GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model.

Peripheral hypersensitivities develop in the face and hindpaws of mice with nitroglycerin (NTG)-induced migraine. We evaluated whether diluted bee venom (DBV) injections at acupoints prevented these peripheral hypersensitivities and c-Fos expression in the trigeminal nucleus caudalis (TNC). NTG (10 mg/kg, intraperitoneal, i.p.) was administered every other day for nine days. DBV (0.1 mg/kg) was subcutaneously injected into the ST36 (Zusanli), LI4 (Hegu), or GV16 (Fengfu) acupoints 75 min after each NTG injection. Mice were pretreated with naloxone (5 mg/kg, i.p.) or yohimbine (5 mg/kg, i.p.) 30 min before the DBV injections. NTG injection caused facial cold allodynia, hindpaw mechanical allodynia, and increased c-Fos-immunoreactive (ir) cells in the TNC. Repetitive DBV injections at GV16, but not the ST36, or LI4 acupoints, suppressed NTG-induced hindpaw mechanical allodynia and facial cold allodynia. The number of c-Fos-ir cells also decreased in response to DBV injections at the GV16 acupoint. Remarkably, pretreatment with yohimbine reversed the anti-allodynic effects of DBV injections and attenuated the decreased c-Fos expression in response to GV16 DBV treatment. Naloxone did not block the effects of GV16 DBV stimulation. These findings demonstrate that repetitive DBV treatment at the GV16 acupoint relieves NTG-induced facial and hindpaw hypersensitivities and decreases in c-Fos expression in the TNC via activation of the alpha-2 adrenoceptors, but not the opioid receptors.