<b>Electrophysiological evidence for the involvement of facilitation of descending pain inhibitory system in the antinociceptive action of neurotropin </b>

Abstract

Neurotropin®, a non protein extract from inflamed rabbit skin inoculated with vaccinia virus, is well known as an analgesic for chronic pain such as low back pain and postherpetic neuralgia, etc. In previous behavioral studies, we have shown that neurotropin activates the monoaminergic descending pain inhibitory system. In the present study, we examined the effects of neurotropin on serotonergic neurons in the nucleus raphe magnus (NRM, the origin of serotonergic descending pain inhibitory neuron) in the rostroventromedial medulla using whole-cell patch-clamp technique in brainstem slices. In some instances, recorded neurons were identified as NRM neurons with neurobiotin filled in the recording pipettes. NRM neurons had a resting membrane potential of about -60 mV. Bath application of neurotropin (1.0 NU/mL) depolarized NRM neurons, and it resulted in initiating an action potential under current-clamp conditions. Under voltage-clamp conditions at a holding potential of -70 mV, NRM neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs). Neurotropin (0.2 - 1.0 NU/mL) did not change the frequency and amplitude of spontaneous EPSCs. However, neurotropin dose-dependently induced an inward current in approximately 60% of NRM neurons tested. The neurotropin-induced inward current was observed even in the presence of tetrodotoxin (1 µM). The reversal potential for the current was close to 0 mV, indicating that the neurotropin-induced current is mediated by the activation of non-selective cation channels. Neurotropin produced an inward current, in all neurons immunohistochemically stained for tryptophan hydroxylase (TPH), a marker for serotonergic neuron. These results indicate that neurotropin directly excites serotonergic NRM neurons without affecting the excitatory synaptic inputs to NRM neurons. This facilitatory action of neurotropin on serotonergic NRM neurons may have an important role for the neurotropin-induced analgesia.