The long term goal of this research project is to characterize spinal cord spatial and temporal neural mechanisms that encode information related to acute and chronic pain. Progress during the last 3 years of this project has resulted in evidence that both spatial recruitment and impulse frequencies in spinal nociceptive neurons are likely to be critical factors in encoding nociceptive stimulus intensity as well as in encoding the distinction between non-nociceptive and nociceptive somatosensory events. The proposed continuation of these efforts will rely on the utilization of [14C]-2-deoxyglucose mapping procedures and electrophysiological recordings from dorsal horn nociceptive neurons to accomplish 7 SpecifiC aims: (1) To provide electrophysiological mapping of L2 to L5 neural activity under stimulus conditions used in the [14C]-2- deoxyglucose experiments so as to provide functional interpretations of our results with metabolic imaging analysis; (2) To more precisely delineate the rostral-caudal extent of elevated neural activity elicited by graded nociceptive thermal stimuli; (3) To determine the similarities and differences in the rat spinal cord of spatial patterns of elevated neural activity in response to nociceptive stimulation in spinalized, decerebrate, and intact preparations; (4) To determine how spatial recruitment and/or integration at the level of single spinal cord nociceptive neurons Can account for spatial summation of heat induced pain; (5) To compare the patterns of [14C]-2-deoxyglucose activity within the spinal cord across two types of nociceptive stimuli: thermal stimulation (45 degrees-49 degrees C) and formalin injection into the foot and to relate such patterns of activity with areas of spinal gray matter (at cervical levels and contralateral dorsal horn regions) known to be either inhibited or excited by the types of stimuli to be used ; (6) To further examine the spatial patterns of elevated neural activity in the spinal cords of rats experiencing experimental painful peripheral mononeuropathy and to compare such patterns with electrophysiological recordings of neural activity from L2 to L5; (7) To examine the effects of antagonists of the glutamate/aspartate receptor and local anesthetic agents on behavioral indexes of pain and spatial distributions of elevated neural activity within spinal cords of rats with a painful mononeuropathy. The results of this proposed work will provide an extensive characterization of the role of spatial and temporal factors in encoding nociceptive information under both acute and pathophysiological conditions. Finally, the analysis of pharmacological interventions on spatial recruitment and on abnormal pain-related behavior in a model of neuropathic pain may be helpful in providing new therapeutic approaches to treat neuropathic pain and perhaps other chronic pain disorders in man.
