article  CAS  PubMed  Google Scholar 

  89. Bartsch T, Knight YE, Goadsby PJ (2004) Activation of 5-HT 1B/1D receptor in the periaqueductal gray inhibits nociception. Ann Neurol 56:371–81

    Article  CAS  PubMed  Google Scholar 

  90. Skingle M, Birch PJ, Leighton GE, Humphrey PP (1990) Lack of antinociceptive activity of sumatriptan in rodents. Cephalalgia 10:207–12

    Article  CAS  PubMed  Google Scholar 

  91. Kayser V, Aubel B, Hamon M, Bourgoin S (2002) The antimigraine 5-HT1B/1D receptor agonists, sumatriptan, zolmitriptan and dihydroergotamine, attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain. Br J Pharmacol 137:1287–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Nikai T, Basbaum AI, Ahn AH (2008) Profound reduction of somatic and visceral pain by intrathecal administration of the anti-migraine drug, sumatriptan. Pain 139:533–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kayser V, Latrémolière A, Hamon M, Bourgoin S (2011) Nmethyl- D-aspartate receptor-mediated modulations of the antiallodynic effects of 5-HT1B/1D receptor stimulation in a rat model of trigeminal neuropathic pain. Eur J Pain 15:451–8

    Article  CAS  PubMed  Google Scholar 

  94. Mannoury la Cour C, El Mestikawy S, Hanoun N, et al (2006) Regional differences in the coupling of 5-hydroxytryptamine1A receptors to G proteins in the rat brain. Mol Pharmacol 70:1013–21

    Article  PubMed  CAS  Google Scholar 

  95. Tateyama M, Kubo Y (2006) Dual signaling is differentially activated by different active states of the metabotropic glutamate receptor 1alpha. Proc Natl Acad Sci USA 103:1124–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Michot B, Bourgoin S, Viguier F, et al (2012) Differential effects of CGRP receptor blockade by olcegepant on neuropathic pain in cephalic and extra-cephalic territories in the rat. Pain 153:1939–48

    Article  CAS  PubMed  Google Scholar 

  97. Michot B, Kayser V, Hamon M, Bourgoin S (2015) CGRP receptor blockade by MK-8825 alleviates allodynia in infraorbital nerve-ligated rats. Eur J Pain 19:281–90

    Article  CAS  PubMed  Google Scholar 

  98. Michaelis M, Vogel C, Blenk KH, et al (1998) Inflammatory mediators sensitize acutely axotomized nerve fibers to mechanical stimulation in rats. J Neurosci 18:7581–7

    CAS  PubMed  Google Scholar 

  99. Nakajima K, Obata H, Ito N, et al (2009) The nociceptive mechanism of 5-hydroxytryptamine released into the peripheral tissue in acute inflammatory pain in rats. Eur J Pain 13:441–7

    Article  CAS  PubMed  Google Scholar 

  100. Wei H, Chen Y, Hong Y (2005) The contribution of peripheral 5-hydroxytryptamine2A receptor to carrageenan-evoked hyperalgesia, inflammation and spinal Fos protein expression in the rat. Neuroscience 132:1073–82

    Article  CAS  PubMed  Google Scholar 

  101. Nishiyama T (2005) Effects of a 5-HT2A receptor antagonist, sarpogrelate, on thermal or inflammatory pain. Eur J Pharmacol 516:18–22

    Article  CAS  PubMed  Google Scholar 

  102. Nitanda A, Yasunami N, Tokumo K, et al (2005) Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain. Neurochem Int 47:394–400

    Article  CAS  PubMed  Google Scholar 

  103. Hashizume H, Kawakami M, Yoshida M, et al (2007) Sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, attenuates neurogenic pain induced by nucleus pulposus in rats. Spine 32:315–20

    Article  PubMed  Google Scholar 

  104. Van Steenwinckel J, Brisorgueil MJ, Fischer J, et al (2008) Role of spinal serotonin 5-HT2A receptor in 2',3'-dideoxycytidine- induced neuropathic pain in the rat and the mouse. Pain 137:66–80

    Article  PubMed  CAS  Google Scholar 

  105. Thibault K, van Steenwinckel J, Brisorgueil MJ, et al (2008) Serotonin 5-HT2A receptor involvement and Fos expression at the spinal level in vincristine-induced neuropathy in the rat. Pain 140:305–22

    Article  CAS  PubMed  Google Scholar 

  106. Cornea-Hebert V, Riad M, Wu C, et al (1999) Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat. J Comp Neurol 409:187–209

    Article  CAS  PubMed  Google Scholar 

  107. Zhang YQ, Gao X, Ji GC, Wu GC (2001) Expression of 5-HT2A receptor mRNA in rat spinal dorsal horn and some nuclei of brainstem after peripheral inflammation. Brain Res 900:146–51

    Article  CAS  PubMed  Google Scholar 

  108. Boothman L, Raley J, Denk F, et al (2006) In vivo evidence that 5-HT2C receptors inhibit 5-HT neuronal activity via a GABAergic mechanism. Br J Pharmacol 149:861–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Invernizzi RW, Pierucci M, Calcagno E, et al (2007) Selective activation of 5-HT2C receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: a combined in vivo electrophysiological and neurochemical study. Neuroscience 144:15231–5

    Article  CAS  Google Scholar 

  110. Bardin L, Lavarenne J, Eschalier A (2000) Serotonin receptor subtypes involved in the spinal antinociceptive effect of 5-HT in rats. Pain 86:11–8

    Article  CAS  PubMed  Google Scholar 

  111. Obata H, Saito S, Sakurazawa S, et al (2004) Antiallodynic effects of intrathecally administered 5-HT2C receptor agonists in rats with nerve injury. Pain 108:163–9

    Article  CAS  PubMed  Google Scholar 

  112. Obata H, Ito N, Sasaki M, et al (2007) Possible involvement of spinal noradrenergic mechanisms in the antiallodynic effect of intrathecally administered 5-HT2C receptor agonists in the rat with peripheral nerve injury. Eur J Pharmacol 567:89–94

    Article  CAS  PubMed  Google Scholar 

  113. Nakae A, Nakai K, Tanaka T, et al (2008) The role of RNA editing of the serotonin2C receptor in a rat model of oro-facial neuropathic pain. Eur J Neurosci 27:2373–9

    Article  PubMed  Google Scholar 

  114. Nakae A, Nakai K, Tanaka T, et al (2008) Serotonin2C receptor mRNA editing in neuropathic pain model. Neurosci Res 60:228–31

    Article  CAS  PubMed  Google Scholar 

  115. Zeitz KP, Guy N, Malmberg AB, et al (2002) The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci 22:1010–9

    CAS  PubMed  Google Scholar 

  116. Kia HK, Miquel MC, McKernan RM, et al (1995) Localization of 5-HT3 receptors in the rat spinal cord: immunohistochemistry and in situ hybridization. Neuroreport 6:257–61

    Article  CAS  PubMed  Google Scholar 

  117. Hamon M, Gallissot MC, Menard F, et al (1989) 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol 164:315–22

    Article  CAS  PubMed  Google Scholar 

  118. Huang J, Wang YY, Wang W, et al (2008) 5-HT3A receptor subunit is expressed in a subpopulation of GABAergic and enkephalinergic neurons in the mouse dorsal spinal cord. Neurosci Lett 441:1–6

    Article  CAS  PubMed  Google Scholar 

  119. Conte D, Legg ED, McCourt AC, et al (2005) Transmitter content, origins and connections of axons in the spinal cord that possess the serotonin (5-hydroxytryptamine)3 receptor. Neuroscience 134:165–73

    Article  CAS  PubMed  Google Scholar 

  120. Faerber L, Drechsler S, Ladenburger S, et al (2007) The neuronal 5-HT3 receptor network after 20 years of research — Evolving concepts in management of pain and inflammation. Eur J Pharmacol 560:1–8

    Article  CAS  PubMed  Google Scholar 

  121. Alhaider AA, Lei SZ, Wilcox GL (1991) Spinal 5-HT3- mediated antinociception: possible release of GABA. J Neurosci 11:1881–8

    CAS  PubMed  Google Scholar 

  122. Hayashida KI, Kimura M, Yoshizumi M, et al (2012) Ondansetron reverses anti-hypersensitivity from clonidine in rats following peripheral nerve injury: role of ?-amino butyric acid in a2- adrenoceptor and 5-HT3 serotonin receptor analgesia. Anesthesiology 117:389–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Ali Z, Wu G, Kozlov A, Barasi S (1996) The role of 5-HT3 in nociceptive processing in the rat spinal cord: results from behavioral and electrophysiological studies. Neurosci Lett 208:203–7

    Article  CAS  PubMed  Google Scholar 

  124. Guo W, Miyoshi K, Dubner R, et al (2014) Spinal 5-HT3 receptors mediate descending facilitation and contribute to behavioral hypersensitivity via a reciprocal neuron-glial signaling cascade. Mol Pain 10:35

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Donovan-Rodriguez T, Urch CE, Dickenson AH (2006) Evidence of a role for descending serotonergic facilitation in a rat model of cancer-induced bone pain. Neurosci Lett 393:237–42

    Article  CAS  PubMed  Google Scholar 

  126. Saria A, Javorsky F, Humpel C, Gamse R (1990) 5-HT3- receptor antagonists inhibit sensory neuropeptide release from the rat spinal cord. NeuroReport 1:104–6

    Article  CAS  PubMed  Google Scholar 

  127. Fukudo S, Kinoshita Y, Okumura T, et al (2016) Ramosetron reduces symptoms of irritable bowel syndrome with diarrhea and improves quality of life in women. Gastroenterology 150:358–66

    Article  CAS  PubMed  Google Scholar 

  128. Vergne-Salle P, Dufauret-Lombard C, Bonnet C, et al (2011) A randomised, double-blind, placebo-controlled trial of dolasetron, a 5-hydroxytryptamine3 receptor antagonist, in patients with fibromyalgia. Eur J Pain 15:509–14

    Article  CAS  PubMed  Google Scholar 

  129. McCleane GJ, Suzuki R, Dickenson AH (2003) Does a single intravenous injection of the 5-HT3 receptor antagonist ondansetron have an analgesic effect in neuropathic pain? A doubleblinded, placebo-controlled cross-over study. Anesth Analg 97:1474–8

    Article  CAS  PubMed  Google Scholar 

  130. Cardenas CG, Del Mar LP, Cooper BY, Scroggs RS (1997) 5- HT4 receptors couple positively to tetrodotoxin-insensitive sodium channels in a subpopulation of capsaicin-sensitive rat sensory neurons. J Neurosci 17:7181–9

    CAS  PubMed  Google Scholar 

  131. Ghelardini C, Galeotti N, Casamenti F, et al (1996) Central cholinergic antinociception induced by 5-HT4 agonists: BIMU 1 and BIMU 8. Life Sci 58:2297–309

    Article  CAS  PubMed  Google Scholar 

  132. Bianchi C, Rodi D, Marino S, et al (2002) Dual effects of 5-HT4 receptor activation on GABA release from guinea pig hippocampal slices. Neuroreport 13:2177–80

    Article  CAS  PubMed  Google Scholar 

  133. Hammerle CW, Surawicz CM (2008) Updates on treatment of irritable bowel syndrome. World J Gastroenterol 14:2639–49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Sengupta JN, Mickle A, Kannampalli P, et al (2014) Visceral analgesic effect of 5-HT4 receptor agonist in rats involves the rostroventral medulla (RVM). Neuropharmacology 79:345–58

    Article  CAS  PubMed  Google Scholar 

  135. Doly S, Fischer J, Brisorgueil MJ, et al (2004) 5-HT5A receptor localization in the rat spinal cord suggests a role in nociception and control of pelvic floor musculature. J Comp Neurol 476:316–29

    Article  CAS  PubMed  Google Scholar 

  136. Liu XY, Wu SX, Wang YY, et al (2005) Changes of 5-HT receptor subtype mRNAs in rat dorsal root ganglion by bee venom-induced inflammatory pain. Neurosci Lett 375:42–6

    Article  CAS  PubMed  Google Scholar 

  137. Vidal-Cantu GC, Jiménez-Hernàndez M, Rocha-Gonzàlez HI, et al (2016) Role of 5-HT5A and 5-HT1B/1D receptors in the antinociception produced by ergotamine and valerenic acid in the rat formalin test. Eur J Pharmacol 781:109–16

    Article  CAS  PubMed  Google Scholar 

  138. Xu WJ, Zhao Y, Huo FQ, et al (2013) Involvement of ventrolateral orbital cortex 5-HT1-7 receptors in 5-HT-induced depression of spared nerve injury allodynia. Neuroscience 238:252–7

    Article  CAS  PubMed  Google Scholar 

  139. Gérard C, Martres MP, Lefevre K, et al (1997) Immunolocalization of serotonin 5-HT6 receptor-like material in the rat central nervous system. Brain Res 746:207–19

    Article  PubMed  Google Scholar 

  140. Castaneda-Corral G, Rocha-Gonzalez HI, Araiza-Saldana CI, et al (2009). Role of peripheral and spinal 5-HT6 receptors according to the rat formalin test. Neuroscience 162:444–52

    Article  CAS  PubMed  Google Scholar 

  141. Finn DP, Fone KC, Beckett SR, et al (2007) The effects of pharmacological blockade of the 5-HT6 receptor on formalin-evoked nociceptive behaviour, locomotor activity and hypothalamopituitary-adrenal axis activity in rats. Eur J Pharmacol 569: 59–63

  142. Devegowda VN, Hong JR, Cho S, et al (2013) Synthesis and the 5-HT6 receptor antagonistic effect of 3-arylsulfonylamino- 5,6-dihydro-6-substituted pyrazolo[3,4]pyridinones for neuropathic pain treatment. Bioorg Med Chem Lett 23:4696–700

    Article  CAS  PubMed  Google Scholar 

  143. Jayarajan P, Nirogi R, Shinde A, et al (2015) 5-HT6 receptor antagonist attenuates the memory deficits associated with neuropathic pain and improves the efficacy of gabapentinoids. Pharmacol Rep 67:934–42

    Article  CAS  PubMed  Google Scholar 

  144. Meuser T, Pietruck C, Gabrie A, et al (2002) 5-HT7 receptors are involved in mediating 5-HT-induced activation of rat primary afferent neurons. Life Sci 71:2279–89

    Article  CAS  PubMed  Google Scholar 

  145. Doly S, Fischer J, Brisorgueil MJ, et al (2005) Pre- and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal cord: immunocytochemical evidence. J Comp Neurol 490:256–69

    Article  CAS  PubMed  Google Scholar 

  146. Neumaier JF, Sexton TJ, Yracheta J, et al (2001) Localization of 5-HT7 receptors in rat brain by immunocytochemistry, in situ hybridization, and agonist stimulated cFos expression. J Chem Neuroanat 21:63–73

    Article  CAS  PubMed  Google Scholar 

  147. Martin-Cora FJ, Pazos A (2004) Autoradiographic distribution of 5-HT7 receptors in the human brain using [3H]mesulergine: comparison to other mammalian species. Br J Pharmacol 141:92–104

    Article  CAS  PubMed  Google Scholar 

  148. Rocha-González HI, Meneses A, Carlton SM, Granados-Soto V (2005) Pronociceptive role of peripheral and spinal 5-HT7 receptors in the formalin test. Pain 117:182–92

    Article  PubMed  CAS  Google Scholar 

  149. Amaya-Castellanos E, Pineda-Farias JB, Castaneda-Corral G, et al (2011) Blockade of 5-HT7 receptors reduces tactile allodynia in the rat. Pharmacol Biochem Behav 99:591–7

    Article  CAS  PubMed  Google Scholar 

  150. Viguier F, Michot B, Kayser V, et al (2012) GABA, but not opioids, mediates the anti-hyperalgesic effects of 5-HT7 receptor activation in rats suffering from neuropathic pain. Neuropharmacology 63:1093–110

    Article  CAS  PubMed  Google Scholar 

  151. Martínez-García E, Leopoldo M, Lacivita E, Terrón JA (2011) Increase of capsaicin-induced trigeminal Fos-like immunoreactivity by 5-HT7 receptors. Headache 51:1511–9

    Article  PubMed  Google Scholar 

  152. Dogrul A, Seyrek M (2006) Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors, in the spinal cord. Br J Pharmacol 149:498–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Yanarates O, Dogrul A, Yildirim V, et al (2010) Spinal 5-HT7 receptors play an important role in the antinociceptive and antihyperalgesic effects of tramadol and its metabolite, Odesmethyltramadol, via activation of descending serotonergic pathways. Anesthesiology 112:696–710

    Article  CAS  PubMed  Google Scholar 

  154. Seyrek M, Kahraman S, Deveci MS, et al (2010) Systemic cannabinoids produce CB1-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT 7 and 5-HT2A receptors. Eur J Pharmacol 649:183–94

    Article  CAS  PubMed  Google Scholar 

  155. Brenchat A, Romero L, Torrens A, et al (2009) 5-HT7 receptor activation inhibits mechanical allodynia secondary to capsaicin sensitization in mice. Pain 141:239–47

    Article  CAS  PubMed  Google Scholar 

  156. Krobert KA, Andressen KW, Levy FO (2006) Heterologous desensitization is evoked by both agonist and antagonist stimulation of the human 5-HT7 serotonin receptor. Eur J Pharmacol 532:1–10

    Article  CAS  PubMed  Google Scholar 

  157. Brenchat A, Nadal X, Romero L, et al (2010) Pharmacological activation of 5-HT7 receptors reduces nerve injury-induced mechanical and thermal hypersensitivity. Pain 149:483–94

    Article  CAS  PubMed  Google Scholar 

  158. Viguier F, Kayser V, Hamon M, Bourgoin S (2012) 5-HT7 receptor-mediated modulation of nociceptive primary afferent fibers involves GABAA receptors, Cl–transport dynamics and T-type Ca2+ channels. In: 14th World Congress of Pain. IASP, Milan, August

    Google Scholar 

  159. Kawamata T, Omote K, Toriyabe M, et al (2002) Intracerebroventricular morphine produces antinociception by evoking gamma-aminobutyric acid release through activation of 5- hydroxytryptamine3 receptors in the spinal cord. Anesthesiology 96:1175–82

    Article  CAS  PubMed  Google Scholar 

  160. Nozaki C, Kamei J (2006) Possible involvement of opioidergic systems in the antinociceptive effect of the selective serotonin reuptake inhibitors in sciatic nerve injured mice. Eur J Pharmacol 552:99–104

    Article  CAS  PubMed  Google Scholar 

  161. Akerman S, Romero-Reyes M, Holland PR (2016) Current and novel insights into the neurophysiology of migraine and its implications for therapeutics. Pharmacol Ther doi: 10.1016/j. pharmathera.2016.12.005

  162. Yokogawa F, Kiuchi Y, Ishikawa Y, et al (2002) An investigation of monoamine receptors involved in antinociceptive effects of antidepressants. Anesth Analg 95:163–8

    Article  CAS  PubMed  Google Scholar 

  163. Khouzam HR (2016) Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics. Postgrad Med 128:323–30

    Article  PubMed  Google Scholar 

  164. Zhang D, Blanco MJ, Ying BP, et al (2015) Discovery of selective N-[3-(1-methyl-piperidine-4-carbonyl)-phenyl]- benzamide-based 5-HT1F receptor agonists: evolution from byclic to monocyclic cores. Bioorg Med Chem Lett 25: 4337–41

  165. Reuter U, Israel H, Neeb L (2015) The pharmacological profile and clinical prospects of the oral 5-HT1F receptor agonist lasmiditan in the acute treatment of migraine. Ther Adv Neurol Disord 8:46–54

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Ohashi-Doi K, Himaki D, Nagao K, et al (2010) A selective, high affinity 5-HT2B receptor antagonist inhibits visceral hypersensitivity in rats. Neurogastroenterol Motil 22:e69–e76

    Article  CAS  PubMed  Google Scholar 

  167. Cervantes-Duran C, Vidal-Cantu GC, Barragan-Iglesias P, et al (2012) Role of peripheral and spinal 5-HT2B receptors in formalin-induced nociception. Pharmacol Biochem Behav 102:30–5

    Article  CAS  PubMed  Google Scholar 

  168. Su YS, Chiu YY, Lin SY, et al (2016) Serotonin receptor 2B mediates mechanical hyperalgesia by regulating transient receptor potential vanilloid 1. J Mol Neurosci 59:113–25

    Article  CAS  PubMed  Google Scholar 

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  1. Inserm UMR 894, centre de psychiatrie et neurosciences, 2 ter, rue d’Alésia, F-75014, Paris, France

    S. Bourgoin, A. Gautier & M. Hamon

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  1. S. Bourgoin
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  2. A. Gautier
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Bourgoin, S., Gautier, A. & Hamon, M. Le yin et le yang de la sérotonine : un Janus dans les contrôles de la douleur. Douleur analg 30, 35–56 (2017). https://doi.org/10.1007/s11724-017-0486-3

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