Increased phosphorylation of cyclic AMP response element-binding protein (CREB) in the superficial dorsal horn neurons following partial sciatic nerve ligation

Partial sciatic nerve injury causes neuropathic pain associated with behavi oral changes such as spontaneous pain, hyperalgesia and allodynia. Both cen tral and peripheral sensitization of pain pathways are likely to be involve d in these alterations. Nerve injury induced plastic changes in the dorsal horn, where the second relay nociceptive neurons are located, may contribut e to the central sensitization process. It is thus important to establish t he intracellular events through which a partial nerve injury can induce pla sticity leading to neuropathic pain. In this study, we investigated whether partial sciatic nerve ligation (PSNL), a well-characterized neuropathic pa in model, is able to induce the phosphorylation of a transcription factor, known as the cyclic AMP response element-binding protein (CREB) which is be lieved to be involved in the transcriptional regulation of many genes. Usin g immunocytochemistry, we found that 3 weeks following PSNL, the number of phosphorylated (p) CREB-IR cells was significantly increased in the injured side dorsal horn of rats, particularly in the superficial laminae. Interes tingly, the majority of pCREB-IR cells expressed protein kinase C gamma, an enzyme shown to be involved in the development of neuropathic pain in PSNL model. Taken together, these results suggest that increased CREB phosphory lation induced by PSNL may be one of the key molecular events leading to sy naptic alterations and persistent pain in the PSNL model of neuropathic pai n. (C) 2001 International Association for the Study of Pain. Published by E lsevier Science B.V. All rights reserved.