Acute pain mechanisms

Surg Clin North Am. 1999 Apr;79(2):213-29. doi: 10.1016/s0039-6109(05)70380-7.

Abstract

The systems activated by tissue-injuring stimuli are complex. The nociceptive primary afferents have little spontaneous activity under normal conditions; however, after tissue injury, they display longlasting, ongoing activity. This results, in part, because the injury elicits the release of active factors that sensitize or excite the peripheral nerve terminal. A threshold that is lowered to the extent that body temperature and the pressure of edema are adequate stimuli results in spontaneous pain. This phenomenon is mediated by a variety of blood-borne active factors released during plasma extravasation, by agents released from local inflammatory cells, and by neurotransmitters released from the peripheral terminals of the primary afferent fibers themselves. Well-defined projections into the dorsal horn convey the "pain message" to at least two well-defined populations of neurons: those that are nociceptive specific and those that display an intensity-linked discharge over a range of stimuli from innocuous to noxious. Convergence from various fiber types, modalities, and end organs permits the encoding of afferent traffic with respect to intensity and location. The convergence of axons from somatic and visceral structures reflects the mechanism for the so-called "referred pain state." Most importantly, these dorsal horn systems have a dynamic component in addition to the hard-wiring; their output can be regulated both up and down. The up-regulation provides the basis for much of the facilitated processing that is believed to account for a significant percentage of the postinjury pain state. The facilitated state has a unique pharmacology, with the underlying mechanisms reflecting a cascade of actions that starts with the NMDA receptor and proceeds through the spinal release of intermediaries, such as prostaglandins and nitric oxide. Conversely, the ability to down-regulate the dorsal horn stimulus response function accounts for the powerful control exerted by a wide variety of diverse factors, including the spinal delivery of opioid and nonopioid analgesics and the "endogenous analgesia system." These linkages reflect the complexity of the encoding mechanisms that transduce the tissue injury into the behavioral sequela known as pain. This article also emphasizes that, although considerable progress has been made in the past decade, the current pace of research promises greater insights.

Publication types

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

MeSH terms

  • Afferent Pathways / physiology
  • Animals
  • Autonomic Nervous System / physiology
  • Humans
  • Neurotransmitter Agents / pharmacology*
  • Nociceptors / physiology*
  • Pain / physiopathology*
  • Pain Threshold
  • Pain, Postoperative / physiopathology
  • Spinal Cord / cytology
  • Spinal Cord / physiology

Substances

  • Neurotransmitter Agents