Targeting the alpha9alpha10 nicotinic acetylcholine receptor to treat severe pain.

The alpha9alpha10 nicotinic acetylcholine receptors (nAChRs) are recognized for their function in the hair cells of the inner ear; transcripts for a9 and/or a10 subunits have also been identified in a diverse range of other tissues , including immune cells. The functioning of alpha9alpha10 nAChRs in these latter tissues is unknown. However, a recent series of studies has provided evidence that blockade of the alpha9alpha10 nAChR can alleviate chronic pain resulting from overt peripheral nerve injury or inflammation and increase the functional recovery of damaged neurons. Systemic administration of alpha9alpha10 antagonists produces an acute analgesia; repeated daily administrations produces sustained and cumulative levels of analgesia across 7 days without the development of tolerance. Although the exact mechanism of action is unknown, antagonism of the alpha9alpha10 nAChRs reduces the number of immune cells present at the site of injury.