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.