Is nociceptor activation by alpha-1 adrenoreceptors the culprit in sympathetically maintained pain?

Research output: Contribution to journalArticlepeer-review


In certain patients, pain depends on sympathetic activity in the affected area. Sometimes referred to as reflex sympathetic dystrophy or causalgia, this disease is termed sympathetically maintained pain (SMP). Several lines of evidence support the hypothesis that in this disease alpha-1 adrenoreceptors develop in peripheral tissues (possibly at terminals of nociceptors), such that the release of norepinephrine from the sympathetic terminals activates the nociceptors and leads to the sensation of pain. This hypothesis stems from previous work with regional guanethidine block, stimulation of sympathetic ganglia, application of norepinephrine to the affected area, and oral sympatholytic drugs. Recent results from alpha-adrenergic agonists and antagonists in patients with and with-out SMP support this hypothesis. Intravenous phentolamine, a short-acting, competitive alpha-adrenergic antagonist, produced pain relief that was highly correlated with relief obtained with a local anesthetic block of the sympathetic ganglia. This experiment supports the contention that SMP is mediated by an alpha-adrenoreceptor. Topical application of the alpha-2 agonist, clonidine, relieved hyperalgesia at the site of application presumably by reducing the release of norepinephrine. Injection of norepinephrine and the alpha-1 agonist phenylephrine into the clonidine-treated area produced marked pain and hyperalgesia. These results implicate the alpha-1 adrenoreceptor as the culprit in SMP.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalAPS Journal
Issue number1
StatePublished - 1992
Externally publishedYes


  • adrenoreceptors
  • allodynia
  • alpha-adrenoreceptor
  • causalgia
  • clonidine
  • human
  • hyperalgesia
  • nociceptors
  • phetolamine
  • reflex sympathetic dystrophy
  • sympathetic blocking agents
  • sympathetic nervous system

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


Dive into the research topics of 'Is nociceptor activation by alpha-1 adrenoreceptors the culprit in sympathetically maintained pain?'. Together they form a unique fingerprint.

Cite this