Peripheral and central mechanisms of cutaneous hyperalgesia

Prog Neurobiol. 1992;38(4):397-421. doi: 10.1016/0301-0082(92)90027-c.

Abstract

Hyperalgesia after cutaneous injury can be divided into two phenomena: Primary hyperalgesia occurs at the site of injury and is characterized by hyperalgesia to mechanical and heat stimuli. Secondary hyperalgesia occurs outside the injury site and is characterized by mechanical hyperalgesia only. Hyperalgesia in inflammatory processes corresponds to primary hyperalgesia. Hyperalgesia in referred pain and neuropathic pain resembles secondary hyperalgesia (Table 3). Evidence for the latter would be strengthened if hyperalgesia to cooling stimuli, which is observed in neuropathic pain, was also demonstrated in referred pain and in secondary hyperalgesia. Some of the more likely neural mechanisms to explain primary and secondary hyperalgesia are illustrated in Fig. 8. Primary hyperalgesia to heat stimuli has a counterpart in the sensitization of peripheral nociceptors to heat stimuli (Fig. 8A), leading to similar changes in central neurons. In addition, the enlargement of the mechanical receptive field of primary afferent nociceptors to include the site of injury may account for the primary hyperalgesia to mechanical stimuli (Fig. 8B). In the literature, there are some contradictions with respect to the stimulus modalities to which hyperalgesia and sensitization occur. In spite of the well-documented sensitization of primary afferent nociceptors to heat stimuli, there are few studies on its molecular mechanisms. On the other hand, there is pharmacological evidence for a peripheral mechanism of primary mechanical hyperalgesia, but little direct evidence that nociceptors can be sensitized to mechanical stimuli by injury. This contradiction should spawn further investigations into the mechanical response properties of nociceptors and into the molecular mechanisms of heat sensitization. Secondary hyperalgesia to mechanical stimuli is likely due to the sensitization of central pain signalling neurons (CPSNs). This sensitization could involve only input from nociceptors (Fig. 8C), since mechanical pain thresholds after a cutaneous injury are of the same order as those of nociceptors. Central sensitization could also be the result of enhanced connectivity between low-threshold mechanoreceptors and CPSNs (Fig. 8D). This form of sensitization may account for the pain to light touch associated with neuropathic pain. Receptive field plasticity is a prevalent property of dorsal horn neurons and probably plays a vital role with regard to hyperalgesia. The molecular mechanisms of synaptic plasticity are currently subject to intense experimental investigation and may provide new insights on the mechanisms of pain and hyperalgesia.

Publication types

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

MeSH terms

  • Animals
  • Capsaicin / toxicity
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Mustard Plant
  • Nerve Fibers / physiology
  • Nerve Fibers, Myelinated / physiology
  • Neurons, Afferent / physiology
  • Nociceptors / physiopathology
  • Physical Stimulation
  • Plant Extracts / toxicity
  • Plant Oils
  • Rats
  • Skin / injuries
  • Skin / innervation
  • Skin Diseases / etiology
  • Skin Diseases / physiopathology*
  • Skin Temperature
  • Spinothalamic Tracts / physiopathology

Substances

  • Plant Extracts
  • Plant Oils
  • Capsaicin
  • mustard oil