Quantitative characterization of ceruleospinal inhibition of nociceptive transmission in the rat.

Abstract

A total of 51 dorsal horn units responsive to heat were isolated and their receptive fields characterized (i.e., response properties and adequate stimuli determined) in pentobarbital-anesthetized, paralyzed rats. In 39 of the 51 units, the descending inhibition of heat-evoked activity produced by focal electrical stimulation in the locus ceruleus/subceruleus (LC/SC) was examined. All units studied responded to mechanical stimulation, to electrical stimulation of the ipsilateral tibial nerve at intensities supramaximal to activate A-alpha, delta- and C-fibers, and to noxious heating (50 degrees C) of the footpad. The cutaneous receptive fields of all units were confined to the glabrous skin of the toes and footpad. All neurons examined were located in the dorsal horn of the spinal cord in laminae I-VI. Tracking experiments established that inhibition of heat-evoked dorsal horn unit activity could be reliably produced by focal electrical stimulation in both the contralateral and ipsilateral LC/SC. The inhibition produced by electrical stimulation in the LC/SC was intensity-, pulse duration-, and frequency-dependent. In six experiments, the efficacy of LC/SC stimulation-produced inhibition of heat-evoked activity was compared using two pulse durations (100 and 400 microseconds); greater inhibition of heat-evoked activity was produced at lower intensities of stimulation at the 400-microseconds pulse duration. In 10 experiments, the frequency of stimulation was varied (25-200 Hz); stimulation at a frequency of 100 Hz resulted in maximal inhibition of heat-evoked activity for stimulation sites both inside (n = 7) and outside (n = 3) the LC/SC. Inhibition of heat-evoked dorsal horn unit activity could be reliably produced by focal electrical stimulation in sites inside the LC/SC (n = 18). Significant descending inhibition of noxious heat-evoked spinal neuronal activity could also be produced by stimulation in pontine sites located outside the LC/SC, however, not as reliably. Systematic electrode tracks were made through the pons, using a searching stimulus of 100 microA, to locate sites medial, lateral, and ventral to the LC/SC from which significant descending inhibition could be produced. Stimulation in 156 sites outside the LC/SC at 100 microA produced inhibition of heat-evoked spinal unit activity to 50% of control or less in only 37 sites. Descending inhibition was characterized quantitatively from 14 of these 37 sites; the mean intensities of stimulation to inhibit heat-evoked activity to 50% of control were experimentally determined, and the mean thresholds of stimulation for inhibition and the mean recruitment indices were calculated.(ABSTRACT TRUNCATED AT 400 WORDS)