MORPHINE AND SOMATOSTATIN ANALOG REDUCE C-FOS EXPRESSION IN TRIGEMINAL SUBNUCLEUS CAUDALIS PRODUCED BY CORNEAL STIMULATION IN THE RAT

The influence of morphine and somatostatin on nociceptor-evoked activa tion of central trigeminal neurons and cardiovascular reflex responses was assessed in barbiturate-anaesthetized rats. Morphine or the somat ostatin analogue, octreotide, was given intracerebroventricularly 20 m in prior to application of mustard oil to the corneal surface. The exp ression of the immediate early gene, c-Sos, was used to estimate neuro nal activation within the spinal trigeminal nucleus. Morphine reduced the number of Fos-positive neurons produced at the transition region b etween trigeminal subnucleus caudalis and the upper cervical spinal co rd. whereas c-fos expression at the subnucleus interpolaris/caudalis t ransition was not affected significantly. Morphine also reduced the ar terial pressure and heart rate responses to corneal stimulation in pro portion to the dose of morphine and required a threshold dose similar to that which reduced c-fos expression. Naloxone prevented the morphin e-induced inhibition of c-fos expression and cardiovascular reflex res ponses to corneal stimulation. Somatostatin analogue reduced the numbe r of Fos-positive neurons at the subnucleus caudalis/cervical cord tra nsition, but nut at the subnucleus interpolaris/caudalis transition, a n effect that was not prevented by naloxone. Somatostatin analogue did not blunt the cardiovascular responses evoked by corneal stimulation. A subthreshold dose of morphine plus a threshold dose of somatostatin analogue caused a greater inhibition of Fos-positive: neurons at the subnucleus caudalis/cervical cord transition, but not in reflex-evoked autonomic responses, than the same dose of either drug alone. Intrace rebroventricular administration of morphine and somatostatin analogue inhibit corneal activation of neurons within the superficial laminae a t the subnucleus caudalis/cervical cord transition through opioid and non-opioid-dependent neural pathways, respectively. By contrast, the l ow sensitivity of corneal-responsive neurons at the subnucleus interpo laris/caudalis transition to analgesics suggests that these neurons ar e not simply a rostral extension of the the medullary dorsal born. Cor relation analyses suggest that morphine-induced inhibition of cardiova scular responses to corneal stimulation depend on the activity of neur ons at the subnucleus caudalis/cervical cord transition and not on tho se at the subnucleus interpolaris/caudalis transition region. (C) 1997 IBRO.