Central sensitization: Nice to know?

This issue publishes a paper by Arendt-Nielsen et al. entitled ‘Assessment and manifestation of central sensitization across different chronic pain conditions’ (Arendt-Nielsen et al., 2018). The authors have to be applauded for this very comprehensive work of measurements of central sensitization and their relevance to human pain conditions. Perhaps, central sensitization has been the most relevant advance of the last three decades in understanding the clinical pathophysiology of pain. Before this notion, the discrepancy between magnitude of tissue damage and severity of pain had hardly an explanation other than hysteria. While the scientific foundation of the influence of psychosocial factors was growing, central sensitization has provided a neurobiological basis for the central modulation of pain that had been postulated with the gate control theory. Both research lines have rectified the belief that pain simply results from the transmission of a noxious stimulus from a damaged tissue to the brain, while establishing the scientific foundation for central modulation of pain processes. Furthermore, they have validated a generation of patients who, otherwise, would have been left with no explanation for their symptoms, or even judged as malingers. Because central sensitization matters to patients, one may argue that it has to be measured. Several caveats apply to measuring central sensitization in humans. As Arendt-Nielsen et al. point out, most methods cannot access directly central nociceptive processes. Therefore, even the term ‘central sensitization’ is problematic when used for human pain. Independent of the virtues and vices of the assessment methods, the fact that central sensitization is relevant for patients is not a strong reason to measure it. On one side, detecting central sensitization may provide patients with an explanation for their symptoms, which is valuable. On the other hand, both patients and health care providers have the legitimate wish to use this information to improve outcomes. The essential question is: once we measure central sensitization, what then? One area of potential application if prognosis. The paper by Arendt-Nielsen et al. discusses studies showing that central sensitization predicts adverse outcomes, such as persisting pain after surgery. However, the results are not consistent across studies. Some of them have not found measures of sensitization to predict persisting pain. Positive studies have typically used multiple assessment methods, with only a subset of them being predictive. Therefore, there are concerns of potential false-positive results due to multiple testing. Within positive studies, there is no consistency as to which assessment modalities predict persisting pain, raising further concerns on the external validity of the findings. Importantly, statistically significant associations do not imply clinical usefulness. For a test to support clinical decision making, it has to have acceptable sensitivity, specificity and likelihood ratios. Unfortunately, these parameters have rarely been assessed. In the light of the complexity of chronic pain, they are unlikely good enough to allow clinical decisions with an acceptable confidence. Another area of interest is predicting the efficacy of treatments. The question is whether central sensitization makes patients more or less likely to respond to specific treatments. This has also been an area of recent research, as discussed in the paper by ArendtNielsen et al. Again, the results of studies have been inconsistent. To the best of the author’s knowledge, there are no adequately powered investigations that have found acceptable sensitivity, specificity and likelihood ratios of measures of central sensitization for the prediction of treatment efficacy. The notion of central sensitization is essential for our understanding of clinical pain. However, we cannot yet use this knowledge to meet patients’ expectation of improving their life. We do not have