A possible neural basis for stress-induced hyperalgesia

Melissa E. Martenson, Justin S. Cetas, Mary M. Heinricher

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Intense stress and fear have long been known to give rise to a suppression of pain termed "stress-induced analgesia", mediated by brainstem pain-modulating circuitry, including pain-inhibiting neurons of the rostral ventromedial medulla. However, stress does not invariably suppress pain, and indeed, may exacerbate it. Although there is a growing support for the idea of "stress-induced hyperalgesia", the neurobiological basis for this effect remains almost entirely unknown. Using simultaneous single-cell recording and functional analysis, we show here that stimulation of the dorsomedial nucleus of the hypothalamus, known to be a critical component of central mechanisms mediating neuroendocrine, cardiovascular and thermogenic responses to mild or "emotional" stressors such as air puff, also triggers thermal hyperalgesia by recruiting pain-facilitating neurons, "ON-cells", in the rostral ventromedial medulla. Activity of identified RVM ON-cells, OFF-cells and NEUTRAL cells, nociceptive withdrawal thresholds, rectal temperature, and heart rate were recorded in lightly anesthetized rats. In addition to the expected increases in body temperature and heart rate, disinhibition of the DMH induced a robust activation of ON-cells, suppression of OFF-cell firing and behavioral hyperalgesia. Blocking ON-cell activation prevented hyperalgesia, but did not interfere with DMH-induced thermogenesis or tachycardia, pointing to differentiation of neural substrates for autonomic and nociceptive modulation within the RVM. These data demonstrate a top-down activation of brainstem pain-facilitating neurons, and suggest a possible neural circuit for stress-induced hyperalgesia.

Original languageEnglish (US)
Pages (from-to)236-244
Number of pages9
JournalPain
Volume142
Issue number3
DOIs
StatePublished - Apr 2009

Keywords

  • Brainstem
  • Hyperalgesia
  • OFF-cells
  • ON-cells
  • Pain-modulation
  • Rostral ventromedial medulla

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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