Spinal 5-HT3AR contributes to BmK I-induced inflammatory pain in rats.
- Author:
Jin FU
1
;
Yun-Lu JIAO
1
;
Zheng-Wei LI
1
;
Yong-Hua JI
2
Author Information
1. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China.
2. Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200444, China. yhji@staff.shu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Behavior, Animal;
Chemokine CX3CL1;
metabolism;
Hyperalgesia;
chemically induced;
Inflammation;
physiopathology;
Injections, Spinal;
Microglia;
drug effects;
Rats;
Rats, Sprague-Dawley;
Receptors, Serotonin, 5-HT3;
metabolism;
Scorpion Venoms;
adverse effects;
Spinal Cord;
metabolism;
physiopathology
- From:
Acta Physiologica Sinica
2015;67(3):283-294
- CountryChina
- Language:English
-
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.
