(151) - Modulation of chronic post-thoracotomy pain by NK-1 neurons in the rostral ventromedial medulla is not paralleled by changes spinal MAPKinase activation

Abstract

Chronic post-operative pain after thoracotomy (CPTP) occurs in about half of the cases. Earlier findings in rat models of persistent neuropathic and inflammatory pain suggest that activation of different spinal Mitogen Activated Protein Kinases (MAPK) is critical for the initial and some longer-lasting pain, but no one has examined the MAPK activation pattern during chronic post-surgical pain. Recently we showed that ablation of Neurokinin-1 receptor (NK-1R)- expressing neurons in the rat rostral ventromedial medulla (RVM), by micro-injection of the specific neurotoxin SSP-SAP, (Sar9, Met(O2)11-Substance P conjugated to the ribosomal toxin saporin, 3 weeks before thoracotomy and rib retraction (TRR) was able to completely prevent CPTP, assayed by tactile hypersensitivity. Blank SAP, which has no cytotoxic activity, caused no change in CPTP. However, the same ablation procedure conducted post-surgically was less than fully effective to reverse these signs of CPTP. In the current study we tested the hypothesis that these differences in pain between pre-operative SSP-SAP (prevention), pre-operative Blank-SAP (control) and post-operative SSP-SAP (reversal) were correlated with the degree of long-term spinal MAPK activation (phosphorylation). We did this by assessing activated MAPKs, pERK, p-p38 and pJNK in spinal cord by Western blot and immunocytochemistry. Both assays revealed no differences in activated spinal MAPK levels assayed 5 weeks after surgery among the three groups, regardless of the pain level, showing that persistent pain in this model is not due to a persistent activation of spinal MAPKs.