BIPHASIC MODULATION OF SPINAL NOCICEPTIVE TRANSMISSION FROM THE MEDULLARY RAPHE NUCLEI IN THE RAT

The modulatory effects of electrical and chemical (glutamate) stimulat ion in the rostral ventromedial medulla (RVM) on spinal nociceptive tr ansmission and a spinal nociceptive reflex were studied in rats. Elect rical stimulation at a total 86 sites in the RVM in the medial raphe n uclei (n = 54) and adjacent gigantocellular areas (n = 32) produced bi phasic (facilitatory and inhibitory, n = 43) or only inhibitory (n = 4 3) modulation of the tail-flick (TF) reflex. At these 43 biphasic site s in the RVM, facilitation of the TF reflex was produced at low intens ities of stimulation (5-25 mu A) and inhibition was produced at greate r intensities of stimulation (50-200 mu A). At 43 sites in the RVM, el ectrical stimulation only produced intensity-dependent inhibition of t he TF reflex. Activation of cell bodies in the RVM by glutamate microi njection reproduced the biphasic modulatory effects of electrical stim ulation. At biphasic sites previously characterized by electrical stim ulation, glutamate at a low concentration (5 nmol) produced facilitati on of the TF reflex; a greater concentration (50 nmol) only inhibited the TF reflex. In electrophysiological experiments, electrical stimula tion at 62 sites in the RVM produced biphasic (n = 26), only inhibitor y (n = 26), or only facilitatory (n = 10) modulation of responses of l umbar spinal dorsal horn neurons to noxious cutaneous thermal (50 degr ees C) or mechanical (75.9 g) stimulation. Facilitatory effects were p roduced at lesser intensities of stimulation and inhibitory effects we re produced at greater intensities of stimulation. The apparent latenc ies to stimulation-produced facilitation and inhibition, determined wi th the use of a cumulative sum method and bin-by-bin analysis of spina l neuron responses to noxious thermal stimulation of the skin, were 23 1 and 90 ms, respectively. The spinal pathways conveying descending fa cilitatory and inhibitory influences were found to be different. Desce nding facilitatory influences on the TF reflex were conveyed in ventra l/ventrolateral funiculi, whereas inhibitory influences were conveyed in dorsolateral funiculi. The results indicate that descending inhibit ory and facilitatory influences can be simultaneously engaged througho ut the RVM, including nucleus raphe mag nus, and that such influences are conveyed in different spinal funiculi.