diprenorphine and Nerve-Degeneration

We studied changes in opioid receptors (mu, delta, kappa) concentrations during temporary middle cerebral artery occlusion (MCAO) in cats by sequential displacement of unselective opioid antagonist, [3H]-diprenorphine with highly selective ligands for mu, delta and kappa, subsites. Following threshold cerebral ischemia (rCBF < 10 ml/100 g/min) there was a 2 to 3 fold increase in the 3 opioid receptor subtype concentrations at 10 min following the release of MCAO. Further, 56% of the cats depicted early postischemic hyperemia BBB opening, at 1 h and 3 h following the release of occlusion, with significant subsequent progression of brain edema. We believe that the enhanced brain opioid activity may be relevant to the neuronal damage caused by the early postischemic BBB opening.

Topics: Animals; Blood-Brain Barrier; Brain; Brain Edema; Cats; Diprenorphine; Ischemic Attack, Transient; Male; Nerve Degeneration; Opioid Peptides; Receptors, Opioid; Regional Blood Flow; Reperfusion Injury

We investigated alterations in opiate-binding sites in the upper dorsal horn after transection of the related peripheral sensory nerve in rats. The binding of (3H)diprenorphine was measured autoradiographically. The findings indicated a shift of the binding sites, rather than a degenerating disappearance, with a decrease in nerve fibers but an increase in nerve cells. This may be due to latent opiate-binding sites becoming manifest.

Topics: Animals; Autoradiography; Denervation; Diprenorphine; Ganglia, Spinal; Morphinans; Nerve Degeneration; Nociceptors; Rats; Receptors, Opioid; Spinal Nerve Roots

The substance P content, glutamic acid decarboxylase and choline acetyltransferase activities and the level of [3H]diprenorphine binding were measured in various regions of the lumbar spinal cord of rats after unilateral section of the sciatic nerve or after dorsal rhizotomy. Sciatic nerve section produced a 75--80% depletion of substance P in the dorsal horn but did not change the substance P content of the ventral horn. The onset of substance P depletion occurred within 7 days and was maintained for 2 months. The substance P content of the dorsal root ganglia and both the peripheral and central branches of primary sensory neurons was also reduced after sciatic nerve section. Glutamic acid decarboxylase and choline acetyltransferase activity were unchanged; however, a small decrease in opiate receptor binding occurred 1 month after nerve section. Dorsal rhizotomy produced an 80% depletion of substance P in the dorsal horn. In addition, the substance P content of the ventral horn was significantly reduced. Glutamic acid decarboxylase activity in the dorsal horn was unaffected by dorsal rhizotomy whereas opiate receptor binding was reduced by 40%. From these studies it appears that peripheral nerve injury results in the degeneration of primary sensory neurons which contain and release substance P as neurotransmitter.

Topics: Afferent Pathways; Animals; Choline O-Acetyltransferase; Diprenorphine; Functional Laterality; Ganglia, Spinal; Glutamate Decarboxylase; Male; Nerve Degeneration; Neurons; Rats; Receptors, Opioid; Sciatic Nerve; Spinal Cord; Spinal Nerve Roots; Substance P