SPINAL OPIOID MU-RECEPTOR EXPRESSION IN LUMBAR SPINAL-CORD OF RATS FOLLOWING NERVE INJURY

Previous studies in rats have shown that spinal morphine loses potency and efficacy to suppress an acute nociceptive stimulus applied to the tail or the paw following injury to peripheral nerves by tight ligati on of the L5/L6 spinal nerves. Additionally, intrathecal (i.th.) morph ine is ineffective in suppressing tactile allodynia at fully antinocic eptive doses in these animals. The molecular basis for this loss of mo rphine potency and efficacy in nerve injury states is not known. One p ossible explanation for this phenomenon is a generalized, multi-segmen tal loss of opioid mu (mu) receptors in the dorsal horn of the spinal cord after nerve injury. This hypothesis was tested here by determinin g whether nerve injury produces (a) a decrease in mu receptors in the lumbar spinal cord; (b) a decrease in the affinity of ligand-receptor interaction, (c) a decrease in the fraction of high-affinity state of the mu receptors and (d) a reduced ability of morphine to activate G-p roteins via mu receptors. Lumbar spinal cord tissues were examined 7 d ays after the nerve injury, a time when stable allodynia was observed. At this point, no differences were observed in the receptor density o r affinity of [H-3]DAMGO (mu selective agonist) or [H-3]CTAP (mu selec tive antagonist) in the dorsal quadrant of lumbar spinal cord ipsilate ral to nerve injury. Additionally, no change in morphine's potency and efficacy in activating G-proteins was observed. In contrast, staining for mu opioid receptors using mu-selective antibodies revealed a disc rete loss of mu opioid receptors localized ipsilateral to the nerve in jury and specific for sections taken at the L6 level. At these spinal segments, mu opioid receptors were decreased in laminae I and II. The data indicate that the loss of mu opioid receptors are highly localize d and may contribute to the loss of morphine activity involving input at these spinal segments (e.g., foot-flick response). On the other han d, the lack of a generalized loss of opioid mu receptors across spinal segments makes it unlikely that this is the primary cause for the los s of potency and efficacy of mu opioids to suppress multi-segmental re flexes, such as the tail-flick response. (C) 1998 Elsevier Science B.V . All rights reserved.