• Andre Laferrière, Mark H Pitcher, Anne Haldane, Yue Huang, Virginia Cornea, Naresh Kumar, Todd C Sacktor, Fernando Cervero, and Terence J Coderre.
• Department of Anesthesia, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, H3G 1Y6, Canada.
• Mol Pain. 2011 Jan 1; 7: 99.

BackgroundChronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC), PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH) mediating persistent pain.ResultsCutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH. Inhibiting spinal PKMζ, but not full-length PKCs, reversed plasticity-dependent persistent painful responses to hind paw formalin and secondary mechanical hypersensitivity and SCDH neuron sensitization after hind paw capsaicin, without affecting peripheral sensitization-dependent primary heat hypersensitivity after hind paw capsaicin. Inhibiting spinal PKMζ, but not full-length PKCs, also reversed mechanical hypersensitivity in the rat hind paw induced by spinal stimulation with intrathecal dihydroxyphenylglycine. Spinal PKMζ inhibition also alleviated allodynia 3 weeks after ischemic injury in rats with chronic post-ischemia pain (CPIP), at a point when allodynia depends on spinal changes. In contrast, spinal PKMζ inhibition did not affect allodynia in rats with chronic contriction injury (CCI) of the sciatic nerve, or CPIP rats early after ischemic injury, when allodynia depends on ongoing peripheral inputs.ConclusionsThese results suggest spinal PKMζ is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity.

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