Theoretical review: Altered pain regulatory systems in chronic pain

Stephen Bruehl*, James A. McCubbin, R. Norman Harden

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


This review synthesizes the existing literature regarding the relationship between resting blood pressure and pain sensitivity, and the literature indicating possible endogenous opioid dysfunction in chronic pain. Adaptive interactions between the cardiovascular and pain regulatory systems occur in healthy individuals, with greater blood pressure associated with decreased acute pain sensitivity. Endogenous opioids appear necessary for full expression of this relationship. There is ample evidence indicating diminished endogenous opioid CSF/plasma levels in chronic pain patients, yet little is known about the functional effects of these opioid changes. A theoretical model is proposed based upon the literature reviewed suggesting progressive dysfunction in endogenous opioid systems with increasing chronic pain duration. This dysfunction is hypothesized to result in dysregulation of normally adaptive relationships between the cardiovascular and pain regulatory systems, resulting in increased chronic pain intensity and increased acute pain sensitivity among chronic pain patients. Preliminary data are consistent with the hypothesis of progressive opioid changes resulting in dysfunctional alterations in the adaptive blood pressure-pain relationship. Clinical implications of this theory are discussed. Copyright (C) 1999 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)877-890
Number of pages14
JournalNeuroscience and Biobehavioral Reviews
Issue number6
StatePublished - Oct 1999


  • Blood pressure
  • Cardiovascular
  • Chronic pain
  • Endogenous opioids
  • Pain
  • Pain sensitivity

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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