title: Spinal 5-HT3AR contributes to BmK I-induced inflammatory pain in rats.
abstract: Subcutaneous injection of BmK I could be adopted to well establish a novel pain model. Moreover, 5-hydroxytryptamine (serotonin, 5-HT) receptor is involved in regulating animal pain-related behaviors. However, the underlying mechanism of 5-HT3R on BmK I-induced pain remains unclear. Animal behavioral testing, RT-PCR and Western blotting were used to yield the following results: first, intraplantar (i.pl.) injection of BmK I (10 μg) induced elevated mRNA and protein levels of 5-HT3AR in bilateral L4-L5 spinal cord; Second, intrathecal (i.t.) injection of ondansetron (a specific antagonist of 5-HT3AR) reduced spontaneous pain responses, attenuated unilateral thermal and bilateral mechanical hypersensitivity elicited by BmK I; Microglia could be activated by BmK I (i.pl.) in both sides of L4-L5 spinal cord, and this effect was reversed by intrathecal pre-treatment with 5-HT3AR antagonist. Meanwhile, the 5-HT3AR in L4-L5 spinal cord was almost co-localized with NeuN (a marker of nerve cell), but not co-expressed with Iba-1 (a marker of microglia). Finally, the expression level of CX3CL1 and CX3CR1 was reduced by intrathecal pre-treatment with ondansetron. Our results indicate that both 5-HT3AR signaling pathway and microglia are activated in the process of induction and maintenance of BmK I-induced pain nociception. Meanwhile, our results suggest that the neuronal 5-HT3AR may communicate with microglia indirectly via CX3CL1 which is involved in regulating the BmK I-induced hyperalgesia and sensitization.
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China.
authors.forename: Yun-Lu
authors.initials: YL
authors.lastname: Jiao
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China.
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Li
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China. yhji@staff.shu.edu.cn.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Ji
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D054428:Chemokine CX3CL1 / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced*; D007249:Inflammation / Q000503:physiopathology*; D007278:Injections, Spinal; D017628:Microglia / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012604:Scorpion Venoms / Q000009:adverse effects*; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
chemical_list: D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D044406:Receptors, Serotonin, 5-HT3; D012604:Scorpion Venoms; C105338:makatoxin I