RT Journal Article
SR Electronic
T1 Generation of a Pain Memory in the Primary Afferent Nociceptor Triggered by PKCε Activation of CPEB
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2018
OP 2026
DO 10.1523/JNEUROSCI.5138-11.2012
VO 32
IS 6
A1 Oliver Bogen
A1 Nicole Alessandri-Haber
A1 Carissa Chu
A1 Robert W. Gear
A1 Jon D. Levine
YR 2012
UL http://www.jneurosci.org/content/32/6/2018.abstract
AB Isolectin B4-positive [IB4(+)] primary afferent nociceptors challenged with an inflammatory or neuropathic insult develop a PKCε-dependent long-lasting hyperalgesic response to a subsequent challenge by the proinflammatory cytokine prostaglandin E2 (PGE2), a phenomenon known as hyperalgesic priming. Here we demonstrate that the neuroplasticity underlying nociceptor priming requires 72 h to be established; rats that have been challenged with the inflammatory mediator TNFα 24 or 48 h ahead of PGE2 do not show the enhanced and prolonged hyperalgesic response by which primed IB4(+)-nociceptors are being characterized. Moreover, as the underlying plasticity can be interrupted by the peripheral administration of the protein translation inhibitor anisomycin it is reflected by changes in the peripheral protein expression pattern. Finally, the induction of priming by the selective PKCε agonist, psi ε receptor for activated c kinase (ψεRACK) can be prevented, but not reversed by intrathecal injections of antisense oligodeoxynucleotides for the cytoplasmic polyadenylation element binding protein (CPEB) mRNA, a master regulator of protein translation that coimmunoprecipitated with PKCε and is almost exclusively expressed by IB4(+)-nociceptors. Our results suggest that CPEB is downstream of PKCε in the cellular signaling cascade responsible for the induction of priming, raising the intriguing possiblity that prion-like misfolding could be a responsible mechanism for the chronification of pain.