Analgesic effect of intrathecally administered nociceptin, an opioid receptor-like 1 receptor agonist, in the rat formalin test

Abstract

Nociceptin (a heptadecapeptide also known as orphanin FQ) is a potent endogenous agonist of the opioid receptor-like 1 receptor and has a sequence similar to dynorphin A. It has been reported that intracerebroventricularly injected nociceptin produced hyperalgesia in mice and that intrathecal injection of nociceptin inhibits the spinal sensitization. In the present study, we investigated the effect of intrathecally administered nociceptin in the rat formalin test (a model of inflammatory pain) and the rat hot plate test. In the formalin test, drugs were administered 10 min before (pre-treatment study) or 7 min after (post-treatment study) the formalin injection. The paw formalin injection induces a biphasic flinching (phase 1, 0–7 min; phase 2, 10–60 min) of the injected paw. In the pre-treatment study, intrathecally administered nociceptin depressed both the phase 1 and phase 2 flinching behaviour in a dose-dependent manner, and, in the post-treatment study, intrathecal injection of nociceptin depressed the phase 2 flinching behaviour. In the pre-treatment study, the potency of nociceptin in depressing the phase 1 response was the same as that in depressing the phase 2 response. These effects of nociceptin were not antagonized by the co-administration of naloxone. Intrathecal injection of nociceptin had no effect on the hot plate test. These data suggest that nociceptin plays an important role in spinal nociceptive transmission through the activation of a naloxone-insensitive receptor, and spinally administered nociceptin produces an analgesic effect during the rat formalin test, but not the hot plate test.