Peripheral mechanisms of pain and analgesia

Christoph Stein, J. David Clark, Uhtaek Oh, Michael R. Vasko, George L. Wilcox, Aaron C. Overland, Todd W. Vanderah, Robert H. Spencer

Research output: Contribution to journalReview articlepeer-review

180 Scopus citations

Abstract

This review summarizes recent findings on peripheral mechanisms underlying the generation and inhibition of pain. The focus is on events occurring in peripheral injured tissues that lead to the sensitization and excitation of primary afferent neurons, and on the modulation of such mechanisms. Primary afferent neurons are of particular interest from a therapeutic perspective because they are the initial generator of noxious impulses traveling towards relay stations in the spinal cord and the brain. Thus, if one finds ways to inhibit the sensitization and/or excitation of peripheral sensory neurons, subsequent central events such as wind-up, sensitization and plasticity may be prevented. Most importantly, if agents are found that selectively modulate primary afferent function and do not cross the blood-brain-barrier, centrally mediated untoward side effects of conventional analgesics (e.g. opioids, anticonvulsants) may be avoided. This article begins with the peripheral actions of opioids, turns to a discussion of the effects of adrenergic co-adjuvants, and then moves on to a discussion of pro-inflammatory mechanisms focusing on TRP channels and nerve growth factor, their signaling pathways and arising therapeutic perspectives.

Original languageEnglish (US)
Pages (from-to)90-113
Number of pages24
JournalBrain Research Reviews
Volume60
Issue number1
DOIs
StatePublished - Apr 2009

Bibliographical note

Funding Information:
Supported by grants from the Deutsche Forschungsgemeinschaft (KFO 100, STE 477/9-1, GRK 1258), Bundesministerium für Bildung und Forschung (MedSys 0101-31P5783) and the International Anesthesia Research Society to C.S., from NIH/NIDA (DA021332) to J.D.C., from NIH (NS048565) to M.R.V., from NIH (R01 DA 15438) to G.L.W., and from an NIH training grant (T32 DA07234-20) in support of A.C.O.

Keywords

  • Adrenergic receptor
  • Inflammation and cytokine
  • Nerve growth factor (NGF)
  • Opioid receptor
  • Peripheral analgesia
  • Primary afferent
  • Pruritus
  • TRPV1

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