Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: Mediation by spinal adrenergic and serotonergic receptors

The present study was performed to examine the effects of electroacupuncture (EA) on cold allodynia and its mechanisms related to the spinal adrenergic and serotonergic systems in a rat model of neuropathic pain. For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, EA stimulation (2 or 100 Hz) was delivered to Zusanli (ST36) for 30 min. The behavioral signs of cold allodynia were evaluated by the tail immersion test [i.e., immersing the tail in cold water (4°C) and measuring the latency to an abrupt tail movement] before and after the stimulation. And then, we examined the effects of intrathecal injection of prazosin (α₁-adrenoceptor antagonist, 30 μg), yohimbine (α₂-adrenoceptor antagonist, 30 μg), NAN-190 (5-HT _1A antagonist, 15 μg), ketanserin (5-HT_2A antagonist, 30 μg), and MDL-72222 (5-HT₃ antagonist, 12 μg) on the action of EA stimulation. Although both 2 Hz and 100 Hz EA significantly relieved the cold allodynia signs, 2 Hz EA induced more robust effects than 100 Hz EA. In addition, intrathecal injection of yohimbine, NAN-190, and MDL-72222, but not prazosin and ketanserin, significantly blocked the relieving effects of 2 Hz EA on cold allodynia. These results suggest that low-frequency (2 Hz) EA is more suitable for the treatment of cold allodynia than high-frequency (100 Hz) EA, and spinal α₂-adrenergic, 5-HT_1A and 5-HT ₃, but not α₁-adrenergic and 5-HT_2A, receptors play important roles in mediating the relieving effects of 2 Hz EA on cold allodynia in neuropathic rats.