title: Antinociceptive effect of peripheral serotonin 5-HT2B receptor activation on neuropathic pain.
abstract: Serotonin is critically involved in neuropathic pain. However, its role is far from being understood owing to the number of cellular targets and receptor subtypes involved. In a rat model of neuropathic pain evoked by chronic constriction injury (CCI) of the sciatic nerve, we studied the role of 5-HT(2B) receptor in dorsal root ganglia (DRG) and the sciatic nerve. We showed that 5-HT(2B) receptor activation both prevents and reduces CCI-induced allodynia. Intrathecal administration of 5-HT(2B) receptor agonist BW723C86 significantly attenuated established mechanical and cold allodynia; this effect was prevented by co-injection of RS127445, a selective 5-HT(2B) receptor antagonist. A single application of BW723C86 on the sciatic nerve concomitantly to CCI dose-dependently prevented mechanical allodynia and significantly reduced cold allodynia 17 days after CCI. This behavioral effect was accompanied with a marked decrease in macrophage infiltration into the sciatic nerve and, in the DRG, with an attenuated abnormal expression of several markers associated with local neuroinflammation and neuropathic pain. CCI resulted in a marked upregulation of 5-HT(2B) receptor expression in sciatic nerve and DRG. In the latter structure, it was biphasic, consisting of a transient early increase (23-fold), 2 days after the surgery and before the neuropathic pain emergence, followed by a steady (5-fold) increase, that remained constant until pain disappeared. In DRG and sciatic nerve, 5-HT(2B) receptors were immunolocalized on sensory neurons and infiltrating macrophages. Our data reveal a relationship between serotonin, immunocytes, and neuropathic pain development, and demonstrate a critical role of 5-HT(2B) receptors in blood-derived macrophages.
authors.affiliation: Université Pierre et Marie Curie (UPMC), Site Pitié-Salpêtrière, INSERM UMRS 975, CNRS 7225, Centre de Recherche de l'ICM, Paris 75013, France Université Pierre et Marie Curie (UPMC), INSERM U839, Institut du Fer à Moulin, Paris, France.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Urtikova
authors.forename: Nadège
authors.initials: N
authors.lastname: Berson
authors.forename: Juliette
authors.initials: J
authors.lastname: Van Steenwinckel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Doly
authors.forename: Jérémy
authors.initials: J
authors.lastname: Truchetto
authors.forename: Luc
authors.initials: L
authors.lastname: Maroteaux
authors.forename: Michel
authors.initials: M
authors.lastname: Pohl
authors.forename: Marie
authors.initials: M
authors.lastname: Conrath
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000502:physiology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B / Q000235:genetics / Q000378:metabolism*; D012584:Sciatic Nerve / Q000502:physiology; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D007211:Indoles; D044403:Receptor, Serotonin, 5-HT2B; D058826:Serotonin 5-HT2 Receptor Agonists; D013876:Thiophenes; D012701:Serotonin