Quantitative characterization and spinal pathway mediating inhibition of spinal nociceptive transmission from the lateral reticular nucleus in the rat

A. J. Janss and G. F. Gebhart Department of Pharmacology, College of Medicine, University of Iowa City, Iowa 52242. 1. The modulation of spinal nociceptive transmission from the lateral reticular nucleus (LRN) was characterized for 47 spinal dorsal horn neurons in pentobarbital-anesthetized, paralyzed rats. All 47 units studied had receptive fields confined to the glabrous skin of the plantar surface of the ipsilateral hind foot and responded to mechanical stimulation as well as noxious heating (50 degrees C). Rostral projections contained in the ventrolateral quadrant of the cervical spinal cord were demonstrated for 15 of the 47 units by antidromic invasion. Glutamate- and stimulation-produced descending inhibition, the spinal pathway, and tonic descending inhibition from the LRN were systematically examined. 2. Inhibition of unit responses to heating of the skin by electrical stimulation in the LRN varied with the intensity, pulse duration (100 or 400 microseconds), and frequency (25-100 Hz) of stimulation. Greater inhibition was produced at lower intensities of stimulation with the 400-microseconds pulse duration and a frequency of 100 Hz. The effects of stimulation on spontaneous activity and responses to heat were compared in 16 experiments; inhibition of spontaneous activity was intensity dependent and did not differ significantly in magnitude from stimulation-produced inhibition of responses to heating of the skin. 3. Tracking experiments established that stimulation in the ipsilateral and contralateral ventrolateral medulla reliably attenuated unit responses to noxious heating of the skin and that stimulation in the LRN produced maximal inhibition at a low intensity of stimulation. Descending inhibition was quantitatively characterized from sites within (n = 32) and outside (n = 30) the LRN. Both the extrapolated mean stimulation threshold for inhibition and mean intensity inhibiting unit responses to heat to 50% of control were significantly lower for sites in the LRN. 4. The responses of seven spinal units to graded noxious heating of the skin were studied; all exhibited linear monotonic stimulus-response functions (SRFs) throughout the temperature range examined (42-50 degrees C). Electrical stimulation in the LRN significantly decreased the slope (42 +/- 4% of control) of the SRFs and increased the neuronal response threshold (2.0 +/- 0.7 degrees C). 5. S-glutamate (50 nmol, 0.5 microliter) was microinjected into stimulation sites within (n =