Purpose
Osteoarthritis (OA) is the most common cause to lead to chronic pain. Transcranial direct current stimulation (tDCS) has been widely used to treat nerve disorders and chronic pain. The benefits of tDCS for chronic pain are apparent, but its analgesic mechanism is still unclear. This study observed the analgesic effects of tDCS on OA-induced chronic pain and the changes of NMDA receptor levels in PAG after tDCS treatment in rats to explore the analgesic mechanism of tDCS.
Methods
After establishing chronic pain by injecting monosodium iodoacetate (MIA) into the rat ankle joint, the rats received tDCS for 14 consecutive days (20 min/day). Before tDCS treatment, Ifenprodil (the selective antagonist of NMDAR2B) was given to rats in different ways: intracerebroventricular (i.c.v.) injection or intraperitoneal (i.p.) injection. The Von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. The expression level of NMDAR2B was evaluated in midbrain periaqueductal gray (PAG) by Western blot. In addition, NMDAR2B and c-Fos were observed by the Immunohistochemistry staining after tDCS treatment.
Results
The mechanical allodynia and thermal hyperalgesia were produced after MIA injection. However, tDCS treatment reverted the mechanical allodynia and thermal hyperalgesia. Moreover, tDCS treatment significantly increased the expression of NMDAR2B and the proportion of positive stained cells of NMDAR2B. Besides that, the tDCS treatment also decreased the proportion of positive stained cells of c-Fos in PAG. However, these changes did not occur in the rats given the Ifenprodil (i.c.v.).
Conclusion
These results indicate that tDCS may increase the expression of NMDA receptors in PAG and strengthen the NMDA receptors-mediated antinociception to alleviate OA-induced chronic pain in rats.
Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.
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