Thalidomide represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling

- Thalidomide inhibited the expression of pro-inflammatory mediators in vitro.
- Thalidomide inhibited the expression of matrix metalloproteinases in vitro.
- Thalidomide inhibited the expression of radiculopathic pain in vivo.
- Thalidomide could treat pain and inflammation in degenerative disc disease.

Intervertebral disc (IVD) disease, the most common cause of disc failure and low back pain, is characterized by age-related changes in the adult disc. In this study we aimed to analyze the potential of thalidomide for the treatment of IVD disease, through identifying and explaining its anti-inflammatory and anti-catabolic activity in both in vitro IVD cell culture and in vivo animal model. Inflammatory response was induced by IL-1β, then the activity and expression of inflammatory mediators and pathways were assessed in the presence or absence of thalidomide. The p38 inhibitor SB203580 was also used to investigate the involvement of the MAPK pathway in the observed effects. Moreover the analgesic properties of thalidomide were analyzed by the von Frey filament test in Sprague-Dawley rats. Our results indicated that thalidomide significantly inhibited the expression of pro-inflammatory mediators and matrix metalloproteinases in vitro, as well as radiculopathic pain in vivo, most probably by modulation of the activity of IRAK-1 and its downstream effectors p38, JNK and NF-κB. Our current study strongly supports the potential of thalidomide for the treatment of pain and inflammation in degenerative disc disease.

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