This study is interesting because it attempts to elucidate the cause of residual pain in patients with radiographic axial spondyloarthritis, treated with biologics, for at least 3 months. The authors evaluate nociplastic pain and neuropathic pain, using questionnaires that are partially validated to discriminate these types of pain. This concept is important because the behaviour in the face of residual pain should be different if this pain has a non-inflammatory cause, and it could avoid unnecessary biological changes in these patients. The authors found a probable nociceptive or neuropathic component in a low percentage of patients, and a somewhat higher percentage if it is considered a possible diagnosis. These percentages were higher in patients who maintained residual pain, measured by the activity indices used in axial spondyloarthritis: ASDAS and BASDAI. This could indicate that perhaps this residual pain is due to this type of pain that is not caused by inflammation. However, this study has many limitations. Firstly, the patients had an established disease with many years (11) of evolution, so it is possible that they had damage as a cause of pain. The number of patients was low, and it is not absolutely clear how long after starting the biologics the evaluation was carried out (more than three months). On the other hand, there is no baseline measurement before treatment, so we cannot know whether the patients improved their neuropathic and nociceptive pain or not. Finally, and very importantly, we do not know if there was residual inflammatory activity on the MRI that could explain the residual activity, and explain the results of the questionnaires. We cannot be sure that these questionnaires applied to patients with spondyloarthritis are not also measuring inflammation. The proposal is interesting, but requires more studies to obtain definitive conclusions.
This report is important because it attempts to demonstrate that there are different sources of persisting pain, which may be unrelated to inflammation, in patients after a 3-month course of treatment with bioDMARDs for axSpA. In particular, the authors attempt to use the International Association for the Study of Pain (IASP) framework for conceptualizing pain into 3 categories: nociceptive, neuropathic, and nociplastic. The latter is defined by pain that is not associated with abnormalities of neural or non-neural tissue. This and other studies suggest that this is an important contributor to pain in a substantial proportion of patients with axSpA and it is unknown if such pain is amenable to therapeutic intervention with existing treatments. A major caveat with interpretation of this and other studies in axSpA is the lack of information from MRI evaluation, which could demonstrate persistent inflammation as a basis for pain. It has been well-established that MRI features of inflammation correlate poorly with the ASDAS and BASDAI in patients with established axSpA. The study also did not mention if patients had concomitant degenerative spinal disease, which could also account for persisting pain. Further study of nociplastic pain in axSpA might include more objective techniques such Quantitative Sensory Testing (QST) to assess hyperalgesia, Temporal Summation (TS) testing, which assesses the increased pain perception in response to repetitive noxious stimuli, and Conditioned Pain Modulation (CPM), which assesses the reduction in pain sensitivity of a tested stimulus due to the interference of a second stimulus (conditioning stimulus) applied at the same time but to a remote body region.