Abstract
Non-invasive functional brain imaging is used more than ever to investigate pain in health and disease, with the prospect of finding new means to alleviate pain and improve patient wellbeing. The observation that several brain areas are activated by transient painful stimuli, and that the magnitude of this activity is often graded with pain intensity, has prompted researchers to extract features of brain activity that could serve as biomarkers to measure pain objectively. However, most of the brain responses observed when pain is present can also be observed when pain is absent. For example, similar brain responses can be elicited by salient but non-painful auditory, tactile and visual stimuli, and such responses can even be recorded in patients with congenital analgesia. Thus, as argued in this review, there is still disagreement on the degree to which current measures of brain activity exactly relate to pain. Furthermore, whether more recent analysis techniques can be used to identify distributed patterns of brain activity specific for pain can be only warranted using carefully designed control conditions. On a more general level, the clinical utility of current pain biomarkers derived from human functional neuroimaging appears to be overstated, and evidence for their efficacy in real-life clinical conditions is scarce. Rather than searching for biomarkers of pain perception, several researchers are developing biomarkers to achieve mechanism-based stratification of pain conditions, predict response to medication and offer personalized treatments. Initial results with promising clinical perspectives need to be further tested for replicability and generalizability.
Highlights
Physical pain is intrinsically unpleasant and aversive
We argue that the attempts to falsify the hypothesis that the brain responses being measured are specific for pain using appropriate control stimuli have been insufficient, and the liberal use of terms implying specificity has biased the interpretation of several pain neuroimaging results
We argue that the terms pain-specific or nociceptive-specific should be avoided because it is practically impossible to demonstrate specificity, and because it is more informative to approach the problem in probabilistic terms and try to assess the likelihood that a given response is preferential for pain, i.e. its selectivity
Summary
Physical pain is intrinsically unpleasant and aversive. This is the very reason why it is advantageous for survival: it drives behaviours that avoid bodily injury when interacting with the environment. When assessing the selectivity or specificity for pain of a given brain response, it is crucial to use non-painful control stimuli that elicit sensations matched with respect to unpleasantness, salience and relevance.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
