“Tumor necrosis factor-α (TNF-α) is an established pain modulator in the peripheral nervous system. Elevated levels of TNF-α in dorsal root ganglion (DRG) neurons reportedly is critical for neuropathic pain processing. It has been shown that the production of nitric oxide, a key player in the development and maintenance of nociception, depends on the expression of nitric oxide synthases (NOSs) and their activities.

Accumulating evidence also supports an important role of cannabinoids in modulating neuropathic pain.

In this study, we explored the effects and the underlying mechanisms of crosstalk between TNF-α and cannabinoid on the expression/activity of NOS in DRG neurons.

Our findings suggest that TNF-α induces the expression/activity of nNOS in DRG neurons by increasing its mRNA stability by a p38 MAPK-dependent mechanism; WIN-55 inhibits this effect of TNF-α by inhibiting p38 MAPK via CB2.

By linking the functions of TNF-α, NOS and cannabinoid in DRG neurons, this study adds new insights into the molecular mechanisms underlying the pharmacologic effects of cannabinoids on neuropathic pain as well as into the pathophysiology of neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/29786105

https://www.spandidos-publications.com/10.3892/ijmm.2018.3687