Protein kinase subtypes involved in injury-induced nociception.

Publisher Summary This chapter discusses the intracellular second messenger-activated protein kinase (PKA). It is important for the development of increased neuronal excitability and persistent nociceptive processing. Pharmacological studies using inhibitors or mice with a selective gene deletion suggest that PKA may mainly be involved in tissue injury and inflammation-evoked pain states, but not neuropathic pain, whereas protein kinase C (PKC) may be involved in all three of these persistent pain states. It appears that targeting PKA and/or PKC may be of potential medical benefit for the treatment of pain. However, most drug candidates that inhibit PKC that has been tested so far display little isoenzyme selectivity and are highly toxic. Targeting specific isoforms that are specifically involved in pain processing may be a more promising approach. It is also possible that targeting the proteins that function as anchoring proteins for activated PKC may provide efficacy with less toxicity. Further characterization of specific subtypes of protein kinases and their contribution to nociceptive processing is required for identification of new potential targets directed to signaling pathways for the treatment of persistent pain.