The role of the spinal cyclooxygenase (COX) for incisional pain in rats at different developmental stages

摘要

Abstract Background Cyclooxygenase enzymes (COX)‐1 and COX‐2 are important targets for pain relief after surgery, but the spinal contribution of both isoforms is still unclear, e.g., from a developmental point of view. Here, we studied changes of spinal COX‐1 and COX‐2 expression and their functional relevance in rats of different ages for pain‐related behaviour after incision. Methods Mechanical paw withdrawal thresholds (PWT) were assessed before and after incision and after intrathecal administration (IT) of SC‐560 (COX‐1 inhibitor) or NS‐398 (COX‐2 inhibitor) in rats aged 5, 14 and 28?days (P5, P14, P28). Furthermore, spinal expressions of COX m‐RNA and proteins were investigated. Results In P5 rats, only IT‐administered NS‐398 but not SC‐560 significantly reversed the decreased PWT after incision. In P14 rats, none of the substance modified PWT, and in P28 rats, only SC‐560 increased PWT. Spinal COX‐2 mRNA and protein were increased in P5 but not in P14 and P28 rats after incision. Whereas COX‐2 is located in spinal neurons, COX‐1 is mainly found in spinal microglia cells. Conclusion Our results demonstrate a possible developmental transition from COX‐2 to COX‐1 activation. Whereas in adult rats spinal COX‐1 but not COX‐2 is involved in pain‐related behaviour after incision, it seems opposite in P5 rats. Interestingly, in P14, neither COX‐1 nor COX‐2 seems to play a role. This switch may relate to altered neuronal/microglia activation. Our findings indicate specific mechanisms to pain after incision that are age‐dependent and may guide further research improving paediatric pain management. Significance Postoperative pain in pediatric patients after surgery is still poorly controlled; this might contribute to long‐lasting alteration in the nociceptive system and prolonged chronic pain. Here we show a possible developmental switch in the COX‐dependent pathway for nociceptive spinal transmission that may explain why pain management in young children needs to be related to age‐dependent mechanisms.