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Intrathecal Infusion of Pyrrolidine Dithiocarbamate for the Prevention and Reversal of Neuropathic Pain in Rats Using a Sciatic Chronic Constriction Injury Model
  1. Yun-Dan Pan, PhD, MD,
  2. Qu-Lian Guo, PhD, MD,
  3. E. Wang, PhD, MD,
  4. Zhi Ye, PhD, MD,
  5. Zheng-Hua He, PhD, MD,
  6. Wang-Yuan Zou, PhD, MD,
  7. Zhi-Gang Cheng, PhD, MD and
  8. Yun-Jiao Wang, PhD, MD
  1. From the Department of Anesthesiology, Xiangya hospital of Central South University, Changsha, Hunan Province, People's Republic of China.
  1. Address correspondence to: Qu-Lian Guo, PhD, MD, Department of Anesthesiology, Xiangya hospital of Central South University, Changsha 410008, Hunan Province, People's Republic of China (e-mail: QULIANGUOPYD{at}163.com).

Abstract

Background and Objectives: Recent studies have suggested that nuclear factor κB (NF-κB) may play a role in mediating nerve injury-induced neuropathic pain. Here, we examined the effects of intrathecal pyrrolidine dithiocarbamate (PDTC), a NF-κB 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 1 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 1 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-κB pathway may contribute to spinal microglial activation and CX3CR1 up-regulation.

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Footnotes

  • This work was supported by grants from the National Nature Foundation (30772080 and 30801074).