Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens

The nucleus accumbens, as part of the mesolimbic dopaminergic reward pathwa y, mediates both addiction to and withdrawal from substances of abuse. In a ddition, activity of substances of abuse such as opioids in the nucleus acc umbens has been implicated in pain modulation. Because nucleus accumbens ni cotinic receptors are important in nicotine addiction and because nicotinic activity can interact with opioid action, we investigated the contribution of nucleus accumbens nicotinic receptors to opioid-mediated analgesia/anti nociception. The response of the nociceptive jaw-opening reflex to opioids was studied in the rat, both before and during chronic nicotine exposure. I n nicotine-naive rats, intra-accumbens injection of the nicotinic receptor antagonist mecamylamine blocked antinociception produced by either systemic morphine, intra-accumbens co-administration of a mu- and a delta -opioid r eceptor agonist, or noxious stimulation (i.e., subdermal capsaicin in the h indpaw); intra-accumbens mecamylamine alone had no effect. The antinocicept ive effect of either morphine or noxious stimulation was unchanged during n icotine tolerance; however, intra-accumbens mecamylamine lost its ability t o block antinociception produced by either treatment. Intra-accumbens mecam wylamine by itself precipitated significant hyperalgesia in nicotine-tolera nt rats which could be suppressed by noxious stimulation as well as by morp hine. These results indicate that nucleus accumbens nicotinic receptors play an i mportant role in both opioid- and noxious stimulus-induced antinociception in nicotine-naive rats. This role was attenuated in the nicotine-dependent state. The suppression of withdrawal hyperalgesia by noxious stimulation su ggests that pain can ameliorate the symptoms of withdrawal, thus suggesting a possible mechanism for pain-seeking behavior. (C) 2001 IBRO. Published b y Elsevier Science Ltd. All rights reserved.