Differential opioid inhibition of C- and A delta- fiber mediated thermonociception after stimulation of the nucleus raphe magnus.

Abstract

Although the importance of the nucleus raphe magnus in descending inhibitory control of nociception is clear, it is not known whether these effects are equivalent for different types of nociception. Thus, we examined the differential inhibition of behavioral responses evoked by A delta or C fiber thermonociceptor activation by electrical stimulation of nucleus raphe magnus neurons as well as the involvement of different classes of opiate receptors in this inhibition. In general, it was necessary to apply twice as much current to the nucleus raphe magnus to produce criterion antinociception for A delta mediated versus C fiber mediated nociceptive responses. Intrathecal administration of the nonselective opioid receptor antagonist, naltrexone, or the delta(1) opioid receptor antagonist, naltrindole, attenuated both A delta and C fiber antinociception induced by nucleus raphe magnus stimulation with similar efficacy. In contrast, intrathecal administration of naloxonazine, a micro specific opioid receptor antagonist, or naltriben, a delta(2) specific opioid receptor antagonist, preferentially attenuated nucleus raphe magnus induced antinociception for C fiber responses when compared with A delta mediated responses. These findings suggest that nociception evoked by the activation of A delta or C fiber nociceptors is under pharmacologically distinguishable descending control from the nucleus raphe magnus. Opiates differentially inhibit pain produced by the activation of myelinated or unmyelinated pain sensing neurons, a distinction that is clinically important. This article demonstrates that the brain's own pain control system operates with similar selectivity, and that this selectivity is partly mediated by different opiate receptor subtypes.