Acamprosate effect on neuropathic pain in rats: With emphasis on the role of ERK/MAPK pathway and SCN9A sodium channel.

BACKGROUND

Neuropathic pain is a chronic pain owing to nerve damage or diseases of the central nervous system (CNS). The expression of SCN9A, which encodes the Nav1.7 voltage-gated sodium channel and ERK have been found to change significantly in many cases of neuropathic pain. Here, we investigated effects of acamprosate on neuropathic pain, taking into account the crucial roles of SCN9A, the ERK signaling pathway, and inflammatory markers in a rat model of chronic constriction injury (CCI).

METHODS

Acamprosate (300 mg/kg) was injected intraperitoneally (i.p.) for 14 days. The tail-immersion, acetone, and formalin tests were used to determine behavioral tests such as heat allodynia, cold allodynia, and chemical hyperalgesia, respectively. Lumbar spinal cord was extracted and processed for Nissl staining. The amount of spinal SCN9A expression and ERK phosphorylation were examined using ELISA assay.

RESULTS

The expression of SCN9A, ERK, inflammatory cytokines (IL-6 and TNF-α), allodynia and hyperalgesia significantly increased on days 7 and 14 following CCI. The treatment not only reduced neuropathic pain but also blocked CCI's effects on SCN9A upregulation and ERK phosphorylation.

CONCLUSION

This research demonstrated that acamprosate reduces the neuropathic pain induced by CCI of the sciatic nerve in rats by preventing cell loss, inhibiting spinal SCN9A expression, ERK phosphorylation, and inflammatory cytokines, suggesting potential therapeutic implications of acamprosate administration for the treatment of neuropathic pain.