Pain is initiated by activation of specific pain-sensitive neurons, or nociceptors, whose sensory terminals express a range of specific membrane receptors responsible for detecting different noxious stimuli. Activation of protein kinase C (PKC) by inflammatorymediators causes an increase in the sensitivity of the nociceptor to a variety of noxious stimuli. The best-studied target of PKC is the heat-sensitive ion channel, VR1, which is phosphoryatedby PKC-ε at two intracellular serine residues, leading to an increase in sensitivity to heat and other pain-causing stimuli such as acid. PKC is also involved at the stage of transmission ofnociceptive information to second-order neurons in the spinal cord. PKC-γ in postsynaptic neurons is specifically activated in neuropathic pain, leading to enhanced transmission, probablybecause of phosphorylation of NMDA receptors in the membrane of the postsynaptic neuron. PKC is also involved in the development of opiate tolerance, though the isotypes involved and the targets of its action are less well defined. Isotype-specific antagonists may have therapeutic potential as analgesics, as PKC-ε antagonists are likely to be active in reducing inflammatory pain, while PKC-γ antagonists may reduce neuropathic pain.
Involvement of PKC in the sensation of pain / Vellani, Vittorio; P. A., Mcnaughton. - STAMPA. - Second Edition:(2004), pp. 134-142.