Reduction in opioid and non-opioid forms of swim analgesia by 5-HT2 receptor antagonists.

Acute exposure to continuous (CCWS) or intermittent (ICWS) cold-water swims elicits non-opioid and opioid forms of analgesia respectively. Intrathecal administration of methysergide blocks ICWS, but not CCWS analgesia. The present study evaluated the role of serotonin (5-HT) receptor subtypes in the mediation of CCWS and ICWS analgesia on the tail-flick and jump tests following administration of methysergide, a non-specific 5-HT antagonist and pirenpirone and ketanserin, two 5-HT2 receptor subtype antagonists. Systemic methysergide was more effective in reducing CCWS analgesia (50-58%, 0.1-1.0 mg/kg) than ICWS analgesia (21%, 5 mg/kg) on both pain tests. Systemic pirenpirone (0.04-0.2 mg/kg) and ketanserin (1-5 mg/kg) were also more effective in reducing CCWS analgesia (43-57%) on both tests than ICWS analgesia (pirenpirone: 0.4 mg/kg, 34%; ketanserin: 5 mg/kg, 21%) on the tail-flick test. Indeed, both 5-HT2 receptor antagonists potentiated ICWS analgesia on the jump test. While serotonin antagonist effects upon hypothermia could not account for CCWS analgesia effects, similar potentiations in ICWS analgesia and hypothermia were observed following pirenpirone and ketanserin. Finally, both 5-HT2 receptor antagonists differentially reduced CCWS hypothermia and potentiated ICWS hypothermia. These data suggest differential serotonergic modulation of the two forms of swim analgesia with opioid-mediated ICWS analgesia acting through spinal 5-HT1 receptors and non-opioid-mediated CCWS analgesia acting through supraspinal 5-HT2 receptors.