Botulinum toxin type A alleviates chronic post-thoracotomy pain by inhibiting the HMGB1-mediated TLR4/NF-KB signaling pathway in rats

The purpose of this study was to establish a chronic pain model after thoracotomy in rats and investigate the effects of BTX-A on spinal inflammation and the chronic hyperalgesia of rats. SD rats were used to established animal model of chronic post-thoracotomy pain (CPTP) by Buvanendran method, and a control group and sham group were established. On the third day postoperatively, the rats were given subcutaneous injection of BTX-A. Pain behavior tests of rats, including Mechanical withdrawal threshold (MWT) and cold hyperalgesia threshold, were performed before operation and postoperatively. Finally, the rats were killed to collect spinal cord tissue samples for pathological examination or protein expression detection. After the operation, all model rats showed a decrease in MWT values and an increase in the number of positive reactions to cold acetone stimulation, the model was successfully established. In contrast to the model group, the MWT in the M + BTX-A group was significantly higher, and the number of positive reactions of cold acetone stimulation was also significantly decreased. HE staining results showed that the nucleus of spinal cord tissue was abnormally enlarged and inflammatory cells were increased in the model group. The cell morphology of M + BTX-A group was close to normal. In addition, BTX-A significantly decreased the levels of OX-42, HMGB1, TLR4, IL-10, TNF-α, p-P65 and p-IKB-α in tissues. BTX-A was able to effectively relieve chronic post-thoracotomy pain and decrease spinal inflammation in CPTP model rats by suppressing microglial activation in spinal cord by inhibiting HMGB1-mediated TLR4/NF-κB signaling pathway. Botulinum toxin type A inhibits microglial activation in thoracotomy rats.