Anti-nociceptive and anti-inflammatory actions of sulforaphane in chronic constriction injury-induced neuropathic pain mice

Neuropathic pain is still considered as incurable disease as current therapies are not ideal in terms of efficacy and tolerability. It is imperative to search for novel drugs to obtain better treatments. Sulforaphane (SFN), a derivative of glucoraphanin present in cruciferous vegetables, exhibits therapeutic effects on inflammation-related diseases. Since inflammation plays an important role in regulating chronic pain, in the present study, we investigated anti-nociceptive effects of SFN and its underlying mechanisms in a neuropathic pain mouse model, sciatic nerve chronic constriction injury (CCI). SFN (0.1-100 mg/kg) was injected intraperitoneally for 7 days when pain behaviors, including mechanical allodynia and thermal hyperalgesia, reached to the maximum in CCI mice. We observed that SFN dose-dependently attenuated CCI-induced pain behavioral hypersensitivity, accompanied by reduction in pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6) and upregulation of an anti-inflammatory cytokine (IL-10). Moreover, SFN counteracted CCI enhancement of COX2 and iNOS in injured nerves, two key enzymes implicated in inflammation and neuropathic pain. Furthermore, pretreatment of naloxone, an antagonist of opioid receptors, significantly blocked SFN attenuation of behavioral hypersensitivity without affecting SFN modulation of inflammatory cytokines in CCI mice. Interestingly, CCI-induced increase in A mu-opioid receptors in injured sciatic nerves was further increased by SFN treatment. Taken together, SFN has both anti-nociceptive and anti-inflammatory actions.