Is central sensitization relevant in acute low back pain?

Abstract

In this issue of the European Journal of Pain, a study by Chung et al. found no evidence for central sensitization in patients with acute low back pain, as compared with a group of pain-free individuals (Chang et al., 2022). A subgroup of patients displayed features of central sensitization with pressure and heat stimulation, as well as deficient conditioned pain modulation. However, pain severity and disability did not differ between this subgroup and the one that did not have features of central sensitization. These findings may sound surprising and in contrast with our current knowledge of mechanisms of pain. Acute low back pain is very prevalent, but resolves in most cases. Why does low back pain resolve in certain individuals, and not in other ones? This questions remains open despite decades of research. We have not been able to identify structural damages of the low back that reliably explain long-term pain. Demographic, clinical and psychosocial characteristics predict long-term low back pain, but do not explain a large proportion of the variability. The knowledge of neuroplasticity has greatly expanded our understanding of pathophysiology and generated an intriguing hypothesis: in some individuals, a new onset of low back pain would induce functional and structural changes in neural pathways, leading to augmentation of nociceptive processes and impairment in endogenous inhibition. These phenomena have received the umbrella term of “central sensitization”. Central sensitization would cause pain with limited, if any, nociceptive input from low back structures, thereby contributing to persistent pain. Has this hypothesis been confirmed by human research? Regrettably, studies on the association between indices of central sensitization and outcomes of low back pain have yielded inconsistent results. Groups of patients with acute low back pain, compared with groups of healthy controls, may display features of central sensitization, but studies have not converged to uniformly reproducible results. Most longitudinal studies on the prognostic value of indices of central sensitization in acute low back pain found either no or weak associations with long-term pain (Muller et al., 2019). As the results by Chang et al. suggest, displaying signs of central sensitization may not be associated with severity of acute low back pain and disability (Chang et al., 2022), a finding confirmed recently in lumbar radiculopathy (Huysmans et al., 2022). How do we explain the disappointing results? One explanation is that central sensitization does not occur in a significant manner in most patients with acute low back pain. While basic science has overwhelmingly demonstrated that acute injuries induce central sensitization, we do not have sensitive and specific diagnostic tools to detect pain-relevant injuries in acute low back pain. The development of central sensitization could be detected if measures were available before the onset of back pain. An increase in measures of central sensitization before-after the acute low back pain episode may tell us whether central sensitization is induced in individual patients, and whether this induction is a relevant predictor of long-term pain. Because acute low back pain is unpredictable, measures are done only after the onset of low back pain. Assessments after the onset of low back pain may be less predictive than before-after changes in indices of central sensitization. Human research relies on surrogate measures of central sensitization, mainly in the domain of quantitative sensory testing (QST) (Quesada et al., 2021). QST for musculoskeletal pain assesses primarily pain sensitivity, and assume that pain sensitivity reflects central sensitization. On the other hand, central sensitization is the result of multiple mechanisms, such as nociceptor sensitization, events at the first synapse, neuroinflammatory processes, and systemic immunomodulatory processes, among others. Our current measures do not allow the detection of specific mechanisms of central sensitization potentially associated with long-term pain, and rather reflect “umbrella” phenomena, such as enhanced pain sensitivity. Current methods may therefore be poor measures of central sensitization, and could rather reflect a constitutional hypersensitivity to sensory stimuli with limited clinical relevance. The likely inadequacy of current measures is confirmed by the inconsistent association with patient-reported outcomes (Chang et al., 2022; Huysmans et al., 2022). In conclusion, the importance of central sensitization as contributor to acute low back pain and predictor of persistent back pain remains uncertain. Current measures have at best modest prognostic value, and their clinical usefulness is questionable. Human measures of distinct mechanisms related to central sensitization would tell us which central modulatory processes are associated with persistent pain, and whether such processes might be targeted by therapeutics. Finally, in pain medicine one size rarely fits all. Processes related to central sensitization will unlikely be clinically relevant for all patients. The development of methods that detect outcome-relevant mechanisms of central sensitization at individual level will render the knowledge of central sensitization useful for personalized medicine. Supported by the University of Washington Clinical Learning, Evidence And Research (CLEAR) Center for Musculoskeletal Research. CLEAR is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (Award Number P30 AR072572-06/A168920). None.