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Trying to Parse True Meaning of Pain Can Be Challenging for Rheumatologists

Simon M. Helfgott, MD  |  Issue: March 2016  |  March 15, 2016

Responders showed significantly higher baseline activation in thalamic, limbic and associative areas of the brain than nonresponders. Moreover, brain activity decreased within three days after infliximab exposure in the responders, preceding clinical responses, which were first noted on Day 7, and responses observed on the anatomic hand MRI, which were noted on Day 28.

The authors raise the tantalizing question of whether the beneficial effects of anti-TNF therapy are initiated in the brain days before the synovium responds. Because we currently lack tests that predict response to costly biologic therapy, the authors ask whether fMRI results might be used to forecast the therapeutic success of cytokine-targeting therapies.6,7

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A second study demonstrated how the modification of behavior induced by chronic pain carries a distinct immunologic signature.8 In this study of rats that underwent sciatic nerve chronic constriction injury to create a model of chronic neuropathic pain, it was observed that one of three behaviors developed following the procedure. Rodents exhibited pain and disability behaviors, pain and transient disability or simply pain alone. Some just hobbled about their cages with variable degrees of success, and others lost their usually avid interest in dealing with intruders placed inside their habitat.

Strikingly, for each of these three behavioral attributes, a distinct immune signature developed that could be identified by analyzing specific cytokine levels in the sciatic nerve, the spinal cord and the dorsal root ganglia. These changes correlated with the degree of disability, suggesting that individual immune signatures played a significant role in determining the different behavioral trajectories following nerve injury, which in some cases led to persistent affective and motivational disturbances. Might this experiment mimic what we often observe in patients dealing with chronic pain?

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In the third study, mass cytometry—a highly parameterized single-cell-based platform that can determine functional responses in precisely phenotyped immune cell subsets—was used to comprehensively characterize phenotypic and functional alterations of the human immune system as they occurred in vivo in patients undergoing hip-joint arthroplasty.9 The primary aim was to extract “surgery” or “trauma-specific” immune signatures and to determine, secondarily, whether such signatures contain clinical correlates of surgical recovery.

The authors observed that by studying the cell signaling responses in less than 2% of subjects’ peripheral leukocytes, they were able to identify specific cell signaling responses, most notably in CD14+ monocytes, that accounted for between 40% and 60% of the variability in recovery rates. Similar to what was seen in the rodent study, these unique immune signatures correlated well with the levels of pain, fatigue and functional impairment that were measured six weeks postoperatively.

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Filed under:OpinionRheuminationsSpeak Out Rheum Tagged with:DiagnosisPainpatient carerheumatologistrheumatologyswelling

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