In the present research, neuropathic pain induced Nrf2 and HO-1 expression in the microglial cells of the spinal cord; Nrf2 and HO-1 were necessary to alleviate the hyperalgesia of CCI-induced rats; NaHS mitigated the hyperalgesia and allodynia induced by the CCI operation; and NaHS mitigated the excessive release of the cytokines TNF-α, IL-1β, IL-6 and HMGB1 via the Nrf2/HO-1 pathway in the microglial cells of the spinal cord.
In the present study, we examined the theory that PKC activation lead to nuclear translocation and cytosolic HMGB1 secretion, which subsequently induces spinal neuro inflammatory responses (cytokine release) causing hyperalgesia.
Tissue protein levels were determined by immunoblotting.Repeated i.p. administration of the anti-HMGB1-neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, prevented the development of hyperalgesia and/or allodynia induced by paclitaxel or vincristine in rats.A single i.p. or intraplantar (i.pl.) administration of the antibody or rhsTM reversed the chemotherapy-induced neuropathy.A single i.pl. administration of a TLR4 antagonist or low molecular weight heparin, known to inhibit RAGE, attenuated the hyperalgesia caused by i.pl.