Critical role of nociceptor plasticity in chronic pain
- PMID: 19781793
- PMCID: PMC2787756
- DOI: 10.1016/j.tins.2009.07.007
Critical role of nociceptor plasticity in chronic pain
Abstract
The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain. We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines. This phenomenon, "hyperalgesic priming," depends on the epsilon isoform of protein kinase C (PKCepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability. We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury, and generalized pain conditions, such as fibromyalgia.
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References
-
- International Association for the Study of Pain Task Force on Taxonomy: Classification of Chronic Pain Descriptions of Chronic Pain Syndromes and Definitions of Pain Terms. 1994. p. 222. - PubMed
-
- Magni G. On the relationship between chronic pain and depression when there is no organic lesion. Pain. 1987;31:1–21. - PubMed
-
- Croft P, et al. The prevalence of chronic widespread pain in the general population. J Rheumatol. 1993;20:710–713. - PubMed
-
- Brekke M, et al. Severity of musculoskeletal pain: relations to socioeconomic inequality. Soc Sci Med. 2002;54:221–228. - PubMed
-
- Casey C. Young, et al. Transition from acute to chronic pain and disability: A model including cognitive, affective, and trauma factors. Pain. 2007 - PubMed
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