Cell Signaling and the Genesis of Neuropathic Pain

Ru-Rong Ji^1* and Gary Strichartz^1,2

¹Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
²Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Gloss: Nerve injury not only leads to immediate sensations of pain, which serves an adaptive function, but can also lead to chronic pain, which is pathological. Although the mechanisms underlying the genesis and maintenance of neuropathic pain—the chronic pain that often, although in humans not always, results from nerve injury—remain incompletely understood, they are known to involve signaling pathways initiated both by inflammatory substances released from the damaged tissues and by aberrant firing of the damaged neurons. These signaling pathways lead to posttranslational modifications of existing proteins that appear to be involved in the genesis of neuropathic pain, as well as to changes in transcriptional activity that appear to be involved in its maintenance. This STKE Review explores the peripheral and central mechanisms underlying the initiation and maintenance of neuropathic pain and discusses the interactions between neurons and glia that are likely to prolong and enhance the pain that results from nerve injury. A deeper understanding of the mechanisms that contribute to neuropathic pain may be expected to lead to more effective methods of treating this chronic and disabling condition.

*Corresponding author. E-mail: rrji{at}zeus.bwh.harvard.edu

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