Analgesic effect of interferon-alpha via mu opioid receptor in the rat

Using the tail-flick induced by electro-stimulation as a pain marker, it wa s found that pain threshold (PT) was significantly increased after injectin g interferon-alpha (IFN alpha) into the lateral ventricle of rats. This eff ect was dosage-dependent and abolished by monoclonal antibody (McAb) to IFN alpha. Naloxone could inhibit the analgesic effect of IFN alpha, suggestin g that the analgesic effect of IFN alpha be related to the opioid receptors . beta-funaltrexamine (beta-FNA), the mu specific receptor antagonist could completely block the analgesic effect of IFN alpha. The selective delta-op ioid receptor antagonist, ICI174,864 and the kappa-opioid receptor antagoni st, nor-BNI both failed to prevent the analgesic effect of IFN alpha. IFN a lpha could significantly inhibit the production of the cAMP stimulated by f orskolin in SK-N-SH cells expressing the mu-opioid receptor, not in NG108-1 5 cells expressing the delta-opioid receptor uniformly. The results obtaine d provide further evidence for opioid activity of IFN alpha and suggest tha t this effect is mediated by central opioid receptors of the mu subtype. Th e evidence is consistent with the hypothesis that multiple actions of cytok ines, such as immunoregulatory and neuroregulatory effects, might be mediat ed by distinct domains of cytokines interacting with different receptors. ( C) 2000 Elsevier Science Ltd. All rights reserved.