Effects of neonatal capsaicin treatment on descending modulation of spinal nociception from the rostral, medial medulla in adult rat

Abstract Stimulation-produced modulation from the rostral, medial medulla (RMM) on the spinal nociceptive tail-flick (TF) reflex and on lumbar spinal dorsal horn neuron reponses to noxious cutaneous stimulti was studied in adult rats treated as neonates with capsaicin or vehicle. In vehicle-treated rats ( n = 7), both descending facilitatory and inhibitory influences on the TF reflex were produced from the RMM. At 11/23 sites in the RMM, electrical stimulation produced biphasic modulatory effects. Electrical stimulation facilitated the spinal nociceptive TF reflex at low intensities (5–25 μA) and inhibited the TF reflex at greater intensities (50–200 μA). The mean threshold intensity of stimulation to inhibit the TF reflex (cut-off time= 7.0s) was 66 μA ( n = 11). At 11 of 23 sites, electrical stimulation only inhibited the TF reflex; the mean threshold intensity of stimulation to inhibit the TF reflex was 50 μA ( n = 11). At one stimulation site, electrical stimulation only facilitated the TF reflex at the intensities tested (5–100 μA). In capsaicin-treated rats ( n = 6), the proportion of sites from which electrical stimulation only inhibited the TF reflex was significantly less (3/27sites= 11%) than in vehicle-treated rats (11/23= 48%). The threshold intensity of stimulation to inhibit the TF reflex from these three sites was 50 μA. The number of sites RMM fronm which electrical stimulation only facilitated the TF reflex was significantly greater in capaicin-treated rats (15/27= 56%) than in vehicle-treated 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 significantly differed between vehicle- and capsaicin-treated rats. In electrophysiological experiments, all units studied responded to non-noxious and noxious intensities of mechanical stimulation applied to the glabrous skin of the plantar surface of the ipsilateral hind foot and also to noxious heating of the skin (50°C). The number of sites where electrical stimulation produced only facilitatory effects on responses of spinal dorsal horn neurons to noxious stimulation (thermal or mechanical) of the skin was significantly increased from 13% of the total 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 decreased from 47% of the total sites in vehicle-treated rats to 35% in capsaicin-treated rats. The intensity of stimulation for producing inhibitory effects and the magnitude of inhibitory effects produced were not significantly different between vehicle- and capsaicin-treated rats. Immunocytochemical evaluation of the lumbar spinal dorsal horn verified that there were substantial reductions in substance-P and calcitonin gene-related peptide-like immunoreactivity, confirming the effectiveness of neonatal capsaicin treatment. The present study, in support of anatomical studies documenting central effects of capsaicin, suggests that neonatal capsaicin treatment also has significant effects on bulbospinal systems important to the modulation of spinal nociceptive transmission. 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.