Immediate-early genes expression in spinal cord as related to acute noxious stimulus

During the "central sensitization" phenomenon, noxious stimuli lead to expression of IEGs (c-fos, c-jun, krox-24); their proteic products have been postulated to convert short-term stimulations into long-lasting responses in dorsal-horn neurons. The aim of this study was to verify if analgesic drugs, such as morphine and ketorolac, may affect the c-fos protooncogene expression by using a method highly sensitive and specific, based on transformation of activated c-fos specific mRNA in cDNA (reverse transcription), its amplification (PCR) and final visualization by electrophoresis on agarose gel. Male Wistar rats were submitted to various stimuli in order to assess which procedure resulted in genic derepression; monolateral sciatic nerve ligature appeared to be the most effective. When the animals were pretreated with morphine or ketorolac and subsequently exposed to the monolateral sciatic nerve ligature, or treated with ketorolac immediately after the same painful stimulus, we found that only pretreatment with morphine completely blocked c-fos depression. Our results confirm that pretreatment with opioids is able to prevent IEGs derepression and the central sensitization phenomenon.