Opioidergic and adrenergic modulation of formalin-evoked spinal c-fos mRNA expression and nocifensive behavior in the rat

Abstract Fos protein expression has been used to reflect neuronal activation in pain processing pathways although analgesics may uncouple behavioral and Fos responses. We determine whether formalin-induced spinal c- fos mRNA expression (Northern blotting) correlates with nocifensive behavior following pretreatment with morphine, the α 2 -adrenoceptor agonist dexmedetomidine, or their respective antagonists naloxone and atipamezole. Both opiate and α 2 -adrenoceptor agonists reduced formalin-induced c- fos gene transcription and nocifensive behavior via their cognate receptors. Unexpectedly, blockade of either the opiate or α 2 -adrenergic receptors, alone, caused an increase in formalin-evoked c- fos mRNA; while blocking the opiate receptor had no effect on formalin-induced behavior, α 2 -adrenoceptor block had an analgesic effect, indicating discordance between c- fos message transcription and nocifensive behavior. We concluded that the formalin-induced spinal c- fos signal was a poor predictor of the behavioral response to pharmacological manipulation of pain processing pathways.