Differential Alterations in Offset Analgesia and Conditioned Pain Modulation in Fibromyalgia: Evidence for Distinct Central Dysregulation

Eur J Pain. 2026 Mar;30(3):e70231. doi: 10.1002/ejp.70231.

ABSTRACT

BACKGROUND: Chronic pain often involves abnormalities in central pain processing. Two commonly used experimental methods for central pain modulation are conditioned pain modulation (CPM) and offset analgesia (OA). However, it is uncertain how similar the underlying processes they measure are. Here, we applied CPM and OA in patients with fibromyalgia, a model disease of central sensitization, to explore these questions further.

METHODS: Fifty-four female participants (27 fibromyalgia patients and 27 healthy participants) completed the Fibromyalgia Impact Questionnaire (FIQ) and the McGill questionnaire and underwent CPM and OA in a randomised order.

RESULTS: CPM and OA were positively correlated in healthy participants (R_s = 0.40, p = 0.03) but negatively correlated in patients (R_s = -0.47, p = 0.01). Additionally, we divided patients into responders and nonresponders for CPM and found that a significant negative correlation existed exclusively in nonresponders (R_s = -0.64, p = 0.02), whereas no correlation existed in responders. Furthermore, CPM in patients was positively correlated with FIQ (R_s = 0.4, p = 0.04) and McGill (R_s = 0.65, p = 0.003), whereas OA was negatively correlated with both FIQ (R_s = -0.445, p = 0.02) and McGill (R_s = -0.47, p = 0.03).

CONCLUSIONS: This study is the first to show that OA, not just CPM, is correlated with clinical features in fibromyalgia patients and that these two paradigms are inversely correlated and differentially related to disease symptomatology in fibromyalgia patients.

STATEMENT OF SIGNIFICANCE: This study is the first to demonstrate that conditioned pain modulation (CPM) and offset analgesia (OA) are inversely correlated in patients with fibromyalgia compared with healthy controls and show distinct associations with symptom severity. These findings reveal divergent mechanisms of central pain inhibition in chronic pain, highlighting the potential of both OA and CPM as novel markers for disease characterisation.

PMID:41784951 | DOI:10.1002/ejp.70231