Peripheral mechanisms of pain and analgesia

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

Research output: Contribution to journalArticle

162 Citations (Scopus)

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

Fingerprint

Afferent Neurons
Analgesia
Opioid Analgesics
Pain
Nerve Growth Factor
Sensory Receptor Cells
Blood-Brain Barrier
Adrenergic Agents
Anticonvulsants
Spinal Cord
Brain
Therapeutics
Inhibition (Psychology)

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Stein, C., Clark, J. D., Oh, U., Vasko, M., Wilcox, G. L., Overland, A. C., ... Spencer, R. H. (2009). Peripheral mechanisms of pain and analgesia. Brain Research Reviews, 60(1), 90-113. https://doi.org/10.1016/j.brainresrev.2008.12.017

Peripheral mechanisms of pain and analgesia. / Stein, Christoph; Clark, J. David; Oh, Uhtaek; Vasko, Michael; Wilcox, George L.; Overland, Aaron C.; Vanderah, Todd W.; Spencer, Robert H.

In: Brain Research Reviews, Vol. 60, No. 1, 04.2009, p. 90-113.

Research output: Contribution to journalArticle

Stein, C, Clark, JD, Oh, U, Vasko, M, Wilcox, GL, Overland, AC, Vanderah, TW & Spencer, RH 2009, 'Peripheral mechanisms of pain and analgesia', Brain Research Reviews, vol. 60, no. 1, pp. 90-113. https://doi.org/10.1016/j.brainresrev.2008.12.017
Stein C, Clark JD, Oh U, Vasko M, Wilcox GL, Overland AC et al. Peripheral mechanisms of pain and analgesia. Brain Research Reviews. 2009 Apr;60(1):90-113. https://doi.org/10.1016/j.brainresrev.2008.12.017
Stein, Christoph ; Clark, J. David ; Oh, Uhtaek ; Vasko, Michael ; Wilcox, George L. ; Overland, Aaron C. ; Vanderah, Todd W. ; Spencer, Robert H. / Peripheral mechanisms of pain and analgesia. In: Brain Research Reviews. 2009 ; Vol. 60, No. 1. pp. 90-113.
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