THE FORMALIN-INDUCED EXPRESSION OF TACHYKININ PEPTIDE AND NEUROKININ RECEPTOR MESSENGER-RNAS IN RAT SENSORY GANGLIA AND SPINAL-CORD IS MODULATED BY OPIATE PREADMINISTRATION

Tachykinin peptides such as substance P and neurokinin B have been widely studied as mediators of pain transmission. The expression of neurokinin-1 and neurokinin-3 receptor messenger RNAs in the spinal cord is increased following intense nociception. The opiate ligands morphine and naltrexone alter behavioral responses to formalin-induced pain and alter evoked substance P release. This study investigated whether these opiates similarly alter the expression of substance P-, neurokinin B-, neurokinin-1 receptor- and neurokinin-3 receptor-encoding messenger RNAs in spinal systems following formalin-induced nociception. Expression levels of various messenger RNAs were quantitated using solution hybridization-nuclease protection assays. Six hours after hindpaw treatment, the levels of substance P-encoding preprotachykinin messenger RNA in the lumbar dorsal root ganglia and neurokinin B, neurokinin-1 receptor and neurokinin-3 receptor messenger RNAs in the lumbar dorsal horn were increased by approximately two-fold as compared to sham-treated controls. Pretreatment with naltrexone resulted in a further increase in the nociception-induced substance P messenger RNA expression in the dorsal root ganglia; preprotachykinin messenger RNA expression was not affected by morphine. Nociception-induced neurokinin-1 receptor messenger RNA expression in the dorsal horn was blocked by morphine, but was not affected by naltrexone. Both morphine and naltrexone blocked the formalin-induced increases in neurokinin B and neurokinin-3 receptor messenger RNA levels. Increased neurokinin B messenger RNA expression may reflect increased neurokinin B turnover in spinal interneurons activated by nociception. Neurokinin-3 receptor messenger RNA expression levels varied closely with, and thus may be regulated by, the levels of neurokinin B messenger RNA in the same regions. The results of this study indicate that pretreatment with opiate ligands modulates the expression of tachykinin peptide and neurokinin receptor encoding mRNAs in spinal systems following a peripheral chemogenic inflammatory stimulus. Thus, endogenous opioid systems may be involved in activity-induced changes in the expression of spinal tachykinin peptides and neurokinin receptors.