Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation

Previous findings indicate that the brain stem descending system becomes mo re active in modulating spinal nociceptive processes during the development of persistent pain. The present study further identified the supraspinal s ites that mediate enhanced descending modulation of behavior hyperalgesia a nd dorsal horn hyperexcitability (as measured by Fos-like immunoreactivity) produced by subcutaneous complete Freund's adjuvant (CFA). Selective chemi cal lesions were produced in the nucleus raphe magnus (NRM), the nuclei ret icularis gigantocellularis (NGC), or the locus coeruleus/subcoeruleus (LC/S C). Compared to vehicle-injected animals with injection of vehicle alone, m icroinjection of a serotoninergic neurotoxin 5,7-dihydroxytryptamine into t he NRM significantly increased thermal hyperalgesia and Fos protein express ion in lumbar spinal cord after hindpaw inflammation. In contrast, the sele ctive bilateral destruction of the NGC with a soma-selective excitotoxic ne urotoxin, ibotenic acid, led to an attenuation of hyperalgesia and a reduct ion of inflammation-induced spinal Fos expression. Furthermore, if the NGC lesion was extended to involve the NRM, the behavioral hyperalgesia and CFA -induced Fos expression were similar to that in vehicle-injected rats. Bila teral LC/SC lesions were produced by microinjections of a noradrenergic neu rotoxin, DSP-4. There was a significant increase in inflammation-induced sp inal Fos expression, especially in the ipsilateral superficial dorsal horn following LC/SC lesions. These results demonstrated that multiple specific brain stem sites are involved in descending modulation of inflammatory hype ralgesia. Both NRM and LC/SC descending pathways are major sources of enhan ced inhibitory modulation in inflamed animals. The persistent hyperalgesia and neuronal hyperexcitability may be mediated in part by a descending pain facilitatory system involving NGC. Thus, the intensity of perceived pain a nd hyperalgesia is fine-tuned by descending pathways. The imbalance of thes e modulating systems may be one mechanism underlying variability in acute a nd chronic pain conditions. (C) 1999 International Association for the Stud y of Pain. Published by Elsevier Science B.V.