DIMINISHED INFLAMMATION AND NOCICEPTIVE PAIN WITH PRESERVATION OF NEUROPATHIC PAIN IN MICE WITH A TARGETED MUTATION OF THE TYPE-I REGULATORY SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE

To assess the contribution of PKA to injury-induced inflammation and p ain, we evaluated nociceptive responses in mice that carry a null muta tion in the gene that encodes the neuronal-specific isoform of the typ e I regulatory subunit (RI beta) of PKA. Acute pain indices did not di ffer in the RI beta PKA mutant mice compared with wild-type controls. However, tissue injury-evoked persistent pain behavior, inflammation o f the hindpaw, and ipsilateral dorsal horn Fos immunoreactivity was si gnificantly reduced in the mutant mice, as was plasma extravasation in duced by intradermal injection of capsaicin into the paw. The enhanced thermal sensitivity observed in wild-type mice after intraplantar or intrathecal (spinal) administration of prostaglandin E-2 was also redu ced in mutant mice. In contrast, indices of pain behavior produced by nerve injury were not altered in the mutant mice. Thus, RI beta PKA is necessary for the full expression of tissue injury-evoked (nociceptiv e) pain but is not required for nerve injury-evoked (neuropathic) pain . Because the RI beta subunit is only present in the nervous system, i ncluding small diameter trkA receptor-positive dorsal root ganglion ce lls, we suggest that in inflammatory conditions, RI beta PKA is specif ically required for nociceptive processing in the terminals of small-d iameter primary afferent fibers.