Down-regulation of GFRα-1 expression by antisense oligodeoxynucleotide aggravates thermal hyperalgesia in a rat model of neuropathic pain

Glial cell line-derived neurotrophic factor (GDNF) has been hypothesized to play an important role in the modulation of nociceptive signals especially during neuropathic pain. The present study examined the expression of GDNF and GFRα-1 (the high-affinity receptor of GDNF) in dorsal root ganglions (DRG) in a rat model of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic nerve. In order to address the role of GDNF and GFRα-1 in neuropathic pain, antisense oligodeoxynucleotide (ODN) specifically against GFRα-1 was intrathecally administered to result in down-regulation of GFRα-1 expression. The results showed that both the protein and mRNA levels of GDNF and GFRα-1 were significantly increased after CCI, while the thermal hyperalgesia of neuropathic pain rats could be significantly aggravated by antisense ODN treatment, but not by normal saline (NS) or mismatch ODN treatment. The present study demonstrated that endogenous GDNF and GFRα-1 might play an anti-hyperalgesic role in neuropathic pain of rats. In addition, we found a down-regulation of somatostatin (SOM) in DRG and spinal dorsal horn after expression of GFRα-1 was knocked down, which suggested the possible relationship between the anti-hyperalgesic effect of GDNF and GFRα-1 on neuropathic pain and endogenous SOM.