Botulinum Toxin Type A Reduces Pain and NF-κB Levels in a Rat Model of Complex Regional Pain Syndrome

Background: Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by severe and disproportionate symptoms, with incompletely understood mechanisms. Nuclear factor-kappa B (NF-κB), a key transcription factor in neuroinflammation and pain signaling, is upregulated in animal models of CRPS. Botulinum toxin type A (BTA) has analgesic efficacy in neuropathic pain; however, its effect on NF-κB in CRPS has not been evaluated. This study investigated whether BTA attenuates pain and suppresses NF-κB expression in a rat model of CRPS. Methods: A chronic post-ischemia pain (CPIP) model was induced in male Sprague-Dawley rats. After induction, rats were randomly assigned to receive either BTA or normal saline (NS) injection into the plantar surface of the ipsilateral hind paw. A separate sham group underwent anesthesia without CPIP induction or injection. Mechanical thresholds were assessed, and NF-κB expression in the foot and spinal cord was quantified using enzyme-linked immunosorbent assays. Results: Following BTA injection, mechanical thresholds improved significantly compared with the NS group on days 14 and 21 (P = 0.039 and 0.010). NF-κB expression was significantly reduced in the ipsilateral foot (P = 0.009) and spinal cord (P = 0.025) of the BTA group compared with the NS group, whereas contralateral tissues showed no significant differences. Conclusion: These findings suggest an association between reduced NF-κB levels and the analgesic effects of BTA, supporting its potential therapeutic role in CRPS. Keywords: botulinum toxins, type A, complex regional pain syndrome, chronic pain, NF-κB, transcription factors