Spinal 5-HT₃ receptor contributes to somatic hyperalgesia induced by sub-chronic stress

Abstract

Stress facilitates pain perception and sensitizes pain pathways, but the underlying mechanism is still unclear. The purpose of this study was to investigate whether the activation of 5-hydroxytryptamine (5-HT) subtype-3 receptor in the spinal cord contributes to somatic hyperalgesia induced by repeated three-day forced swim in the estradiol replacement rats after ovariectomy. Somatic sensitivity was assessed by thermal withdrawal latency to radiant heat and mechanical withdrawal threshold to von Frey filaments. The expression of 5-HT 3A receptor in the L4–L5 dorsal spinal cord was examined by Western blot. Repeated forced swim stress reduced the thermal withdrawal latency and mechanical withdrawal threshold, and the presence of estradiol exaggerated this hyperalgesia. The expression of 5-HT 3A receptor in the L4–L5 dorsal spinal cord increased significantly following repeated forced swim in estradiol replacement rats. Intrathecal injection of 5-HT 3 receptor antagonist Y-25130 blocked the somatic hyperalgesia induced by forced swim stress. These data indicate that 5-HT 3 receptor activation through the descending facilitation system contributes to the somatic hyperalgesia evoked by forced swim stress. The results may provide a new therapeutic avenue for alleviating pain induced by stress.

The Role of Descending Pain Modulation in Chronic Primary Pain: Potential Application of Drugs Targeting Serotonergic System

“…Our recent studies also provided evidence for 5-HT 3 receptors involved in somatic pain, an obvious symptom of FMS [127]. Specifically, we established an FMS model with three-day forced swim stress in female rats and investigated the role of the spinal 5-HT 3 receptors in somatic pain induced by stress [127]. We found that the expression of 5-HT 3 receptors in L4-5 spinal dorsal horn upregulated with the occurrence of pain and blocking 5-HT 3 receptors by intrathecal administration of Y25130 reversed this process, providing a possible mechanism of 5-HT 3 receptor antagonists applied in chronic pain without local tissue pathology [127].…”

“…5-HT 3 receptor antagonists dolasetron and tropisetron have been assessed for efficacy in FMS patients [125,126]. Our recent studies also provided evidence for 5-HT 3 receptors involved in somatic pain, an obvious symptom of FMS [127]. Specifically, we established an FMS model with three-day forced swim stress in female rats and investigated the role of the spinal 5-HT 3 receptors in somatic pain induced by stress [127].…”

“…Specifically, we established an FMS model with three-day forced swim stress in female rats and investigated the role of the spinal 5-HT 3 receptors in somatic pain induced by stress [127]. We found that the expression of 5-HT 3 receptors in L4-5 spinal dorsal horn upregulated with the occurrence of pain and blocking 5-HT 3 receptors by intrathecal administration of Y25130 reversed this process, providing a possible mechanism of 5-HT 3 receptor antagonists applied in chronic pain without local tissue pathology [127]. As 5-HT 3 receptor antagonists are rapidly absorbed and easily penetrate the blood-brain barrier [128], these drugs may control pain in IBS, TMD, and FMS through the central mechanisms combined with their peripheral functions, leading to a hypothesis that 5-HT 3 receptor antagonists can be candidate drugs in chronic pain management of patients with CPP.…”

Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation

“…The NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV, 30 nmol in 10 μl, Sigma, St. Louis, MO, USA) or 5-HT 3 receptor antagonist Y-25130 (30 fmol in 10 ul, Tocris, Bioscience, Bristol, UK ) was then administered at 30 min before CFA injection and each FS. The doses of drugs were determined by previous studies [ 13 , 14 ] and our preliminary experiments. Intrathecal injection of saline was used for vehicle control.…”

Preclinical models of deep craniofacial nociception and temporomandibular disorder pain

“…Currently, interpretation of immobility behaviors as depression-like behaviors is controversial [ 179 , 180 ]; however, FS is the useful model for studying the basis for stress-induced hyperalgesia, since FS (10–20 min/day) could consistently increase nociceptive responses in the animals. For example, FS for 2–3 days causes hyperalgesia in the hindpaw, increased neural activities in the lumbar dorsal horn [ 181 , 182 ] and in the supra-spinal areas [ 183 , 184 ].…”