Impaired Conditioned Pain Modulation Research Articles

Investigating the effects of artificial baroreflex stimulation on pain perception: A comparative study in no-pain and chronic low back pain individuals.

The autonomic nervous system (ANS) and pain exhibit a reciprocal relationship, where acute pain triggers ANS responses, whereas resting ANS activity can influence pain perception. Nociceptive signalling can also be altered by 'top-down' processes occurring in the brain, brainstem and spinal cord, known as 'descending modulation'. By employing the conditioned pain modulation (CPM) paradigm, we previously revealed a connection between reduced low-frequency heart rate variability and CPM. Individuals with chronic pain often experience both ANS dysregulation and impaired CPM. Baroreceptors, which contribute to blood pressure and heart rate variability regulation, may play a significant role in this relationship, although their involvement in pain perception and their functioning in chronic pain have not been sufficiently explored. In the present study, we combined artificial 'baroreceptor stimulation' in both pressure pain and CPM paradigms, seeking to explore the role of baroreceptors in pain perception and descending modulation. In total, 22 individuals with chronic low back pain (CLBP) and 29 individuals with no-pain (NP) took part in the present study. We identified a differential modulation of baroreceptor stimulation on pressure pain between the groups of NP and CLBP participants. Specifically, NP participants perceived less pain in response to baroreflex activation, whereas CLBP participants exhibited increased pain sensitivity. CPM scores were associated with baseline measures of baroreflex sensitivity in both CLBP and NP participants. Our data support the importance of the baroreflex in chronic pain and a possible mechanism of dysregulation involving the interaction between the ANS and descending pain modulation. KEY POINTS: Baroreflex stimulation has different effects on pressure pain in participants with chronic pain compared to matched individuals with no-pain. Baroreceptor activation decreases pain in participants with no-pain but increases pain perception in participants with chronic pain. Baroreflex sensitivity is associated with conditioned pain modulation in both groups of chronic pain and no-pain participants. The reactivity of the baroreflex during autonomic stress demonstrated a positive correlation with Pain Trait scores in participants with chronic back pain.

Psychophysical changes after total sleep deprivation and experimental muscle pain.

Sleep disturbances exacerbate chronic pain, increase psychological load, and increase inflammation. Delayed onset muscle soreness (DOMS) mimics aspects of chronic pain, predominantly affecting peripheral pain mechanisms, while experimental sleep provocations have been shown to impact central pain mechanisms. This study aimed to combine a DOMS model with total sleep deprivation (TSD) to create a novel model affecting both peripheral and central pain mechanisms. A total of 30 healthy participants attended two sessions (baseline and follow-up) separated by 24 h of TSD and a home rating after 48 h. Assessments of interleukin 6 (IL-6) levels, sleep quality, pain catastrophising, affect, and symptoms of depression and anxiety were included in the baseline and follow-up sessions. Additionally, pressure pain and tolerance thresholds, temporal summation, and conditioned pain modulation (CPM) were assessed using cuff-pressure algometry in the baseline and follow-up sessions. DOMS was induced with eccentric calf raises during the baseline session followed by 24 h of TSD. At follow-up pain tolerance (p = 0.012) was significantly reduced, and CPM (p = 0.036) was significantly impaired compared to baseline. Psychological changes included decreases in pain catastrophising (p = 0.027), positive affect (p < 0.001), negative affect (p = 0.003), and anxiety (p = 0.012). Explorative regression models predicted 58% and 68% of DOMS pain intensity after 24 and 48 h, respectively, based on baseline body mass index, pain thresholds, psychological measures, and IL-6 (p < 0.01). Combining DOMS with 1 night of TSD induced pain hypersensitivity, impaired CPM, and altered psychological states. A combination of baseline inflammation, psychological measures, and pain sensitivity significantly predicted DOMS pain intensity after 24 and 48 h.

Sex moderates the association between quantitative sensory testing and acute and chronic pain after total knee/hip arthroplasty.

Acute postsurgical pain (APSP) may persist over time and become chronic. Research on predictors for APSP and chronic postsurgical pain (CPSP) has produced inconsistent results. This observational study aimed to analyze psychological and psychophysical variables associated with APSP and CPSP after total knee or hip arthroplasty, and to explore the role of sex. Assessments were conducted before surgery, 48 h, and 3 months postsurgery, including questionnaires (sociodemographic, pain related, and psychological) and quantitative sensory testing (QST). Hierarchical linear regression models analyzed potential predictors of APSP and CPSP, and moderation analyses evaluated the role of sex. The study included 63 participants undergoing total knee (34, 54%) or hip (29, 46%) arthroplasty. Thirty-one (49.2%) were female and 32 (50.8%) were male. APSP (48 h) was associated with impaired conditioned pain modulation (CPM) (β = 0.301, p = 0.019). CPSP (3 months) was associated with being female (β = 0.282, p = 0.029), longer presurgical pain duration (β = 0.353, p = 0.006), knee arthroplasty (β = -0.312, p = 0.015), higher APSP intensity (β = 373, p = 0.004), and impaired CPM (β = 0.126, p = 0.004). In multivariate analysis, these clinical variables were significant predictors of CPSP, unlike sex, and CPM (adj. R 2 = 0.349). Moderation analyses showed that wind-up ratio (WUR) was a significant predictor of APSP in men (WUR × sex: b = -1.373, p = 0.046) and CPM was a significant predictor of CPSP in women (CPM × sex: b = 1.625, p = 0.016). Specific QST parameters could identify patients at risk for high-intensity APSP and CPSP, with sex as a moderator. This has important clinical implications for patient care, paving the way for developing tailored preventive pain management strategies.

Does the painDETECT questionnaire identify impaired conditioned pain modulation in people with musculoskeletal pain? – a diagnostic accuracy study

BackgroundPeople with neuropathic-like symptoms had more unfavourable pain features than people with nociceptive. Moreover, deficient conditioned pain modulation is common in people with neuropathic-like symptoms. PainDETECT questionnaire have been used to assess the central sensitisation sign and symptoms. However, whether the painDETECT questionnaire can identify the conditioned pain modulation's impairment is still unknown. Therefore, the current study aimed to evaluate the diagnostic accuracy of the painDETECT questionnaire in detecting the impairment of conditioned pain modulation in people with musculoskeletal pain.MethodsWe conducted a diagnostic accuracy comparing the painDETECT questionnaire (index method) with the cold pressor test, the psychophysical test used to assess the conditioned pain modulation (reference standard). We determined diagnostic accuracy by calculating sensitivity, specificity, predictive values, and likely hood ratios.ResultsWe retrospectively enrolled 308 people with musculoskeletal pain in outpatient departments. Most participants were female (n 20 = 220, 71.4%) and had a mean age of 52.2 (± 15.0) years. One hundred seventy-three (56.1%) participants were classified as nociceptive pain, 69 (22.4%) as unclear, and 66 (21.4%) as neuropathic-like symptoms. According to the cold pressor test, 60 (19.4%) participants presented impairment of conditioned pain modulation. The cutoff point of 12 of the painDETECT questionnaire showed values of diagnostic accuracy below 70% compared to the cold pressor test, except for a negative predictive value [76.9 95% Confidence Interval (CI) 71.7 to 81.5]. The cutoff point 19 showed high specificity (78.6%, 95% CI 73.0 to 83.5), high negative predictive value (80.5%, 95% CI 78.1 to 82.7), and accuracy of 67.5% compared to the cold pressor test.ConclusionThe painDETECT questionnaire seems valuable for ruling out people with musculoskeletal pain and impairment of conditioned pain modulation.

Exploration of Somatosensory Function of Patients with Acute Non-specific Neck Pain, Through Quantitative Sensory Testing and Self-reported Symptoms.

Adaptations in somatosensory function characterize several chronic pain conditions, including non-specific neck pain (NNP). Early signs of central sensitization (CS) contribute to pain chronification and poor treatment responses after e.g. whiplash injury and low back pain. Despite this well-established association, the prevalence of CS in patients with acute NNP, and accordingly the potential impact of this association, is still unclear. Therefore, this study aims to investigate whether changes in somatosensory function occur during the acute phase of NNP. This cross-sectional study compared 35 patients with acute NNP, with 27 pain-free individuals. All participants completed standardized questionnaires and an extensive multimodal Quantitative Sensory Testing protocol. A secondary comparison was made with 60 patients with chronic WAD, a population wherein CS is well-established. Compared to pain-free individuals, pressure pain thresholds (PPTs) at remote areas and thermal detection and pain thresholds were unaltered. However, patients with acute NNP showed lower cervical PPTs and conditioned pain modulation, and higher temporal summation, Central Sensitization Index (CSI) scores, and pain intensity. Compared to the group with chronic WAD, PPTs did not differ at any location, yet CSI scores were lower. Changes in somatosensory function occur already in acute NNP. Local mechanical hyperalgesia demonstrated peripheral sensitization, while enhanced pain facilitation, impaired conditioned pain modulation, and self-reported symptoms of CS suggest adaptations in pain processing already early in the stage of NNP.

The association between adverse childhood experiences and peripartal pain experience.

Adverse childhood experiences (ACEs) are associated with altered ongoing and evoked pain experiences, which have scarcely been studied for the peripartum period. We aimed to investigate how ACEs affect pain experience in pregnancy and labor. For this noninterventional trial with a short-term follow-up, pregnant women were divided into a trauma group (TG) with ACEs (n = 84) and a control group (CG) without ACEs (n = 107) according to the Childhood Trauma Questionnaire. Pain experience in pregnancy and labor was recorded by self-report and the German Pain Perception Scale. Pain sensitivity prepartum and postpartum was assessed by Quantitative Sensory Testing and a paradigm of conditioned pain modulation (CPM), using pressure pain thresholds (PPTs) and a cold pressor test. The TG showed higher affective and sensory scores for back pain and a more than doubled prevalence of preexisting back pain. Pelvic pain differences were nonsignificant. The TG also exhibited increased affective scores (1.71 ± 0.15 vs 1.33 ± 0.11), but not sensory scores for labor pain during spontaneous delivery. There were no group differences in prepartum pain sensitivity. While PPTs increased through delivery in the CG (clinical CPM), and this PPT change was positively correlated with the experimental CPM ( r = 0.55), this was not the case in the TG. The association of ACEs with increased peripartal pain affect and heightened risk for preexisting back pain suggest that such women deserve special care. The dissociation of impaired clinical CPM in women with ACEs and normal prepartum experimental CPM implies at least partly different mechanisms of these 2 manifestations of endogenous pain controls.

Impaired conditioned pain modulation was restored after a single exercise session in individuals with and without fibromyalgia.

Exercise is an effective nonpharmacological intervention for individuals with fibromyalgia syndrome (FMS); however, considerable variability is observed in their pain response after a single exercise session that could be due to differences in baseline central pain inhibition (ie, conditioned pain modulation [CPM]). This study examined the effect of isometric exercise on CPM in people with FMS and control participants. A subaim was to identify whether pain inhibition after exercise was due to differences in baseline CPM. Twenty-one individuals with FMS (50.5 ± 14.9 years) and 22 age-matched and sex-matched controls (49.2 ± 13.3 years) participated in a familiarization session and 2 randomized experimental sessions: (1) low-intensity isometric exercise and (2) quiet rest control. Conditioned pain modulation was measured before and after each experimental session. In addition, body composition and physical activity levels were collected to determine potential group differences. Both groups had comparable body composition and physical activity levels and reported similar exercise-induced hypoalgesia (increase in pressure pain thresholds) at the exercising muscle (quadriceps muscle) and systemically (deltoid muscle). Both groups had a decrease in CPM after exercise and quiet rest; however, in both FMS and control participants with impaired baseline CPM, there was an increase in CPM at the deltoid muscle after exercise. In persons with low CPM, irrespective of health status, isometric exercise enhanced CPM at a site distal from the exercising muscle. Our results support the use of isometric exercise when initiating an exercise program especially for individuals with impaired CPM.

A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis

BackgroundThe global burden of osteoarthritis (OA) is steadily increasing due to demographic and lifestyle changes. The nervous system can undergo peripheral and central neuroplastic changes (sensitization) in patients with OA impacting the options to manage the pain adequately. As a result of sensitization, patients with OA show lower pressure pain thresholds (PPTs), facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM). As traditional analgesics (acetaminophen and non-steroidal anti-inflammatory drugs) are not recommended for long-term use in OA, more fundamental knowledge related to other possible management regimes are needed. Duloxetine is a serotonin-noradrenalin reuptake inhibitor, and analgesic effects are documented in patients with OA although the underlying fundamental mechanisms remain unclear. The descending pain inhibitory control system is believed to be dependent on serotonin and noradrenalin. We hypothesized that the analgesic effect of duloxetine could act through these pathways and consequently indirectly reduce pain and sensitization. The aim of this mechanistic study is to investigate if PPTs, TSP, CPM, and clinical pain parameters are modulated by duloxetine.MethodsThis proof of concept study is a randomized, placebo-controlled, double-blinded, crossover trial, which compares PPTs, TSP, and CPM before and after 18 weeks of duloxetine and placebo in forty patients with knee OA. The intervention periods include a titration period (2 weeks), treatment period (60 mg daily for 14 weeks), and a discontinuation period (2 weeks). Intervention periods are separated by 2 weeks.DiscussionDuloxetine is recommended for the treatment of chronic pain, but the underlying mechanisms of the analgesic effects are currently unknown. This study will investigate if duloxetine can modify central pain mechanisms and thereby provide insights into the underlying mechanisms of the analgesic effect.Trial registrationClinicalTrials.govNCT04224584. Registered on January 6, 2020. EudraCT 2019-003437-42. Registered on October 22, 2019. The North Denmark Region Committee on Health Research Ethics N-20190055. Registered on October 31, 2019.

Patients with symptomatic permanent atrial fibrillation show quantitative signs of pain sensitisation

Abstract Background/Introduction Most patients with atrial fibrillation (AF) report symptoms, while around one-third are asymptomatic. We hypothesized that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF. Purpose To assess differences in pain sensitisation in patients with symptomatic and asymptomatic AF. Methods Thirty individuals with permanent AF (15 symptomatic, 15 asymptomatic) completed the AF6 and SF-36 questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalized pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP), and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to quantitative measures of pain sensitisation. Results The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), as well as impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared to the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=−0.50, p=0.005) and sternum (r=−0.42, p=0.02) and positively correlated to TSP of both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=−0.53, p=0.003) but not sternum. Conclusions Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Örebro University, Sweden PPTs tibialis anterior musclePPTs sternum

Bedside clinical tests to assess sensitization in office workers with chronic neck pain

Objective This study aimed to assess pain sensitization in individual office workers with chronic neck pain through simple bedside quantitative sensory tests (QST) and to associate the findings with pain intensity and pain catastrophizing. Methods One hundred-and-four office workers with chronic neck pain were assessed using pressure pain threshold (PPT) considering pain sensitive if PPTs were lower than 155 kPa in the upper trapezius and 245 kPa in the tibialis anterior. Pain sensitive to temporal summation of pain (TSP) was considered if there was a difference of two points in the visual analogue scale (VAS) comparing the first and last stimulus. Pain sensitive was considered to conditioned pain modulation (CPM) if the CPM-effect was less than −7.5%. Pain intensity and catastrophizing were measured using VAS and with the Pain Catastrophizing Scale. Results There was at least one pain sensitive QST finding in 66 office workers (63.5%). TSP findings were the most common (48.1%), followed by PPT’s (31.7%) and CPM (20.2%). Based on the QST findings, office workers were divided based on the number of individual QST findings, and higher pain intensity and pain catastrophizing scores were found in office workers with one (N = 38, P < 0.05) or two (N = 28, P < 0.05) compared with office workers with no QST findings (N = 38). Conclusion This study demonstrated that most office workers with chronic neck pain exhibit either widespread pressure hyperalgesia, facilitated TSP or impaired CPM, indicating pain sensitization within the central nervous system. This was associated with increased clinical pain and pain catastrophizing rumination scores.

Patients with symptomatic permanent atrial fibrillation show quantitative signs of pain sensitisation

ObjectiveMost patients with atrial fibrillation (AF) report symptoms, while one-third are asymptomatic. We hypothesised that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF.MethodsThirty individuals with...

Medial Prefrontal High-Definition Transcranial Direct Current Stimulation to Improve Pain Modulation in Chronic Low Back Pain: A Pilot Randomized Double-blinded Placebo-Controlled Crossover Trial

Chronic low back pain (CLBP) is highly disabling, but often without identifiable source. Focus has been on impaired anti-nociceptive mechanisms contributing to pain maintenance, though methods of targeting this impairment remain limited. This randomised-controlled cross-over pilot trial used active versus sham medial prefrontal cortex (mPFC) high-definition transcranial direct current stimulation (HD-tDCS) for 3-consecutive days to improve descending pain inhibitory function. Twelve CLBP patients were included with an average visual analogue scale (VAS) pain intensity of 3.0 ± 1.5 and pain duration of 5.3 ± 2.6 years. Pressure pain thresholds (PPTs), conditioned pain modulation (CPM), and temporal summation of pain (TSP) assessed by cuff algometry, as well as pain symptomatology (intensity, unpleasantness, quality, disability) and related psychological features (pain catastrophizing, anxiety, affect), were assessed on Day1 before 3 consecutive days of HD-tDCS sessions (each 20 minutes), at 24-hours (Day 4) and 2-weeks (Day 21) following final HD-tDCS. Blinding was successful. No significant differences in psychophysical (PPT, CPM, TSP), symptomatology or psychological outcomes were observed between active and sham HD-tDCS on Day4 and Day21. CPM-effects at Day 1 negatively correlated with change in CPM-effect at Day4 following active HD-tDCS (P = .002). Lack of efficacy was attributed to several factors, not least that patients did not display impaired CPM at baseline. Trial registration: ClinicalTrials.gov (NCT03864822). PerspectiveMedial prefrontal HD-tDCS did not alter pain, psychological nor psychophysical outcomes, though correlational analysis suggested response may depend on baseline pain inhibitory efficacy, with best potential effects in patients with severe impairments in descending pain inhibitory mechanisms. Future work should focus on appropriate patient selection and optimising stimulation targeting.

Do chronic low back pain subgroups derived from dynamic quantitative sensory testing exhibit differing multidimensional profiles?

The relationship of pain sensitivity with pain and disability in low back pain (LBP) is complicated. It has been suggested increased understanding of dynamic quantitative sensory testing (QST) might be useful in increasing understanding of these relationships. This study aimed to create subgroups based on participant responses to dynamic QST, profile these subgroups based on multidimensional variables (including clinical measures of pain and disability, psychological and lifestyle variables and static QST), and investigate the association of subgroup membership with levels of pain intensity, LBP-related disability and disability risk at 12-month follow up. Participants (n=273) with dominant axial chronic non-specific LBP with duration of pain >3months were included in this study. At baseline, eligible participants completed a self-report questionnaire to collect demographic, clinical, psychological and lifestyle data prior to dynamic and static QST. Dynamic QST measures were conditioned pain modulation (CPM) and temporal summation (TS). At 12-months follow up, clinical data were collected, including pain intensity and LBP-related disability. Sub-groups were formed by cross-tabulation. Analysis was undertaken to profile dynamic QST subgroup on demographic, clinical, psychological, lifestyle and static QST measures. Associations between dynamic QST subgroups and follow-up clinical variables were examined. Based on dynamic QST, participants were allocated into four subgroups; normal CPM and normal TS (n=34, 12.5%); normal CPM and facilitated TS (n=6, 2.2%); impaired CPM and normal TS (n=186, 68.1%); impaired CPM and facilitated TS (n=47, 17.2%). At baseline no differences were demonstrated between subgroups across most clinical variables, or any psychological or lifestyle measures. The two subgroups with impaired CPM were more likely to have a higher number of painful body areas. Cold pain sensitivity was heightened in both the subgroups with facilitated TS. Subgroups did not differ across pain intensity, LBP-related disability and disability risk stratification at follow-up. The profiles of people with axial LBP did not vary significantly across dynamic QST subgroups, save forthose in groups with impaired CPM being more likely tohave more widespread symptoms and those with facilitated TS having heightened cold pain sensitivity. Further, subgroup membership was not related to future pain and disability. The role of dynamic QST profiles in LBP remains unclear. Further work is required to understand the role of pain sensitivity in LBP. The utility of dynamic QST subgrouping might not be in determining of future disability. Future research might focus on treatment modifying effects of dynamic QST subgroups.

Effects of multifocal transcranial direct current stimulation targeting the motor network during prolonged experimental pain.

Antinociceptive effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) have been extensively studied in the past years. However, M1 does not work in isolation, but it rather interacts within a network, the so-called resting-state motor network. To explore the anti-nociceptive effects of a new multifocal tDCS approach administered to regions linked to the resting state motor network (network-tDCS) compared to sham tDCS. Healthy individuals were included in this randomized, parallel and double-blinded study comprising two consecutive interventions with 24-hr interval of either active (n=19) or sham (n=19) network-tDCS. Prolonged pain was induced by application of topical capsaicin on the dorsum of the hand during a 24-hr period. Assessments of corticomotor excitability (transcranial magnetic stimulation), pain ratings (numerical rating scale, NRS), skin pain sensitivity on the arm (heat and mechanical), temporal summation of pain (TSP) and conditioned pain modulation (CPM) were performed at baseline (Day1-baseline), after 25min of capsaicin application and before the first tDCS session (Day1-post-cap), and after the second tDCS session (Day2). Comparing Day2 to Day1-baseline measures, there was reduced corticomotor excitability (p<.05) and impaired CPM-effect (p<.05) after sham but not after active network-tDCS. Pain NRS ratings increased at Day2 compared to Day1-post-cap (p<.01) in both groups whereas no significant changes were found in pain sensitivity and TSP. Present findings demonstrate that tDCS applied over regions linked to the resting state motor network reverts the inhibition of corticomotor excitability and CPM impairment both provoked by prolonged experimental pain for 24hr. These findings highlight that the stimulation of the resting state motor network with multifocal tDCS may represent a potential cortical target to treat chronic pain, particularly in patients exhibiting maladaptive corticomotor excitability and impaired conditioned pain modulation effects.

Diagnostic accuracy of the clinical indicators to identify central sensitization pain in patients with musculoskeletal pain

BackgroundThe identification of central sensitization (CS) is an important aspect in the management of patients with chronic musculoskeletal pain. Several methods have been developed, including clinical indicators and psychophysical measures. However, whether clinical indicators coincide with the psychophysical test of CS-related sign and symptoms is still unknown. Therefore, the present study aimed to analyze the diagnostic accuracy of the clinical indicators in identifying CS-related sign and symptoms in patients with musculoskeletal pain.MethodsOne-hundred consecutive patients with musculoskeletal pain were included. Clinical indicators (index method) based on a combination of patient self-report pain characteristics and physical examination were used to identify the phenotype of patients with musculoskeletal pain and the predominance of the CS-related sign and symptoms. Conditioned pain modulation (CPM) was assessed by the Cold Pressor Test (reference standard), which is a psychophysical test used to detect impairment of CPM. Measurements of the diagnostic accuracy were performed.ResultsTwenty-seven patients presented predominance of CS-related sign and symptoms in the assessment of the clinical indicators, and 20 had impairment of CPM. Clinical indicators showed high accuracy (75.0%; 95% confidence interval = 65.3 to 83.1), high specificity (80.0%; 95% confidence interval = 69.6 to 88.1), high negative predictive value (87.7%; 95% confidence interval = 81.2 to 92.1), and a relevant positive likelihood ratio (2.8, 95% confidence interval = 1.5 to 5.0) when compared to the Cold Pressor Test.ConclusionClinical indicators demonstrated a valuable tool for detecting the impaired CPM, which is a remarkable feature of the CS-related sign and symptoms. Clinicians are encouraged to use the clinical indicators in the management of patients with musculoskeletal pain.

The Combination of Preoperative Pain, Conditioned Pain Modulation, and Pain Catastrophizing Predicts Postoperative Pain 12 Months After Total Knee Arthroplasty.

Approximately 20% of knee osteoarthritis patients undergoing total knee arthroplasty (TKA) report chronic postoperative pain. Studies suggest that preoperative variables such as impaired descending pain control, catastrophizing, function, and neuropathic pain-like symptoms may predict postoperative pain 12months after TKA, but the combined prediction value of these factors has not been tested. The current prospective cohort study aimed to combine preoperative risk factors to investigate the predictive value for postoperative pain 12months after TKA. Prospective cohort with follow-up 12months after surgery. A consecutive sample of 131 knee osteoarthritis patients undergoing TKA. Pain intensity, Pain Catastrophizing Scale (PCS) scores, PainDETECT Questionnaire scores, conditioned pain modulation (CPM), and Oxford Knee Score (OKS) were obtained before and 12months after TKA. TKA improved pain (P < 0.001), PCS scores (P < 0.001), PainDETECT Questionnaire scores (P < 0.001), and OKSs (P < 0.001). Preoperative pain correlated with preoperative PCS scores (r = 0.38, P < 0.001), PainDETECT scores (r = 0.53, P < 0.001), and OKSs (r = -0.25, P = 0.001). Preoperative PainDETECT scores were associated with preoperative PCS scores (r = 0.53, P < 0.001) and OKSs (r = -0.25, P = 0.002). Higher postoperative pain was correlated with high preoperative pain (r = 0.424, P < 0.001), PCS scores (r = 0.33, P < 0.001), PainDETECT scores (r = 0.298, P = 0.001), and lower CPM (r = -0.18, P = 0.04). The combination of preoperative pain, PCS score, and CPM explained 20.5% of variance in follow-up pain. PCS scores had a significant effect on pain trajectory when accounting for patient variance (t = 14.41, P < 0.0005). The combination of high preoperative clinical pain intensity, high levels of pain catastrophizing thoughts, and impaired CPM may predict long-term postoperative pain 12months after surgery.

Enhanced amygdala-frontal operculum functional connectivity during rest in women with chronic neck pain: Associations with impaired conditioned pain modulation

BackgroundChronic neck pain is a leading cause of disability worldwide, affecting the lives of millions of people. Research investigating functional brain alterations in relation to somatosensory function is necessary to better understand mechanisms underlying pain development and maintenance in individuals with chronic neck pain, yet remains scarce. This case-control study aimed to examine resting-state functional connectivity alterations and associations with pain outcomes, self-reported central sensitization-related symptoms and quantitative sensory testing (QST) measures in patients with chronic non-traumatic (idiopathic/CINP) neck pain and chronic traumatic (whiplash associated/CWAD) neck pain compared to pain-free controls. MethodsResting-state functional magnetic resonance images were acquired in 107 female participants (38 CINP, 37 CWAD, 32 healthy controls). After data pre-processing, seed-to-seed analyses were conducted focusing on resting-state functional connectivity involving pre-defined regions of interest that have previously been observed to be structurally or functionally altered and/or associated with pain-related measures in this patient population. ResultsFindings demonstrate enhanced left amygdala functional coupling during rest with the left frontal operculum in women with CINP and CWAD compared to controls. This increased resting-state functional connectivity was associated with more self-reported symptoms related to central sensitization and decreased efficacy of conditioned pain modulation. Furthermore, enhanced connectivity between the left amygdala and left frontal orbital cortex, and between the left pallidum and the left frontal operculum was observed only in patients with CWAD compared to healthy controls. In patients, additional associations between local hyperalgesia and enhanced connectivity between the left superior parietal cortex and the left and right precentral gyrus were found. ConclusionsIn line with our hypotheses, patients with CWAD showed the most pronounced alterations in resting-state functional connectivity, encompassing subcortical limbic (amygdala) and basal ganglia (pallidum), and ventral frontal regions (frontal operculum, orbitofrontal cortex) when compared to CINP and controls. Findings are generally in line with the idea of a continuum, in absence of significant group differences across CINP and CWAD. Enhanced amygdala-frontal operculum functional connectivity was the most robust and only connectivity pair in the cluster that was associated with QST (i.e., dynamic QST; endogenous pain inhibition), and that was observed in both patient groups. In addition, independent of group differences, enhanced resting-state functional connectivity between superior parietal cortex (involved in attention) and primary motor cortex was associated with static QST (i.e., greater local hyperalgesia). Taken together, our findings show a key role for enhanced amygdala-ventral frontal circuitry in chronic neck pain, and its association with diminished endogenous pain inhibition further emphasizes the link between cognitive-affective and sensory modulations of pain in women with chronic non-traumatic and traumatic neck pain.

Exploring the Pain in Patellofemoral Pain: A Systematic Review and Meta-Analysis Examining Signs of Central Sensitization.

Patellofemoral pain (PFP) has high recurrence rates and minimal long-term treatment success. Central sensitization refers to dysfunctional pain modulation that occurs when nociceptive neurons become hyperresponsive. Researchers in this area of PFP have been increasingly productive in the past decade. To determine whether evidence supports manifestations of central sensitization in individuals with PFP. We searched MeSH terms for quantitative sensory testing (QST) pressure pain thresholds (PPTs), conditioned pain modulation (CPM), temporal summation, sensitization, hyperalgesia, and anterior knee pain or PFP in PubMed, SPORTDiscus, CINAHL, Academic Search Complete, and EBSCOhost. Peer-reviewed studies that were written in English and published between 2005 and 2020 and investigated QST or pain mapping in a sample with PFP were included in this review. The initial search yielded 140 articles. After duplicates were removed, 78 abstracts were reviewed. The full text of 21 studies was examined, and we included 15 studies in our evaluation: 6 in the meta-analysis, 4 in the systematic review, and 5 in both the meta-analysis and systematic review. A random-effects meta-analysis was conducted for 4 QST variables (local PPTs, remote PPTs, CPM, temporal summation). Strong evidence supported lower local and remote PPTs, impaired CPM, and facilitated temporal summation in individuals with PFP compared with pain-free individuals. Evidence for heat and cold pain thresholds was conflicting. Pain mapping demonstrated expanding pain patterns associated with long duration of PFP symptoms. Signs of central sensitization were present in individuals with PFP, indicating altered pain modulation. The etiologic and treatment models of PFP should reflect the current body of evidence regarding central sensitization. Signs of central sensitization should be monitored clinically, and treatments with central effects should be considered as part of a multimodal plan of care.

Alterations in pronociceptive and antinociceptive mechanisms in patients with low back pain: a systematic review with meta-analysis.

Altered pronociceptive and antinociceptive mechanisms are often implicated in painful conditions and have been increasingly studied over the past decade. For some painful conditions, alterations are well-established, but in populations with low back pain (LBP), there remains considerable debate whether these mechanisms are altered. The present systematic review aimed to address this issue by identifying studies assessing conditioned pain modulation (CPM) and/or temporal summation of pain (TSP) in patients with LBP, comparing with either a healthy control group or using a method with reference data available. Qualitative synthesis and quantitative meta-analysis of group differences were performed. For CPM and TSP, 20 and 29 original articles were eligible, with data for meta-analysis obtainable from 18 (1500 patients and 505 controls) and 27 (1507 patients and 1127 controls) studies, respectively. Most studies were of poor-to-fair quality with significant heterogeneity in study size, population, assessment methodology, and outcome. Nonetheless, CPM was impaired in patients with LBP compared with controls (standardized mean difference = -0.44 [-0.64 to -0.23], P < 0.001), and the magnitude of this impairment was related to pain chronicity (acute/recurrent vs chronic, P = 0.003), duration (RS = -0.62, P = 0.006), and severity (RS = -0.54, P = 0.02). Temporal summation of pain was facilitated in patients with LBP compared with controls (standardized mean difference = 0.50 [0.29-0.72], P < 0.001), and the magnitude of this facilitation was weakly related to pain severity (RS= 0.41, P = 0.04) and appeared to be influenced by test modality (P < 0.001). Impaired CPM and facilitated TSP were present in patients with LBP compared with controls, although the magnitude of differences was small which may direct future research on the clinical utility.

Changes in peripheral and central sensitization in patients undergoing occipital nerve stimulation.

Central sensitization and impaired conditioned pain modulation (CPM) response have been reported to contribute to migraine progression. Migraine patients can present with allodynia possibly attributed to increased sensitivity of peripheral ends of nociceptors with both peripheral and central sensitization. Occipital nerve stimulation (ONS) works by stimulating the distal branches of C1, C2 and C3 possibly altering the nociceptive traffic to the trigemino-cervical complex, brainstem and supranuclear connections. This observational study explores peripheral and central sensitization in patients undergoing percutaneous ONS. Following local regulatory approval, 13 patients undergoing ONS with dual Octrode 90 cm leads and rechargeable implantable pulse generator (IPG) (St Jude) were recruited to have quantitative sensory testing (QST) pre- and post-procedure 2 weeks, 1, 3, 6 and 12 months. Patients with intractable migraine demonstrated impaired CPM (mean baseline pressure pain thresholds (PPTs): 61.98 kPa vs 48.01 kPa cuff inflated) prior to ONS, reverting to an efficient CPM response within 2 weeks following ONS implant (68.9 kPa vs 104.5 kPa cuff inflated) and continuing positively over the next 12 months. In contrast, no statistical difference was observed in PPTs. This is the first reported observation highlighting the effects on central sensitization following ONS. A consistent and sustained improvement in CPM was observed in contrast to PPT's where there was no difference. Normalisation of the CPM response following ONS indicates that the treatment may reduce central sensitization in the migraine population.