Bilateral and differential changes in spinal mu, delta and kappa opioid binding in rats with a painful, unilateral neuropathy.
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)
Stevens
Craig W
CW
Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis, MN 55455 USA Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 USA.
Kajander
Keith C
KC
Bennett
Gary J
GJ
Seybold
Virginia S
VS
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology; D044482:Benzeneacetamides; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins; D005283:Fentanyl / Q000031:analogs & derivatives; D008024:Ligands; D008297:Male; D009422:Nervous System Diseases / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D011759:Pyrrolidines; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012684:Sensory Thresholds / Q000502:physiology; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism; D017409:Sufentanil
D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D008024:Ligands; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020881:Enkephalin, D-Penicillamine (2,5)-; D017409:Sufentanil; C045444:U 69593; D005283:Fentanyl