Selective opioid inhibition of small nociceptive neurons.

Opioid analgesia, the selective suppression of pain without effects on other sensations, also distinguishes between different types of pain: severe, persistent pain is potently inhibited by opioids, but they fail to cohceal the sensation of a pinprick. The cellular basis for this specificity was analyzed by means of patch-clamp experiments performed on fluorescently labeled nociceptive neurons (nociceptors) that innervate rat tooth pulp. Activation of the mu opioid receptor inhibited calcium channels on almost all small nociceptors but had minimal effect on large nociceptors. Somatostatin had the opposite specificity, preferentially inhibiting calcium channels on the large cells. Because persistent pain is mediated by slow-conducting, small nociceptors, opioids are thus likely to inhibit neurotransmitter release only at those primary synapses specialized for persistent pain.