Nerve injury-induced changes in opioid modulation of wide dynamic range dorsal column nuclei neurones

Abstract

In the present study we investigated the effects of spinal morphine on the electrically and naturally evoked responses of gracile nuclei neurones in a rat model of neuropathy, induced by the tight ligation of lumbar L5/6 spinal nerves. Two weeks after surgery, animals were prepared for electrophysiological recordings and neuronal responses were characterised to a range of controlled natural (brush, low- and high-intensity von Frey filaments, heat 45°C) and peripheral electrical stimuli. Morphine (0.1, 0.25, 1 and 5 μg) was applied spinally and its effect was compared to that in sham-operated or naive animals. Following surgery, all neuropathic rats exhibited signs of mechanical allodynia. Nerve injury induced a significant increase in the receptive field size of gracile nuclei neurones, and also produced a non-significant increase in the proportion and level of spontaneous activity in these neurones. The baseline electrical and natural evoked responses remained unaltered. Spinal morphine reduced both the Aδ-fibre- and C-fibre-evoked responses of gracile nuclei neurones, and similarly inhibited the heat-evoked responses of neuropathic, sham-operated and naive rats. Morphine, however, produced only minor reductions (<30% inhibition of pre-drug control responses) of the Aβ-fibre- and brush-evoked responses of gracile nuclei neurones. These drug effects were similar in all animal groups. In complete contrast, morphine produced a marked inhibition of the low-intensity punctate mechanical evoked responses (von Freys 2 and 9 g) after nerve injury, an effect that was totally lacking in the sham-operated or naive animal groups. This dramatic shift was selective for the low-intensity punctate mechanical stimuli and such an effect was not seen with the noxious mechanical punctate stimulus (von Frey 75 g) where there was a modest inhibition in all groups. Our results suggest that there is plasticity in the opioid modulation of dorsal column projection pathways following spinal nerve ligation and these alterations appear to interact with sensory pathways conveying low-threshold punctate stimuli.