Role of 5-HT5A receptors in activation of astroglia in the spinal dorsal horn in a rat model of neuropathic pain by vincristine

Objective To evaluate the role of 5-HT5A receptors (5-HT5A R) in activation of astroglia in the spinal dorsal horn in a rat model of neuropathic pain induced by vincristine. Methods Forty adult male SD rats weighing 180-200 g were randomly divided into 4 groups ( n = 10 each): control group (group C);neuropathic pain group (group P);Ad-X-HK group (group B) and Ad-5-HT5A-siRNA group (group S). Neuropathic pain was induced by repeated intraperitoneal (IP) injection of vincristine 0.1 mg/kg according to the method described by Weng et al in group P, B and S. On the 2nd day after the last IP injection, the animals received artificial cerebrospinal fluid, Ad-X-HK and Ad-5-HT5A-siRNA 25 μl administered intrathecally (IT) in group P, B and S respectively. Paw withdrawal threshold to mechanical stimulus was measured before and on the 7th day after IT administration. The animals were then sacrificed. The lumbar segment ( L4.5 ) of the spinal cord was removed for determination of 5-HT5A R and GFAP expression. Results Body weight and paw withdrawal threshold were significantly decreased after repeated IP vincristine administration in group P compared with group C. IT Ad-5-HT5A-siRNA reduced pain threshold further in group S compared with group P. Repeated IP vincristine significantly increased the expression of 5-HT5A R and GFAP in spinal dorsal horn, and IT Ad-5-HT5A-siRNA significantly decreased the expression of 5-HT5A R while increased the expression of GFAP in spinal dorsal horn in group S compared with group P. Conclusion 5-HT5AR is involved in the inhibition of astrocyte activation, resulting in reduction of vincristineinduced neuropathic pain. Key words: Receptors, Serotonin; Astrocytes; Neuralgia; Vincristine