Phosphorylation of c-Jun N-terminal kinase isoforms and their different roles in spinal cord dorsal horn and primary somatosensory cortex

The present study was undertaken to investigate whether isoforms of c-Jun N-terminal kinase (JNK 46 kDa and 54 kDa), one component of the mitogen-activated protein kinase (MAPK) family, might show region-related differential activation patterns in both naïve and pain-experiencing rats. In naïve rats, no significant difference was observed in total expression level of the two JNK isoforms between spinal cord and primary somatosensory cortex (S1 area). However, phosphorylated JNK 46 kDa was normally expressed in the S1 area, but not in the spinal cord, while neither of the two structures contained phosphorylated JNK 54 kDa. Subcutaneous bee venom (BV)-induced persistent pain stimulation resulted in a significant increase in the phosphorylation of both JNK isoforms in each area for a long period (lasting at least 48 h). Nevertheless, JNK 46 kDa exhibited a much higher activation than JNK 54 kDa in the spinal cord, whereas the same noxious stimulation elicited evident activation of JNK 54 kDa in the S1 area, leaving JNK 46 kDa less affected. Intraplantar injection of sterile saline solution, causing acute and transient pain, produced almost the same changes in activation profile of the two JNK isoforms as found in the BV-treated rats. These results implicate that individual members of the JNK family may be associated with specific regions of nociceptive processing. Also, the two JNK isoforms are supposed to function differently according to their locations within the rat central nervous system.