Pain referral area is reduced by remote pain

Eur J Pain. 2021 Sep;25(8):1804-1814. doi: 10.1002/ejp.1792. Epub 2021 Jun 3.


Background: Endogenous pain inhibitory mechanisms are known to reduce pain intensity, but whether they influence the size and distribution of pain referral is unclear. This study aimed to determine if referred pain is reduced by applying a remote, conditioning painful stimulus.

Methods: Twenty-four healthy men participated in this randomized, crossover study with a control and conditioning session. Referred pain was induced from the infraspinatus muscle (dominant side) by a painful pressure for 60 s. When applying pressure, the intensity was adjusted to a local pain intensity of 7/10 on a numerical rating scale. In the conditioning session, tonic painful pressure was simultaneously applied to the non-dominant leg during induction of referred pain. The area of referred pain was drawn onto a digital body chart and size extracted for data analysis.

Results: For the total group and in a subgroup with distinct patterns of referred pain (n = 15/24), the pain area perceived in the back and front+back was smaller during the conditioning compared with the control (p < 0.05). No significant difference was found between sessions in a subgroup only demonstrating local pain (n = 9/24).

Conclusions: Engaging the descending noxious inhibitory control reduced the size of pain areas predominately when distinct pain referral was present. Assuming a conditioning effect of descending inhibitory control acting on dorsal horn neurons, these findings may indicate that mechanisms underlying pain referral can be modulated by endogenous control. The findings may indicate that referred pain may be a useful proxy to evaluate sensitivity of central pain mechanisms as previously suggested.

Significance: The current results indicate a link between endogenous inhibition and pain referral. Descending inhibitory control effects on pain referral support a spinal mechanism involved in pain referral. Future studies should investigate whether the spatial characteristics of referred pain (e.g. size, frequency of affected body regions and distribution away from the primary nociceptive stimulus) can useful to evaluate the efficiency of endogenous pain modulation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Over Studies
  • Humans
  • Male
  • Pain Measurement
  • Pain Threshold*
  • Pain*
  • Referral and Consultation