Nicotinic Acetylcholine Receptors Mediate the Suppressive Effect of an Injection of Diluted Bee Venom into the GV3 Acupoint on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats.
Oxaliplatin, a platinum-based chemotherapy drug, often induces acute neuropathic pain, especially cold allodynia, even after a single administration. Subcutaneous injection of diluted bee venom (BV) into acupoints has been used to treat various pain symptoms in traditional oriental medicine. Although we previously demonstrated the suppressive effect of BV injection on oxaliplatin-induced cold allodynia in rats, its neurochemical mechanism remained unclear. This study investigates whether and how the cholinergic system mediates the relieving effect of BV injection on cold allodynia in oxaliplatin-administered rats. The behavioral signs of cold allodynia induced by an oxaliplatin administration (6 mg/kg, intraperitoneally (i.p.)) were evaluated by a tail immersion test in cold water (4°C). BV (0.25 mg/kg, subcutaneously (s.c.)) injection into the Yaoyangguan acupoint, located between the spinous processes of the fourth and fifth lumbar vertebrae, significantly alleviated the cold allodynia. This relieving effect of BV injection on oxaliplatin-induced cold allodynia was blocked by a pretreatment with mecamylamine (a non-selective nicotinic receptor antagonist, 2 mg/kg, i.p.), but not by atropine (a non-selective muscarinic receptor antagonist, 1 mg/kg, i.p.). Further, dihydro-β-erythroidinehydrobromide (DHβE, an α4β2 nicotinic antagonist, 5 mg/kg, i.p.) prevented the anti-allodynic effect of BV, whereas methyllycaconitine (an α7 nicotinic antagonist, 6 mg/kg, i.p.) did not. Finally, intrathecal administration of DHβE (10 nM) blocked the BV-induced anti-allodynic effect. These results suggest that nicotinic acetylcholine receptors, especially spinal α4β2 receptors, but not muscarinic receptors, mediate the suppressive effect of BV injection on oxaliplatin-induced acute cold allodynia in rats.
Department of Physiology, College of Korean Medicine, Kyung Hee University.
Heera
H
Yoon
Min Joon
MJ
Kim
Insoo
I
Yoon
Dong Xing
DX
Li
Hyunsu
H
Bae
Sun Kwang
SK
Kim
D015669:Acupuncture Points; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D056705:Apitherapy; D001514:Bee Venoms / Q000627:therapeutic use*; D003080:Cold Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007267:Injections; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000009:adverse effects*; D000077150:Oxaliplatin; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism
D000970:Antineoplastic Agents; D001514:Bee Venoms; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D009944:Organoplatinum Compounds; D011978:Receptors, Nicotinic; D000077150:Oxaliplatin