Neuronal nicotinic receptors as targets for novel analgesics

The potential use of nicotinic acetylcholine receptor agonists has been the subject of a number of recent reviews. Despite the promises of better things to come, few new compounds have been identified that circumvent the issues hindering the widespread use of the previously described nicotinic analgesics, mainly a narrow therapeutic window between analgesic efficacy and toxicity, and a lack of knowledge of native nicotinic acetylcholine receptor expression. However, several recent developments have potentially opened new windows of opportunity in the use of nicotinic agents for analgesia. A small number of laboratories have reported that peripheral nerve injury alters the pharmacology of nicotinic receptors, resulting in a leftward shift of analgesic potency but not of toxicity. Another important development in the pathophysiology of neuropathic pain is the reliance of nerve injury-induced behavioural hypersensitivity on both peripheral and central neural immune interactions. Finally, the reported neuroprotective effects of nicotine following spinal cord injury may provide an opportunity for the development of selective nicotinic agonists that are capable of attenuating chronic pain. The current review will attempt to highlight these recent developments and outline key findings that demonstrate further opportunity for the development of nicotinic agonists as novel analgesics.