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CPM procedures used in the study. All the participants underwent both paradigms in counterbalanced order.
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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...
Citations
... Neuropathic pain from various causes, such as chemotherapyinduced neuropathy [43] and spinal cord injury [44], has been associated with less efficient CPM. Patients with fibromyalgia present abnormalities in muscles or joints that are accompanied by severe pain and abnormal CPM [35,45]. Studies involving patients with osteoarthritis demonstrated that CPM is also lost in this condition [36,38,46]. ...
Diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, is a paradigm wherein the heterotopic application of a noxious stimulus results in the attenuation of another spatially distant noxious input. The pre-clinical and clinical studies show the involvement of several neurochemical systems in DNIC/CPM and point to a major contribution of the noradrenergic, serotonergic, and opioidergic systems. Here, we thoroughly review the latest data on the monoaminergic and opioidergic studies, focusing particularly on pre-clinical models of chronic pain. We also conduct an in-depth analysis of these systems by integrating the available data with the descending pain modulatory circuits and the neurochemical systems therein to bring light to the mechanisms involved in the regulation of DNIC. The most recent data suggest that DNIC may have a dual outcome encompassing not only analgesic effects but also hyperalgesic effects. This duality might be explained by the underlying circuitry and the receptor subtypes involved therein. Acknowledging this duality might contribute to validating the prognostic nature of the paradigm. Additionally, DNIC/CPM may serve as a robust paradigm with predictive value for guiding pain treatment through more effective targeting of descending pain modulation.
... Interestingly, our findings indicate that high alpha oscillations are linked to a lower CPM response, with statistical significance only on the right-hand side. This relationship can be explained by the role of alpha oscillations in modulating cortical excitability and sensory processing, which are essential for the brain's ability to regulate and inhibit pain; as shown in our CPM metric, a reduced CPM means a worse response to pain [10,49,50]. Additionally, the negative association between the alpha band in the parietal region and sleepiness illustrates the role of alpha activity in cognitive function, fatigue, and attention levels, as described previously in our study [24]. ...
These authors contributed equally to this work. Abstract: Background: Spinal cord injury (SCI) affects approximately 250,000 to 500,000 individuals annually. Current therapeutic interventions predominantly focus on mitigating the impact of physical and neurological impairments, with limited functional recovery observed in many patients. Electroen-cephalogram (EEG) oscillations have been investigated in this context of rehabilitation to identify effective markers for optimizing rehabilitation treatments. Methods: We performed an exploratory cross-sectional study assessing the baseline EEG resting state of 86 participants with SCI as part of the Deficit of Inhibitory as a Marker of Neuroplasticity in Rehabilitation Cohort Study (DEFINE). Results: Our multivariate models demonstrated a positive correlation between frontal delta asymmetry and depression symptoms, while the frontal alpha asymmetry band and anxiety symptoms were negatively correlated. Theta oscillations were negatively associated with motor-evoked potential (MEP), whereas alpha oscillations were positively associated with MEP in all regions of interest and with CPM response as a negative correlation. Based on the potential role of lower-frequency oscillations in exerting a salutogenic compensatory effect, detrimental clinical and neurophysiological markers, such as depression and lower ME, likely induce slow oscillatory rhythms. Alpha oscillations may indicate a more salutogenic state, often associated with various cognitive functions, such as attention and memory processing. Conclusions: These results show an attempt by the CNS to reorganize and restore function despite the disruption caused by SCI. Indeed, this finding also challenges the notion that low-frequency EEG rhythms are associated with cortical lesions. These results may contribute to the development of rehabilitation strategies and potentially improve the clinical outcomes of patients with SCI.
... This variability includes differences in the type of conditioning stimulus applied-such as thermal, mechanical, or pressure-based stimuli-as well as the specific anatomical region targeted for the stimulus or the application time. Moreover, responses to the CPM paradigm among FMS patients are inconsistent; while some FMS patients demonstrate a response to the conditioning stimulus, others show little to no response, indicating a range of individual differences in pain modulation among this population [16]. ...
Background/Objectives: Fibromyalgia syndrome (FMS) is a multifactorial pain syndrome not only characterized by widespread pain as the primary symptom but also accompanied by physical, psychological, and cognitive manifestations. Impairments in conditioned pain modulation (CPM) are common in this population; however, there is significant heterogeneity in the CPM response among women with FMS. The Left/Right Judgment Task (LRJT) is a validated method for studying motor imagery in chronic pain patients. Previous scientific evidence has not yet thoroughly investigated the relationship between CPM alterations and motor imagery processes in FMS patients. The aim of this study was to investigate the relationship between CPM and motor imagery. Methods: This is a secondary analysis of a cross-sectional study. Pain intensity (NPRS), disability (FIQ), mechanical hyperalgesia (PPT), descending pain modulation (CPM), and laterality discrimination (LRJT) were assessed in 30 women diagnosed with FMS. Participants were divided into two groups, responder and non-responder, according to their response to the CPM test. Results: Findings showed that the FMS subgroup of non-responders to CPM, performed worse in motor imagery processes (LRJT). Additionally, older age and higher mechanical hyperalgesia were also associated with poorer functioning of the inhibitory system. Conclusions: Women with FMS who are non-responders to CPM exhibit a reduced ability to perform motor imagery processes. Additionally, the non-responder group shown significant differences, such as older age and greater initial mechanical hyperalgesia compared to the responder group.
... In relation to the correlation between CPM and clinical status, our findings align with the recent study by Gil-Ugidos et al. [43] concerning CPM measurements using the ischemic pressure conditioning stimulus and the correlation with the FIQ and NPRS questionnaires. However, their study did not evaluate CPM using the cold pressor conditioning stimulus. ...
Background/Objectives: Fibromyalgia (FM) is a syndrome characterized by widespread chronic pain as the primary symptom. Neurophysiological pain mechanisms, such as the function of the descending inhibitory system, are impaired in this condition. The main objective of this study was to compare the results of two paradigms to evaluate CPM in women with FM. The secondary objective was to correlate the results of each CPM paradigm with the clinical status of patients with FM. Methods: One hundred and three FM women were divided into two groups: fifty patients diagnosed with FM were assigned to the conditioned pain modulation (CPM) group using a cold pressor stimulus, and fifty-three patients were assigned to the CPM group using the ischemic pressure stimulus. The main outcome measures were pain intensity, disability, mechanical hyperalgesia, and CPM. Results: The primary analysis revealed significant differences between the results obtained from the different CPM protocols. Poorer outcomes in the cold pressor test correlated with higher pain intensity and a greater disability index. Conclusions: Pain modulation abnormalities in FM patients were evident when using either the cold pressor or ischemic pressure stimuli to establish the CPM paradigm. The cold pressor conditioning stimulus elicited a stronger response than the ischemic pressure stimulus in FM patients.
Background
Amputation leads to significant physical, psychological, and emotional challenges, with chronic pain being among the most debilitating outcomes. Conditioned Pain Modulation (CPM) is a key mechanism for understanding pain modulation reflecting the central nervous system’s capacity to regulate pain.
Objective
This study aimed to evaluate CPM in amputees, comparing CPM between the amputated and non-amputated sides, and to identify factors influencing CPM in this population.
Method
Eighty-six amputees participated in the study. Sociodemographic and pain-related variables, including age, occupation, smoking status, pre-amputation pain duration, phantom limb pain, and pressure pain threshold, were assessed. Multiple linear regression models were performed to explore factors associated with CPM on both sides, with additional t -tests to compare CPM values between sides.
Results
The multivariate model for the amputated side explained 26.3% of CPM variability, with significant associations found for pre-amputation pain duration and retirement status, as well as PPT mean of the amputated side, smoking, and phantom limb pain and age. In contrast, the non-amputated side model explained 26.5% (Adjusted R-squared) of the variability, with the following significant variables: duration of pre-amputation pain (negative correlation), smoking history, phantom limb pain (negative correlation), and frequency of telescoping sensation (negative correlation). There were no significant differences in CPM between amputated and non-amputated sides ( p > 0.05).
Conclusion
The findings suggest that CPM on the amputated side is more influenced by pain experience and sociodemographic variables, while the non-amputated side shows less variability and is more resilient to these influences.
Background/Objectives: Quantitative sensory testing (QST) is one of the most reliable methods for assessing Fibromyalgia Syndrome (FMS). Despite its importance, there are still controversies regarding the correct interpretation of evoked responses, as they may vary depending on the protocol, individual characteristics, disease severity, and other factors. This study aims to examine how QST has been applied as an outcome measure in FMS. Methods: We considered three databases (Medline, Embase, and Web of Science) until June 2024. From a total of 2512 studies, 126 (39 RCTs and 87 non-RCTs) were selected for full reading after assessment for risk of bias and eligibility criteria. These criteria included at least one type of QST and a clear diagnosis of fibromyalgia (FMS). Results: The results highlighted a lack of standardization in QST, as no reported protocols were followed and there was no specific number of tender points tested for FMS. Additionally, there was inconsistency in the selection of sites and types of tests conducted. Conclusions: This heterogeneity in methodology may affect the comparability and interpretation of results, underscoring the urgent need for standardized guidelines for conducting QST in fibromyalgia studies. A clear understanding of how QST has been measured could prompt a reevaluation of current approaches to FMS assessment, leading to more accurate interpretations and, ultimately, improved management of this complex condition.
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. 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 randomized order. CPM and OA were positively correlated in healthy participants (R s = 0.405, P = 0.03) but negatively correlated in patients (R s =-0.478, 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 =-0.57, P = 0.03), whereas no correlation existed in responders. Furthermore, CPM in patients was positively correlated with FIQ (R s = 0.403, P = 0.04) and McGill (R s = 0.47, P = 0.04), whereas OA was negatively correlated with both FIQ (R s =-0.416, P = 0.03) and McGill (R s =-0.44, P = 0.04). This study is the first to show that OA, not just CPM, correlates with clinical features in fibromyalgia patients and that these two paradigms are inversely correlated and differentially related to disease symptomatology in fibromyalgia.
Conditioned pain modulation (CPM) is assumed to capture endogenous pain modulation. In standard CPM designs, the evaluation of a painful test stimulus (TS) (baseline) is followed by a second evaluation of the TS during/after application of a painful conditioning stimulus (CS) (treatment). However, these standard CPM within designs (baseline always preceding treatment) do not control for order effects, which might help to distinguish specific CPM inhibition from general habituation. To tackle this issue, we conducted 2 separate studies where we controlled for order effects to investigate whether CPM effects depend on the order of baseline and treatment. In both studies, a sample of 60 participants underwent 2 CPM test blocks: one standard order block (baseline before treatment) and one reversed order block (treatment before baseline), separated by a 20-minute break (randomized order across participants). Pain thresholds and pain ratings of phasic heat stimuli served as measures of TS. Cold water (study 1) and cuff pressure algometry (study 2) served as CS. We found significant CPM order effects in both studies and for both measures of TS (pain threshold and ratings). Only the standard CPM order (baseline before treatment) yielded robust pain inhibition effects, whereas the reversed order (treatment before baseline) led to no modulation or seeming pain facilitation. Because control for order effects is otherwise mandatory in within designs, it is surprising that it has been neglected in standard CPM protocols. Finding pain inhibition only in the standard CPM order suggests that CPM inhibition is at least partially confounded with habituation.
