Spinal PKC activation - Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats.

Spinal PKC activation - Induced neuronal HMGB1 translocation contributes to hyperalgesia in a bone cancer pain model in rats. Exp Neurol. 2018 Feb 08;: Authors: An K, Rong H, Ni H, Zhu C, Xu L, Liu Q, Chen Y, Zheng Y, Huang B, Yao M Abstract Bone cancer pain (BCP) remains a serious complication of malignancy, which is an intractable clinical problem due to the gap in knowledge of its underlying mechanisms. Recent studies have demonstrated that the major involvement of neuroinflammation, particularly high-mobility group box 1 (HMGB1), which was identified as a late mediator of inflammation, in a number of pain conditions. However, the underlying mechanisms and functions of HMGB1 release in spinal cord, and its contributions to the development of BCP as well, are poorly understood. 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. Our results showed that PKC activation and HMGB1 release in spinal neurons as well as mechanical allodynia in BCP rats, were all attenuated by intrathecal administration of the PKC inhibitor Gö6983 and aggravated by its activator PMA. Intrathecal administration of anti-HMGB1 antibody also alleviated hypersensitivity caused by BCP. Meanwhile, phospho-PKC and cellular HMGB1 were found co-localized in neurons, but not in microglia and...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research