Chronic spinal pain has negative effects on physical and mental well-being. Psychological factors can influence pain tolerance. However, whether these factors influence descending modulatory control mechanisms measured by conditioned pain modulation (CPM) in people with chronic spinal pain is unclear. This systematic review investigated the association between CPM response and psychological factors in people with chronic spinal pain. Published and unpublished literature databases were searched from inception to 23rd October 2023 included MEDLINE, EMBASE, CINAHL, and PubMed. Studies assessing the association between CPM response and psychological factors in people with chronic spinal pain were eligible. Data were pooled through meta-analysis. Methodological quality was assessed using the AXIS tool and the certainty of evidence measured through GRADE. From 2172 records, seven studies (n = 598) were eligible. Quality of included studies was moderate. There was very low certainty of evidence that depression (r = 0.01 [95% CI -0.10 to 0.12], I2 = 0%), and anxiety (r = -0.20 [95% CI -0.56 to 0.16], I2 = 84%), fear avoidance (r = -0.10 [95% CI -0.30 to 0.10], I2 = 70%) had no statistical associations with CPM responder status. Higher pain catastrophising was associated with CPM non-responder status (r = -0.19; 95% CI: -0.37 to -0.02; n = 545; I2: 76%) based on a very low certainty of evidence measured by GRADE. There is currently limited available evidence demonstrating an association between CPM response and psychological factors for people with chronic pain. Managing an individual\'s chronic pain symptoms irrespective of comorbid psychological distress, should continue until evidence offer insights that more targeted interventions are needed.

Central sensitization (CS) involves an amplification of neural processing within the central nervous system that can result in widespread pain patterns and hypersensitivity to stimuli. The Central Sensitization Inventory (CSI) and various quantitative sensory testing (QST) methods purport to assess clinical markers of CS. The purpose of this systematic review and meta-analysis was to summarize and quantify the associations between total CSI scores and QST measures from previous studies. A systematic search identified 39 unique studies that were deemed eligible for the systematic review and 33 studies for meta-analyses (with 3314 subjects and 154 effect sizes), including five QST modalities: conditioned pain modulation, temporal summation, pressure pain threshold, heat pain threshold, and cold pain threshold. The meta-analysis yielded statistically significant CSI-QST correlations in total subject samples for all five QST modalities. The strongest associations were identified between CSI scores and pain threshold testing, especially pressure pain threshold, in which 51% of effects sizes, from 29 studies and 3071 subjects, were determined to be in a medium to large range.

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep-related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP: .31 [95%CI: -.30 to .92]; P = .321; CPM: .40 [95%CI: -.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: -.00 [95%CI: -.22 to .21] P = .970; CPM: .12 [95%CI: -.05 to .29]; P = .181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98-1.88]; P < .001) but not in males (-.30 [95%CI: -2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. PERSPECTIVE: This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). The evidence is very uncertain whether CPM is impaired and TSP facilitated in patients with WAD and NSNP. PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success.

To present the potential use and relevance of the conditioned pain modulation (CPM) response to migraine diagnosis, outcome prediction, and treatment.
The CPM response is a widely used laboratory test to examine inhibitory pain modulation capabilities.
This narrative review summarizes and synthesizes the findings on the CPM response in patients with migraine.
For diagnosis, we summarized the studies comparing CPM responses between patients with migraine and individuals without migraine or with other headache syndromes, as well as between patients with subtypes of migraine. For prediction, we summarized the studies utilizing the CPM response to predict migraine outcome, such as response to interventions. For treatment, we described a device that utilizes the CPM response for acute and preventative migraine treatment. In addition, we suggest the requirements needed for the CPM response to be used for migraine diagnosis, outcome prediction, and treatment.
Although more research is needed, the CPM response could be a useful tool for improving migraine management.

The main aim was to determine the effects of percutaneous electrical nerve stimulation (PENS) and transcutaneous electrical nerve stimulation (TENS) on endogenous pain mechanisms in patients with musculoskeletal pain.
A systematic review and meta-analysis.
The search was conducted on March 1, 2022, in the EMBASE, CINAHL, PubMed, PEDro, Cochrane Library, Web of Science, Medline, and SCOPUS databases. Randomized controlled trials comparing the use of transcutaneous or percutaneous electrostimulation with a placebo, control group, or standard treatment in patients with musculoskeletal pain were included. Outcome measurements were quantitative sensory testing somatosensory variables like pressure pain threshold (PPT), conditioned pain modulation, and temporal summation of pain. The pooled data were evaluated in Review Manager 5.4.
Twenty-four randomized controlled trials (n = 24) were included in the qualitative analysis and 23 in the meta-analysis. The immediate effects of PENS and TENS on local PPTs were significant, with a moderate effect size (standardized mean difference [SMD] 0.53; 95% confidence interval [CI]: 0.34 to 0.72; P < 0.00001). When only studies with a lower risk of bias were analyzed, the heterogeneity decreased from I2 = 58% (P < 0.00001) to I2 = 15% (P = 0.01), and a decrease in the overall effect was observed (SMD 0.33; 95% CI: 0.7 to 0.58). The short-term effects on local PPTs were not significant when compared with the control group (P = 0.13). The mid-term effects on local PPTs were significant, showing a large effect size (SMD 0.55; 95% CI: 0.9 to 1.00; P = 0.02). The immediate effects on conditioned pain modulation were significant, with a large effect size (SMD 0.94; 95% CI: 0.48 to 1.41; P < 0.0001).
PENS and TENS have a mild-moderate immediate effect on local mechanical hyperalgesia in patients with musculoskeletal pain. It appears that these effects are not sustained over time. Analyses suggest an effect on central pain mechanisms producing a moderate increase in remote PPT, an increase in conditioned pain modulation, but further studies are needed to draw clearer conclusions.

The major therapeutic challenge in inflammatory rheumatic diseases is the persistence of pain despite good responses to specific therapies. Central sensitization, which can be assessed clinically by psychophysical measurements, including quantitative sensory testing (QST), is a widely proposed mechanism for chronic pain. In this systematic review, we explored the scientific literature addressing quantitative sensory testing in inflammatory rheumatic diseases. We searched Pubmed and Embase for publications up to December 2021 concerning studies on quantitative sensory testing focusing on pain thresholds, temporal summation (TS) and conditioned pain modulation (CPM), in adult patients with chronic inflammatory rheumatism (e.g. rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, juvenile idiopathic arthritis). The exclusion criteria were reviews, inclusion of children and no reported pain threshold. Data quality was assessed with the National Institutes of Health (NIH) Quality Assessment tools. We identified 27 studies (18 controlled, 9 uncontrolled) including 1875 patients with inflammatory rheumatic diseases and 795 controls. A decrease in pressure pain threshold, in favor of allodynia, was found in 12 of 14 controlled studies on patients with rheumatoid arthritis and spondyloarthritis. The results of other psychophysical tests, including TS and CPM, were inconsistent due to population heterogeneity and a lack of standardization of the patients\' disease duration, activity and treatment. Our review shows that pain in chronic inflammatory rheumatism is associated with pressure allodynia. However, given the heterogeneous quality and discrepant results of studies of other QST outcome measures, the hypothesis of central sensitization involvement in pain processing in these patients cannot be confirmed.

BACKGROUND: Conflicting results exist between somatosensory profiles of patients with temporomandibular myalgia (TMDm). The objective of this review was to examine whether adults with TMDm show altered responses to dynamic quantitative sensory tests compared with healthy controls.
METHODS: We searched five electronic databases for studies, excluding those without suitable controls or where TMDm was associated with confounding non-musculoskeletal disorders. Risk of bias was assessed with the SIGN case-control study checklist. Findings were structured around dynamic quantitative sensory tests and their localization. Where possible, we performed meta-analysis with a random inverse variance model to compare patients with TMDm and healthy controls. Statistical heterogeneity was estimated with Chi² test and inconsistency index, I².
RESULTS: We extracted data from 23 studies comprising 1284 adults with chronic TMDm and 2791 healthy controls. Risk of bias was assessed as high for 20 studies. Mechanical temporal summation, the most studied phenomenon (14 studies), is increased in the upper limb of patients with TMDm (SMD = 0.43; 95% CI: .11 to .75; p = .009) but not in the jaw area (p = .09) or in the cervical area (p = .29). Very little evidence for altered thermal temporal summation (five studies), conditioned pain modulation (seven studies), exercise-induced hypoalgesia (two studies), placebo analgesia (two studies), stress-induced hypoalgesia (one study) and offset analgesia (one study) was found.
CONCLUSIONS: A major limitation of this review was the risk of bias of included studies. Future studies would benefit from following methodological guidelines and consideration of confounding factors.

Conditioned pain modulation (CPM) is a psychophysical parameter that is used to reflect the efficacy of endogenous pain inhibition. CPM reliability is important for research and potential clinical applications. The aim of this systematic review and meta-analysis was to evaluate the reliability of CPM tests in healthy individuals and chronic pain patients.
We searched three databases for peer-reviewed studies published from inception to October 2020: EMBASE, Web of Science and NCBI. Risk of bias and the quality of the included studies were assessed. A meta-analysis with a random effects model was conducted to estimate intraclass correlation coefficients (ICCs).
Meta-analysis was performed on 25 papers that examined healthy participants (k=21) or chronic pain patients (k=4). The highest CPM intra-session reliability was with pressure as test stimulus (TS) and ischemic pressure (IP) or cold pressor test (CPT) as conditioning stimulus (CS) in healthy individuals (ICC 0.64, 95% CI 0.45-0.77), and pressure as TS with CPT as CS in patients (ICC 0.77, 95% CI 0.70-0.82). The highest inter-session ICC was with IP as TS and IP or CPT as CS (ICC 0.51, 95% CI 0.42-0.59) in healthy subjects. The only data available in patients for inter-session reliability were with pressure as TS and CPT as CS (ICC 0.44, 95% CI 0.11-0.69). Quality ranged from very good to excellent using the QACMRR checklist. The majority of the studies (24 out of 25) scored inadequate in Kappa coefficient reporting item of the COSMIN-ROB checklist.
Pressure and CPT were the TS and CS most consistently associated with good to excellent intra-session reliability in healthy volunteers and chronic pain patients. The inter-session reliability was fair or less for all modalities, both in healthy volunteers and chronic pain patients.

OBJECTIVE: Aim of the review is to summarize the knowledge about the sensory function and pain modulatory systems in posttraumatic headache and discuss its possible role in patients with posttraumatic headache.
BACKGROUND: Posttraumatic headache is the most common complication after traumatic brain injury, and significantly impacts patients\' quality of life. Even though it has a high prevalence, its origin and pathophysiology are poorly understood. Thereby, the existing treatment options are insufficient. Identifying its mechanisms can be an important step forward to develop target-based personalized treatment.
METHODS: We searched the PubMed database for studies examining pain modulation and/or quantitative sensory testing in individuals with headache after brain injury.
RESULTS: The studies showed heterogenous alterations in sensory profiles (especially in heat and pressure pain perception) compared to healthy controls and headache-free traumatic brain injury-patients. Furthermore, pain inhibition capacity was found to be diminished in subjects with posttraumatic headache.
CONCLUSIONS: Due to the small number of heterogenous studies a distinct sensory pattern for patients with posttraumatic headache could not be identified. Further research is needed to clarify the underlying mechanisms and biomarkers for prediction of development and persistence of posttraumatic headache.