The analgesic effect of electroacupuncture on inflammatory pain in the rat model of collagenase-induced arthritis: mediation by opioidergic receptors

Electroacupuncture (EA) is widely practiced for the treatment of osteoarthritic (OA) pain, but its therapeutic mechanisms have not yet been fully studied, especially in the experimental OA rat model. In order to induce collagenase-induced arthritis (CIA) in rats, male Sprague-Dawley rats were intra-articularly injected with 0.05 ml of 4 mg/ml collagenase solution in the left knee of the hind limb, followed by a booster injection 4 days later. Maximal gross, histopathological features and biomarker activity changes consistent with human OA characteristics were observed four weeks after the first collagenase injection. In the exploratory preliminary study of EA stimulation parameters, low-frequency train pulse EA stimulation (2 Hz, 0.07 mA, 0.3 ms) delivered to the Zusanli (ST36) acupoint exerted an antinociceptive effect with acupoint specificity in a rat model of CIA. The antinociceptive effect of Zusanli EA was blocked by intraperitoneal pretreatment with naloxone (mu-opioid receptor antagonist, 2 mg/kg) and naltrindole (delta-opioid receptor antagonist, 1 mg/kg), but not with norbinaltophimine (kappa-opioid receptor antagonist, 20 mg/kg). The synergistic antinociceptive effects of Zusanli EA were achieved with statistical significance by i.p. pretreatment with DAMGO (mu-opioid receptor agonist, 1 mg/kg) and with [D-Ala2]-Deltorphin II (delta-opioid receptor agonist, 6 mg/kg), but not with (+/-)-U-50488 (kappa-opioid receptor agonist, 3 mg/kg). These results suggest that the 2-Hz EA can attenuate the osteoarthritic pain in CIA, and the analgesic effects of EA can be mediated by mu-opioid and delta-opioid, but not by kappa-opioid receptors.