Intrathecal injection of ozone alleviates CCI-induced neuropathic pain via the GluR6-NF-κB/p65 signalling pathway in rats

Ozone is widely used to relieve chronic pain clinically, but the precise mechanisms governing its action have yet to be elucidated. The present study aimed to investigate the mechanisms underlying the pain-alleviating effect of ozone in the chronic constriction injury (CCI) model of sciatic nerve in rats. Pain behaviours of rats were assessed by mechanical allodynia and thermal hyperalgesia. The expression of spinal glutamate receptor 6 (GluR6) and NF-kappa B/p65 was detected by western blotting and reverse transcription-quantitative PCR. Meanwhile, the expression of spinal IL-1 beta, IL-6 and TNF-alpha was detected by ELISA. GluR6 short interfering (si)RNAs were used intrathecally immediately following CCI once per day. Ozone (10, 20 or 30 mu g/ml) or oxygen was injected intrathecally on day 7 after CCI. The expression level of spinal GluR6 increased on day 3 and reached a peak on day 7 after CCI. The expression level of spinal IL-1 beta, IL-6, TNF-alpha and NF-kappa B/p65 also increased on day 7 after CCI. In addition, pre-intrathecal injection of GluR6 siRNAs inhibited pain behaviours and suppressed the expression of spinal GluR6, IL-1 beta, IL-6, TNF-alpha and NF-kappa B/p65 in CCI rats on day 7. Intrathecal injection of ozone was also observed to inhibit pain behaviours and suppress the expression of spinal GluR6, IL-1 beta, IL-6, TNF-alpha and NF-kappa B/p65 in CCI rats on day 7. The present study suggested that GluR6 served a pivotal role in neuropathic pain and that intrathecal injection of ozone may alleviate neuropathic pain via the GluR6-NF-kappa B/p65 signalling pathway.

Automated summary

The study revealed that ozone may alleviate neuropathic pain in rats with chronic constriction injury of the sciatic nerve by modulating the spinal GluR6-NF-kappa B/p65 signaling pathway. Additionally, ozone was found to inhibit pain behaviors and suppress the expression of spinal inflammatory mediators, indicating its potential as a therapeutic intervention for neuropathic pain.