PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia.
Furthermore, intrathecal injection of PKC but not PKA blocker prevented the development of chronic pain and PKC agonist was sufficient to induce prolonged hyperalgesia response after acid injection.
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.