The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain.

Effective treatments for patients suffering from chronic pain remain an area of intense focus within the pharmaceutical industry, as the development of novel therapies would help to treat an area of significant unmet medical need. The successful development of pharmacological agents to treat inflammatory and neuropathic pain conditions relies on a thorough understanding of the mechanisms that underlie the development and maintenance of chronic pain states. The goal of this review is to highlight recent discoveries regarding the intracellular signaling mechanisms that appear to play a critical role in persistent inflammatory and neuropathic pain. The review will focus on the mitogen activated protein kinase family of enzymes and the data suggesting that treatments designed to inhibit the activation of these enzymes may lead to significant advancements in the treatment of chronic pain. The review will also highlight the important interplay between neurons and non-neuronal cells (i.e., microglia and astrocytes) within the dorsal horn of the spinal cord in the generation and maintenance of chronic inflammatory and neuropathic pain.