SUBARACHNOID MORPHINE REDUCES STIMULATION-INDUCED BUT NOT BASAL EXPRESSION OF PREPROENKEPHALIN IN RAT SPINAL-CORD

Background: To evaluate directly the possibility that the potent exoge nous opioid analgesic morphine may alter neuronal expression of opioid peptide genes, we assessed the effect of subarachnoid morphine on bas al and noxious stimulation-induced expression of preproenkephalin in s pinal cord neurons. Methods: Twenty male Sprague-Dawley rats were prep ared 48 h in advance with lumbar subarachnoid catheters. In the first phase, basal expression was evaluated in rats that received morphine 1 0 mu g or saline intrathecally (n = 5 per group). Subsequently, the ex periment was repeated (n = 5 per group), except that 10 min after morp hine or saline administration rats received a hindpaw footpad injectio n of 50 mu l 5% formalin. Rats were killed during pentobarbital anesth esia 2 h later, and messenger RNA transcribed from preproenkephalin wa s measured in lumbar spinal cord with quantitative in situ hybridizati on with a complementary sulfur 35-labeled oligonucleotide probe and em ulsion autoradiography. Results: In control (nonstimulated) rats, 20% of the neurons in laminae I-II and 10% of those in laminae III-IV expr essed preproenkephalin. Injection of formalin increased the fraction o f positive neurons by 34% (P < 0.05) and 20% (P < 0.05) in laminae I-I I and V-VI, respectively, but had no effect on expression in laminae I II-IV. Subarachnoid morphine did not alter basal expression of preproe nkephalin but markedly attenuated the noxious stimulation-induced incr ease in laminae I-II (P < 0.01) and V-VI (P < 0.05) by preventing the stimulation-evoked recruitment of preproenkephalin-expressing neurons that otherwise would have occurred. Conclusions: Subarachnoid morphine does not acutely alter basal expression of preproenkephalin in spinal cord neurons but inhibits the increase in preproenkephalin expression that would otherwise occur after noxious stimulation.