title: Role of nociceptor αCaMKII in transition from acute to chronic pain (hyperalgesic priming) in male and female rats.
abstract: 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.
authors.affiliation: Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Ferrari
authors.forename: Oliver
authors.initials: O
authors.lastname: Bogen
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D059787:Acute Pain / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D059350:Chronic Pain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006930:Hyperalgesia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517675:Camk2a protein, rat