Correlation of noxious evoked c-fos expression in areas of the somatosensory system during chronic pain: involvement of spino-medullary and intra-medullary connections.

Chronic pain induces functional alterations of the endogenous pain control system namely in the modulation of nociceptive transmission at the spinal cord. We used the c-fos expression as a tool to study correlated neuronal activation, induced by bending the inflamed paw of monoarthritic animals, between the spinal dorsal horn and medullary centers belonging to the endogenous pain control system, namely the lateralmost reticular formation of the ventrolateral medulla (VLMlat), the lateral reticular nucleus (LRt), the dorsal reticular nucleus (DRt), the nucleus tractus solitarius (Sol) and the rostroventromedial medulla (RVM). Awake monoarthritic rats were subjected to 4 min of paw bending followed by anaesthesia and perfusion either immediately or 2h later. The numbers of Fos immunoreactive neurons in the spinal dorsal horn and in the medulla oblongata were significantly correlated mainly immediately after stimulation: lamina I correlated with the VLMlat, LRt, Sol and RVM; lamina II correlated with the VLMlat, LRt and Sol; and laminae IV-V correlated with the VLMlat and LRt. Between medullary pain control centers significant correlations occurred immediately and 2h after bending at the VLMlat-Sol and LRt-Sol, at the VLMlat-LRt and VLMlat-RVM in animals perfused immediately, and at the VLMlat-DRt and LRt-RVM in animals perfused 2h later. These data demonstrate that the mobilization of a chronically inflamed paw triggers intense correlated neuronal activity in several areas of the somatosensory system, indicating functional relevant links in pain control.