Bilateral and differential changes in spinal mu, delta and kappa opioid binding in rats with a painful, unilateral...

Quantitative receptor autoradiography was used to assess mu, delta and kappa opioid binding sites in the lumbar spinal cord of rats with neuropathic pain due to a unilateral chronic constriction injury (CCI) of the sciatic nerve. Sections from spinal segment L4 were obtained from animals of treatment groups (left side CCI, right side sham-operated) at 2, 5 and 10 days post surgery and from control animals (left side sham-operated, right side untreated) 10 days post surgery. Autoradiograms were made of the equilibrium binding of the highly selective opioid radioligands, 3H-sufentanil (mu ligand), 3H-[D-Pen2,5]-enkephalin (DPDPE, delta ligand) and 3H-U69593 (Upjohn compound, kappa ligand). Computerized grain counting was performed on discrete regions of the autoradiograms corresponding to areas within laminae I-II, V and X on both sides of the spinal cord; the sciatic nerve's small diameter axons terminate in these areas. With a single exception, there were no changes in binding for any of the ligands in any of the areas at 10 days post surgery in the control animals. The exception was a small increase in kappa binding in laminae I-II on the sham-operated side. After nerve injury, however, there were marked changes (compared to the sham-operated side of the control animals) in the amount of binding for all ligands, and most of these changes were bilateral. Mu binding was significantly increased 2-5 days post injury, bilateral to the injury in laminae V and X but only ipsilateral in laminae I-II. Mu binding in all laminae gradually declined towards control values. By day 10 significant differences remained only in lamina X. Delta binding displayed little change at 2 days post injury but declined gradually thereafter. By day 10 post injury, delta binding was significantly decreased in all three areas; these decreases were bilateral in all areas and approximately equal in laminae V and X but were significantly greater on the nerve-injured side in laminae I-II. Kappa binding displayed a complex pattern of changes at day 2 post injury: a significant increase in ipsilateral laminae I-II and a significant increase in contralateral lamina X but no change on either side in lamina V. There was a rapid decrease in kappa binding in all three areas on both sides of the spinal cord by day 5 post injury, and these decreases were little changed by day 10.(ABSTRACT TRUNCATED AT 400 WORDS)