Role of Nociceptor  CaMKII in Transition from Acute to Chronic Pain (Hyperalgesic Priming) in Male and Female Rats (original) (raw)

2013, Journal of Neuroscience

We have previously shown that activation of protein kinase C (PKC) in male rats induces a chronic, long-lasting change in nociceptors such that a subsequent exposure to proinflammatory mediators produces markedly prolonged mechanical hyperalgesia. This neuroplastic change, hyperalgesic priming, is dependent on activation of cytoplasmic polyadenylation element-binding protein (CPEB), downstream of PKC, and consequent translation of mRNAs in the peripheral terminal of the nociceptor. Since ␣ calmodulin-dependent protein kinase II (␣CaMKII), a molecule implicated in neuroplasticity, is a target of CPEB and can also affect CPEB function, we investigated its role in the transition from acute to chronic pain. Priming induced by direct activation of PKC can be prevented by inhibition of ␣CaMKII. In addition, direct activation of ␣CaMKII induces priming, which was not prevented by pretreatment with PKC antisense, suggesting that ␣CaMKII is downstream of PKC in the induction of priming. Activation of ryanodine receptors (RyRs), which can lead to activation of ␣CaMKII, also induced priming, in a calcium-and ␣CaMKII-dependent manner. Similarly, inhibition of the RyR and a calcium buffer prevented induction of priming by PKC. Unlike activation of PKC, ryanodine and ␣CaMKII induced priming in female as well as male rats. Our results demonstrate a contribution of ␣CaMKII to induction of hyperalgesic priming, a phenomenon implicated in the transition from acute to chronic pain.