Conditioned pain modulation (CPM) as a biomarker of fibromyalgia and pain severity: effect of the CPM paradigm used

Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, although we did not observe any correlation between CPM measures and clinical symptoms, we found that patients with impaired CPM response displayed more severe symptoms, though less generalized pain. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.