Involvement of spinal muscarinic and serotonergic receptors in the anti-allodynic effect of electroacupuncture in rats with oxaliplatin-induced neuropathic pain

Involvement of spinal muscarinic and serotonergic receptors in the anti-allodynic effect of electroacupuncture in rats with oxaliplatin-induced neuropathic pain

This study was performed to investigate whether the spinal cho-linergic and serotonergic analgesic systems mediate the relieving effect of elec-troacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat’s tail into cold water (4^oC) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of M₂(methoctramine, 10μg) and M₃(4-DAMP, 10μg) receptor antagonist, but not M₁(pirenzepine, 10μg) receptor antagonist, blocked the effect. Also, spinal administration of 5-HT₃(MDL-72222, 12μg) receptor antagonist, but not 5-HT_1A (NAN-190, 15μg) or 5-HT_2A(ketanserin, 30μg) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a signì cant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic (M₂, M₃) and serotonergic (5-HT₃) receptors.