title: Morphine and somatostatin analogue reduce c-fos expression in trigeminal subnucleus caudalis produced by corneal stimulation in the rat.
abstract: The influence of morphine and somatostatin on nociceptor-evoked activation of central trigeminal neurons and cardiovascular reflex responses was assessed in barbiturate-anaesthetized rats. Morphine or the somatostatin analogue, octreotide, was given intracerebroventricularly 20 min prior to application of mustard oil to the corneal surface. The expression of the immediate early gene, c-fos, was used to estimate neuronal activation within the spinal trigeminal nucleus. Morphine reduced the number of Fos-positive neurons produced at the transition region between trigeminal subnucleus caudalis and the upper cervical spinal cord, whereas c-fos expression at the subnucleus interpolaris/caudalis transition was not affected significantly. Morphine also reduced the arterial pressure and heart rate responses to corneal stimulation in proportion to the dose of morphine and required a threshold dose similar to that which reduced c-fos expression. Naloxone prevented the morphine-induced inhibition of c-fos expression and cardiovascular reflex responses to corneal stimulation. Somatostatin analogue reduced the number of Fos-positive neurons at the subnucleus caudalis/cervical cord transition, but not at the subnucleus interpolaris/caudalis transition, an 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. Intracerebroventricular administration of morphine and somatostatin analogue inhibit corneal activation of neurons within the superficial laminae at the subnucleus caudalis/cervical cord transition through opioid and non-opioid-dependent neural pathways, respectively. By contrast, the low sensitivity of corneal-responsive neurons at the subnucleus interpolaris/caudalis transition to analgesics suggests that these neurons are not simply a rostral extension of the medullary dorsal horn. Correlation analyses suggest that morphine-induced inhibition of cardiovascular responses to corneal stimulation depend on the activity of neurons at the subnucleus caudalis/cervical cord transition and not on those at the subnucleus interpolaris/caudalis transition region.
authors.affiliation: Department of Neuroscience, Brown University/Rhode Island Hospital, Providence 02903, U.S.A.
authors.forename: D A
authors.initials: DA
authors.lastname: Bereiter
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003315:Cornea / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D007839:Functional Laterality; D016762:Genes, fos / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009149:Mustard Plant; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils; D010946:Plants, Medicinal; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000502:physiology*
chemical_list: D010936:Plant Extracts; D010938:Plant Oils; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D009020:Morphine; D015282:Octreotide; C027793:mustard oil