EFFECTS OF NEONATAL CAPSAICIN TREATMENT ON DESCENDING MODULATION OF SPINAL NOCICEPTION FROM THE ROSTRAL, MEDIAL MEDULLA IN ADULT-RAT

Stimulation-produced modulation from the rostral, medial medulla (RMM) on the spinal nociceptive tail-flick (TF) reflex and on lumbar spinal dorsal horn neuron responses to noxious cutaneous stimuli was studied in adult rats treated as neonates with capsaicin or vehicle. In vehic le-treated rats (n = 7), both descending facilitatory and inhibitory i nfluences on the TF reflex were produced from the RMM. At 11/23 sites in the RMM, electrical stimulation produced biphasic modulatory effect s. Electrical stimulation facilitated the spinal nociceptive TF reflex at low intensities (5-25 mu A) and inhibited the TF reflex at greater intensities (50-200 mu A). The mean threshold intensity of stimulatio n to inhibit the TF reflex (cut-off time = 7.0 s) was 66 alpha A (n = 11). At 11 of 23 sites, electrical stimulation only inhibited the TF r eflex; the mean threshold intensity of stimulation to inhibit the TF r eflex was 50 mu A (n = 11). At one stimulation site, electrical stimul ation only facilitated the TF reflex at the intensities tested (5-100 mu A). In capsaicin-treated rats (n = 6), the proportion of sites from which electrical stimulation only inhibited the TF reflex was signifi cantly less (3/27 sites = 11%) than in vehicle-treated rats (11/23 = 4 8%). The threshold intensity of stimulation to inhibit the TF reflex f rom these three sites was 50 mu A. The number of sites in RMM from whi ch electrical stimulation only facilitated the TF reflex was significa ntly greater in capsaicin-treated rats (15/27 = 56%) than in vehicle-t reated rats (1/23 = 4%). Neither the number of sites in RMM from which electrical stimulation produced biphasic modulatory effects on the TF reflex (48% and 33%, respectively) nor the intensities of stimulation or magnitudes of facilitation or inhibition of the TF reflex signific antly differed between vehicle- and capsaicin-treated rats. In electro physiological experiments, all units studied responded to non-noxious and noxious intensities of mechanical stimulation applied to the glabr ous skin of the plantar surface of the ipsilateral hind foot and also to noxious heating of the skin (50 degrees C). The number of sites whe re electrical stimulation produced only facilitatory effects on respon ses of spinal dorsal horn neurons to noxious stimulation (thermal or m echanical) of the skin was significantly increased from 13% of the tot al sites in vehicle-treated rats to 40% in capsaicin-treated rats. The number of sites where stimulation only produced inhibitory effects on responses of spinal dorsal horn neurons to noxious stimulation was de creased from 47% of the total sites in vehicle-treated rats to 35% in capsaicin-treated rats. The intensity of stimulation for producing inh ibitory effects and the magnitude of inhibitory effects produced were not significantly different between vehicle- and capsaicin-treated rat s. Immunocytochemical evaluation of the lumbar spinal dorsal horn veri fied that there were substantial reductions in substance-P and calcito nin gene-related peptide-like immunoreactivity, confirming the effecti veness of neonatal capsaicin treatment. The present study, in support of anatomical studies documenting central effects of capsaicin, sugges ts that neonatal capsaicin treatment also has significant effects on b ulbospinal systems important to the modulation of spinal nociceptive t ransmission. Specifically, capsaicin treatment of neonates leads to a reduction in inhibitory and an increase in facilitatory influences on spinal nociception descending from the caudal brainstem.