Are blood vessels secret players in pain?

The level of pain that you'd feel after being poked, or having a wound attended to, can be affected by all kinds of factors. Playing a distracting VR game can reduce pain substantially, for example, as can hypnosis.

Some studies have found that even limb position can make a difference, too. If one hand has been hurt, crossing the arms in front of the body can alleviate that pain. It's thought this is because it impedes the brain's normal processes for working out the precise location of bodily damage.

Now, in a paper in the European Journal of Pain, a team led by Arthur S. Courtin at UCLouvain in Belgium report a new finding in this area. They find that if one arm is hurting, lifting it up into the air can make the pain worse — an effect that is seemingly modulated by gravity's effect on blood vessels, and which could open doors to better understanding how we experience pain.

The study was prompted by an accidental observation while the group piloted some research on the time-course of sensations caused by the application of capsaicin, the 'hot' ingredient in chilli peppers. As expected, applying capsaicin to participants' arms triggered 'burning' pain. But, one volunteer also reported that after casually placing her hands "behind her head, the pain — which had faded — suddenly flared up, becoming excruciating."

In an attempt to replicate this strange observation, the team recruited 20 healthy volunteers. While ten lay down flat, and the other ten sat up, they had a patch applied to each of their forearms. One patch contained capsaicin; the other did not. These patches were left on for about an hour. Before, during and after the patches were applied, the participants reported on sensations in their arms. They did this both while their arms were at rest, horizontal to the ground, and when they were raised into a vertical position.

As expected, the capsaicin-free patch triggered virtually no sensations, whether the arm was horizontal or vertical. But for the capsaicin-treated arm, the participants reported strong 'burning hot' sensations that quickly increased after the patch was applied, plateaued after around 20 minutes and then slowly declined. However, raising this treated arm "produced a clear augmentation of these burning sensations", the team reports.

As body position — laying flat or sitting up — didn't change this arm-raising effect, the team suspects that, in this case, the impact on pain was due to the effects of gravity, rather than changes in limb position in relation to the rest of the body. So, what effects, exactly?

The team doesn't know for sure. But, they note that when we raise an arm in the air, much of the blood inside it rapidly drains down, in the direction of gravity. This causes a drop in local blood pressure, and this triggers the veins to dilate. It's possible, they suggest, that this sensitises nociceptors (damage detectors) in and around the veins, increasing feelings of pain.

This theory is supported by their observations that pain when the arm was raised "felt deeper and more widespread than when the arm was at rest". Also, pain in this context had a "sharp, stabbing and pulsatile quality". These observations tally with descriptions of the pain triggered by stimulation of veins, they write.

This study wasn't designed to explore whether pain from other causes would also get worse if the arm was raised, or how vascular changes might influence pain perceptions in other parts of the body, such as the feet. Further work exploring this unexpected phenomenon, however, could provide new insights into factors which exacerbate (or alleviate) pain sensations.

Read the paper in full:
Courtin, A. S., Knaepen, C., Mouraux, A., & van Neerven, S. G. A. (2024). Effect of limb position change on capsaicin‐evoked pain: Evidence of interplays between the vascular and nociceptive systems? European Journal of Pain. https://doi.org/10.1002/ejp.4742

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