Interactions of 5-HT2 receptor agonists with acetylcholine in spinal analgesic mechanisms in rats with neuropathic pain

Serotonin type 2 (5-HT2) receptors reportedly inhibit neuropathic pain in the spinal cord, but little is known about how spinal 5-HT2 receptors might act against such abnormal sensitivity. We examined whether the cholinergic and tachykinin systems were involved in the antiallodynic effect of intrathecally administered 5-HT2 receptor agonists in rats with nerve injury. Allodynia was produced by tight ligation of the left L5 and L6 spinal nerves, and determined by applying von Frey hairs to the left hindpaw. Effects of intrathecal pretreatment with 5-HT2 receptor antagonists (ketanserin and RS-102221), muscarinic receptor antagonists (atropine and scopolamine), a choline uptake blocker (hemicholium-3), and an NK1 receptor antagonist (L-706336) were assessed in rats subsequently given a 100-mug intrathecal dose of a 5-HT2 receptor agonist either alpha-methyl-5-HT or iododimethoxy aminopropane (DOI). Antiallodynic effects of 5-HT2 receptor agonists were attenuated by the 5-HT2A receptor antagonist ketanserin (30 mug), but not by the 5-HT2C receptor antagonist RS-102221 (40 mug). Muscarinic receptor antagonists (30 mug each), the choline uptake blocker (10 mug), and the NK1 receptor antagonist (30 mug) also inhibited the antiallodynic effects of 5-HT2 receptor agonists. Antiallodynic effects of intrathecally administered 5-HT2 receptor agonists may be mediated by spinal release of acetylcholine induced via 5-HT2A and NK1 receptors. (C) 2003 Elsevier Science B.V. All rights reserved.