Nature | Editorial

Fifty shades of pain

Measuring hurt is harder than inflicting it.

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Science has produced such a bewildering array of tools and techniques to cause gentle pain that to list them all can seem like describing a torture chamber in Toytown. To study the body’s responses, people are prodded with fingers, pricked with needles and pressed with ice. Toes are squeezed and ear lobes pinched. Muscles can be poked with sticks and zapped with electricity. Mustard oil is spread on the skin and capsaicin injected beneath it. Laser pulses offer a double hit: an initial prick followed by a burning sensation.

When properly performed, these human experimental pain models help researchers to understand both the mechanisms of pain and the effectiveness of new compounds that could help to relieve it. The translational bridge from animal experiments to human trials is built on the backs of countless volunteers who sign up for a little lab-based agony. (Special thanks indeed must go to the anonymous 18 brave souls who had “two series of rectal balloon distensions performed on two separate days” to help to study “cortical processing of visceral sensations and pain” (D. Lelic et al. Neurogastroenterol. Motil. 27, 832–840; 2015).)

Similar studies check on the pain caused by fully inflating a balloon inside other internal organs. Although, as a review of these pain models noted in 2012, it is (perhaps counter-intuitively) more difficult to find people who are willing to take such balloons through the mouth to stretch the oesophagus: “Difficulties in tolerating balloon distension commonly results in poor recruitment rates as well as the potential for esophageal perforation” (K. S. Reddy et al. J. Res. Med. Sci. 17, 587–595; 2012).

When it comes to assessing, measuring and reducing pain, the science toolbox is less well stocked. We have thankfully moved on from the earnest 1950s debates about how the pain tolerance of patients was linked to eye colour — discussions that were themselves coloured by racism. But there is much about pain that we still do not realize, and important knowledge remains beyond the reach of even the best-placed balloon.

Some of what we do know is presented this week in an Outlook supplement. A series of articles describes the physical, neurological and psychological factors that seem to contribute, and offers a snapshot of current thinking on the best forms of relief.

Science and medicine no longer use a person’s ethnicity and religion to mark how well they will tolerate the pain of a procedure, but equally, researchers have not yet found a reliable way to measure pain tolerance. The search for quantifiable ways to compare painful sensations, and to diagnose pain in those who are unable to communicate it, mirrors the effort in psychiatric research to find useful biomarkers for mental-health disorders.

For pain, expression of inflammatory mediators in the blood and the presence of metabolites in saliva could be biological guides to a person’s distress. So, too, could brain scans that reveal the neural signature of chronic pain. However, as Nature pointed out last year, such techniques must be introduced with care, not least because they could be used by insurance companies and others to demand ‘proof’ of pain as a way to overrule reported personal experience.

Science has already developed some weird and wonderful ways to deliberately cause pain. It should be wary that it does not inadvertently create some more.

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