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

Abstract

Partial sciatic nerve injury causes neuropathic pain associated with behavioral changes such as spontaneous pain, hyperalgesia and allodynia. Both central and peripheral sensitization of pain pathways are likely to be involved in these alterations. Nerve injury induced plastic changes in the dorsal horn, where the second relay nociceptive neurons are located, may contribute to the central sensitization process. It is thus important to establish the intracellular events through which a partial nerve injury can induce plasticity leading to neuropathic pain. In this study, we investigated whether partial sciatic nerve ligation (PSNL), a well-characterized neuropathic pain model, is able to induce the phosphorylation of a transcription factor, known as the cyclic AMP response element-binding protein (CREB) which is believed to be involved in the transcriptional regulation of many genes. Using 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. Interestingly, the majority of pCREB-IR cells expressed protein kinase Cγ, an enzyme shown to be involved in the development of neuropathic pain in PSNL model. Taken together, these results suggest that increased CREB phosphorylation induced by PSNL may be one of the key molecular events leading to synaptic alterations and persistent pain in the PSNL model of neuropathic pain.