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 wid ely studied as mediators of pain transmission. The expression of neuro kinin-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 the se opiates similarly alter the expression of substance P-, neurokinin B-, neurokinin-1 receptor- and neurokinin-3 receptor-encoding messenge r RNAs in spinal systems following formalin-induced nociception. Expre ssion levels of various messenger RNAs were quantitated using solution hybridization-nuclease protection assays. Six hours after hindpaw tre atment, the levels of substance P-encoding preprotachykinin messenger RNA in the lumbar dorsal root ganglia and neurokinin B, neurokinin-1 r eceptor and neurokinin-3 receptor messenger RNAs in the lumbar dorsal horn were increased by approximately two-fold as compared to sham-trea ted controls. Pretreatment with naltrexone resulted in a further incre ase in the nociception-induced substance P messenger RNA expression in the dorsal root ganglia; preprotachykinin messenger RNA expression wa s not affected by morphine. Nociception-induced neurokinin-1 receptor messenger RNA expression in the dorsal horn was blocked by morphine, b ut was not affected by naltrexone. Both morphine and naltrexone blocke d the formalin-induced increases in neurokinin B and neurokinin-3 rece ptor messenger RNA levels. Increased neurokinin B messenger RNA expres sion may reflect increased neurokinin B turnover in spinal interneuron s activated by nociception. Neurokinin-3 receptor messenger RNA expres sion levels varied closely with, and thus may be regulated by, the lev els of neurokinin B messenger RNA in the same regions. The results of this study indicate that pretreatment with opiate ligands modulates th e expression of tachykinin peptide and neurokinin receptor encoding mR NAs in spinal systems following a peripheral chemogenic inflammatory s timulus. Thus, endogenous opioid systems may be involved in activity-i nduced changes in the expression of spinal tachykinin peptides and neu rokinin receptors.