Targeting the α9α10 nicotinic acetylcholine receptor to treat severe pain

The alpha(9)alpha(10) nicotinic acetylcholine receptors (nAChRs) are recognized for their function in the hair cells of the inner ear; transcripts for alpha(9) and/or alpha(10) subunits have also been identified in a diverse range of other tissues, including immune cells. The functioning of alpha(9)alpha(10) nAChRs in these latter tissues is unknown. However, a recent series of studies has provided evidence that blockade of the alpha(9)alpha(10) nAChR can alleviate chronic pain resulting from overt peripheral nerve injury or inflammation and increase the functional recovery of damaged neurons. Systemic administration of alpha(9)alpha(10) 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 alpha(9)alpha(10) nAChRs reduces the number of immune cells present at the site of injury.