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

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.