Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study

Lancet. 2002 May 11;359(9318):1655-60. doi: 10.1016/S0140-6736(02)08589-6.


Background: Complex regional pain syndromes can be relieved by sympathetic blockage. The mechanisms of sympathetically maintained pain (SMP) are unclear. We aimed to establish the effect of physiological sympathetic cutaneous vasoconstrictor activity on pain and hyperalgesia in patients with complex regional pain syndromes.

Methods: High and low cutaneous vasoconstrictor activity was produced by whole-body cooling and warming (thermal suit) in 13 patients with type I disease and in ten controls. The degree of cutaneous vasoconstrictor discharge was monitored by measurement of skin blood flow and temperature at the arm and leg. Local skin temperature at the affected region was fixed at 35 degrees C. Pain was quantified during high and low cutaneous vasoconstrictor activity (intensity of spontaneous pain, area of mechanical hyperalgesias, heat-pain thresholds). Furthermore, pain was measured before and after diagnostic sympathetic blockage to identify patients with SMP and sympathetically independent pain.

Findings: In patients with SMP, intensity of spontaneous pain significantly increased, by 22%, and spatial distribution of mechanical dynamic and punctate hyperalgesia increased by 42% and 27%, respectively, during high sympathetic activity compared with low activity. Heat-pain thresholds did not differ during high and low cutaneous vasoconstrictor activity (cold and warm state, 43.6 degrees C vs 44.6 degrees C). Pain relief after sympathetic blockage correlated with augmentation of spontaneous pain after experimental stimulation of cutaneous vasoconstrictor activity (r=0.6, p=0.0244).

Interpretation: We have shown that in complex regional pain syndromes with SMP, physiological activation of cutaneous vasoconstrictor neurons projecting to the painful arm or leg enhances spontaneous pain and hyperalgesia. We postulate that there is a pathological interaction between sympathetic and afferent neurons within the skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Temperature
  • Case-Control Studies
  • Complex Regional Pain Syndromes / etiology
  • Complex Regional Pain Syndromes / physiopathology*
  • Complex Regional Pain Syndromes / prevention & control
  • Female
  • Humans
  • Hyperalgesia / etiology
  • Hyperalgesia / physiopathology*
  • Hyperalgesia / prevention & control
  • Male
  • Middle Aged
  • Pain Measurement
  • Statistics, Nonparametric
  • Sympathetic Nervous System / physiopathology*
  • Vasoconstriction