Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron

Abstract

Objectives: To test the analgesic effect of 5-HT-3 receptor antagonist, tropisetron, in a clip compression injury model of spinal cord pain in rats. Methods: Four weeks post compression of the spinal cord at lumbar level, tropisetron was administered intrathecally at 100 μg and 150 μg dosages. Behavioral tests were assessed before administration. Fifteen minutes after injection, behavioral tests were repeated. Randall-Sellitto and plantar test was used for mechanical and thermal hyperalgesia, respectively. Mechanical and cold allodynia were evaluated by Von Frey filament and acetone droplets, respectively. The analgesic effect of tropisetron was compared with intrathecal administration of salicylate. Locomotor score was evaluated by Basso, Beattie and Bresnahan (BBB) test every week after spinal cord injury. Results: Intrathecal administration of tropisetron, decreased hyperalgesia and mechanical allodynia, but not cold allodynia were observed after compression of the spinal cord. Conclusion: Blockade of 5-HT-3 receptors by tropisetron at the spinal level induces an antinociceptive effect on chronic central neuropathic pain and suggests that this compound may have potential clinical utility for the management of central neuropathic pain, particularly in patients with hyperalgesia and tactile allodynia.

Rostral ventromedial medulla‐mediated descending facilitation following P2X7 receptor activation is involved in the development of chronic post‐operative pain

“…; Nasirinezhad et al . ). This shift from antinociception to pronociception may be mediated by the enhanced activation of 5‐HT receptor subtypes, which are pronociceptive, for example, the 5‐HT3R (Ali et al .…”

“…At least half of the RVM neurons projecting to the spinal cord contain 5-HT (Skagerberg and Bjorklund 1985;Jones and Light 1992). These neurons were initially considered to have antinociceptive effects and later pronociceptive effects (Bourgoin et al 1980;Rivot et al 1982;Song et al 1999;Nasirinezhad et al 2016). This shift from antinociception to pronociception may be mediated by the enhanced activation of 5-HT receptor subtypes, which are pronociceptive, for example, the 5-HT3R (Ali et al 1996;Zeitz et al 2002;Guo et al 2014).…”

Protective effects of tropisetron on cerulein-induced acute pancreatitis in mice

“…In a randomized clinical trial, Mei et al reported that a single-dose intravenous administration of tropisetron significantly alleviates early postoperative pain in women undergoing gynecological laparoscopies compared with those receiving placebo [43]. Likewise, Intrathecal administration of tropisetron in rats with spinal cord injury, decreased hyperalgesia and mechanical allodynia [44].…”

Neural stem/progenitor cell transplantation for spinal cord injury treatment; A systematic review and meta-analysis

“…Pharmacotherapy holds the base of current treatment with little influence on functional recovery with only 30-40% decrease in neuropathic pain symptoms (Finnerup et al, 2005;Backonja et al, 2006). Besides, numerous medication adverse side effects are the major obstacles for the long-term use (Marineo et al, 2012;Hosseini et al, 2014;Nasirinezhad et al, 2015a). Motor dysfunction and neuropathic pain will persist unless the injured region recovers or pain control pathways reinforce.…”