Intrathecal Infusion of Pyrrolidine Dithiocarbamate for the Prevention and Reversal of Neuropathic Pain in Rats Using a Sciatic Chronic Constriction Injury Model

Background and Objectives: Recent studies have suggested that nuclear factor kappa B (NE-kappa B) may play a role in mediating nerve injury-induced neuropathic pain. Here, we examined the effects of intrathecal pyrrolidine dithiocarbamate (PDTC), a NE-kappa B inhibitor, on the development of neuropathic pain, spinal microglial activation, and CX3CR1 expression induced by sciatic chronic constriction injury (CCI) model in rats. Methods: Under chloral hydrate anesthesia, male Sprague-Dawley rats (300-350 g) fitted with intrathecal catheters underwent either sciatic CCI or sham surgery. Intrathecal saline or PDTC (100 or 1000 pmol/d) was infused I day before or 3 days after CCI (n 8). The rat hind-paw withdrawal threshold to mechanical stimuli and withdrawal latency to radiant heat were determined before surgery and from days I to 7 after CCI. Spinal microglial activation was evaluated with OX-42 immunoreactivity, and spinal CX3CR1 expression was assessed by Western blotting. Results: Chronic constriction injury induced mechanical allodynia and thermal hyperalgesia and microglial activation as demonstrated by OX-42 expression. Whereas it had no apparent effect on spinal cord histology, intrathecal administration of PDTC prevented the development of the mechanical and thermal hyperalgesia and inhibited nerve injury induced microglial activation and spinal CX3CR1 expression. Conclusions: In this study, we have shown the protective effect of intrathecal PDTC on the development of nociceptive behaviors induced by CCI in rats. The activation of NF-kappa B pathway may contribute to spinal microglial activation and CX3CR1 up-regulation. (Reg Anesth Pain Med 2010;35: 231-237)