PT  - JOURNAL ARTICLE
AU  - Luiz F. Ferrari
AU  - Oliver Bogen
AU  - Jon D. Levine
TI  - Role of Nociceptor αCaMKII in Transition from Acute to Chronic Pain (Hyperalgesic Priming) in Male and Female Rats
AID  - 10.1523/JNEUROSCI.1785-13.2013
DP  - 2013 Jul 03
TA  - The Journal of Neuroscience
PG  - 11002--11011
VI  - 33
IP  - 27
4099  - http://www.jneurosci.org/content/33/27/11002.short
4100  - http://www.jneurosci.org/content/33/27/11002.full
SO  - J. Neurosci.2013 Jul 03; 33
AB  - We have previously shown that activation of protein kinase Cε (PKCε) 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 PKCε, and consequent translation of mRNAs in the peripheral terminal of the nociceptor. Since α calmodulin-dependent protein kinase II (αCaMKII), 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 PKCε can be prevented by inhibition of αCaMKII. In addition, direct activation of αCaMKII induces priming, which was not prevented by pretreatment with PKCε antisense, suggesting that αCaMKII is downstream of PKCε in the induction of priming. Activation of ryanodine receptors (RyRs), which can lead to activation of αCaMKII, also induced priming, in a calcium- and αCaMKII-dependent manner. Similarly, inhibition of the RyR and a calcium buffer prevented induction of priming by PKCε. Unlike activation of PKCε, ryanodine and αCaMKII induced priming in female as well as male rats. Our results demonstrate a contribution of αCaMKII to induction of hyperalgesic priming, a phenomenon implicated in the transition from acute to chronic pain.