Vagal afferent modulation of nociception

Brain Res Brain Res Rev. May-Aug 1992;17(2):77-99. doi: 10.1016/0165-0173(92)90009-b.


Chemical, electrical or physiological activation of cardiopulmonary vagal (cervical, thoracic or cardiac), diaphragmatic vagal (DVAG) or subdiaphragmatic vagal (SDVAG) afferents can result in either facilitation or inhibition of nociception in some species. In the rat, these effects depend upon vagal afferent input to the NTS and subsequent CNS relays, primarily in the NRM and ventral LC/SC, although specific relay nuclei vary as a function of the vagal challenge stimulus. Spinal pathways and neurotransmitters have been identified for vagally mediated effects on nociception and consistently implicate the involvement of descending 5-HT and noradrenergic systems, as well as intrinsic spinal opioid receptors. Species differences may exist with respect to both the effects of DVAG and SDVAG afferents on nociception and the efficacy of vagal afferents to modulate nociception. However, it is also possible that such differences reflect the modality of noxious input (e.g., visceral versus cutaneous), the type of neuronal activity investigated (e.g., resting versus noxious-evoked), spinal location of recording (e.g., thoracic versus lumbosacral) and/or parameters of stimulation. It is also possible that activation of some vagal afferents is aversive, but whether this contributes to changes in nociception produced by vagal activation has not clearly been established. Finally, the vagal-nociceptive networks described in this review provide a fertile area for future study. These networks can provide an understanding of physiological and pathophysiological peripheral events that affect nociception.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Afferent Pathways / physiology*
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Brain / physiology
  • Diaphragm / innervation
  • Electric Stimulation
  • Enkephalin, Methionine / analogs & derivatives
  • Enkephalin, Methionine / pharmacology
  • Macaca fascicularis
  • Morphine / pharmacology
  • Nociceptors / drug effects
  • Nociceptors / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Serotonin / pharmacology
  • Spinal Cord / physiology
  • Synaptic Transmission
  • Vagus Nerve / physiology*


  • Serotonin
  • Enkephalin, Methionine
  • enkephalinamide-Met, Ala(2)-
  • Morphine