Publications by authors named "Lars Arendt-Nielsen"

708 Publications

Strength training in addition to neuromuscular exercise and education in individuals with knee osteoarthritis the effects on pain and sensitization.

Eur J Pain 2021 May 15. Epub 2021 May 15.

The Research Unit PROgrez, Department of Physiotherapy and Occupational Therapy, Naestved-Slagelse-Ringsted Hospitals, Region Zealand, Slagelse, Denmark.

Background: There is a lack of evidence of the relative effects of different exercise modes on pain sensitization and pain intensity in individuals with knee osteoarthritis (KOA).

Methods: Ninety individuals with radiographic and symptomatic KOA, ineligible for knee replacement surgery, were randomized to 12 weeks of twice-weekly strength training in addition to neuromuscular exercise and education (ST+NEMEX-EDU) or neuromuscular exercise and education alone (NEMEX-EDU). Outcomes were bilateral, lower-leg, cuff pressure pain- and tolerance thresholds (PPT, PTT), temporal summation (TS), conditioned pain modulation (CPM), self-reported knee pain intensity, and number of painful body sites.

Results: After 12 weeks of exercise, we found significant differences in increases in PPT (-5.01 kPa (-8.29 to -1.73, p=0.0028)) and PTT (-8.02 kPa (-12.22 to -3.82, p=0.0002)) in the KOA leg in favor of ST+NEMEX-EDU. We found no difference in effects between groups on TS, CPM or number of painful body sites. In contrast, there were significantly greater pain-relieving effects on VAS mean knee pain during the last week (-8.4 mm (-16.2 to -0.5, p=0.0364) and during function (-16.0 mm (-24.8 to -7.3, p=0.0004)) in favor of NEMEX-EDU after 12 weeks of exercise.

Conclusion: Additional strength training reduced pain sensitization compared to neuromuscular exercise and education alone, but also attenuated the reduction in pain intensity compared to neuromuscular exercise and education alone. The study provides the first dose- and type-specific insight into the effects of a sustained exercise period on pain sensitization in KOA. Future studies are needed to elucidate the role of different exercise modes.
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http://dx.doi.org/10.1002/ejp.1796DOI Listing
May 2021

Development of a bedside tool kit for assessing sensitization in patients with chronic osteoarthritis knee pain or chronic knee pain after total knee replacement.

Pain 2021 May 10. Epub 2021 May 10.

Division of Neurological Pain Research and Therapy, Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany Center for Neuroplasticity and Pain & Sport Sciences - Performance and Technology, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark Department of Economics and Business Administration, University of Applied Sciences Stralsund, Stralsund, Germany.

Abstract: Different pathophysiological mechanisms contribute to the pain development in osteoarthritis (OA). Sensitization mechanisms play an important role in the amplification and chronification of pain and may predict the therapeutic outcome. Stratification of patients according to their pain mechanisms could help to target pain therapy. This study aimed at developing an easy-to-use, bedside tool-kit to assess sensitization in patients with chronic painful knee OA or chronic pain after total knee replacement (TKR).In total, 100 patients were examined at the most affected knee and extra-segmentally by use of four standardized quantitative sensory testing parameters reflecting sensitization (mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, pressure pain threshold), a bedside testing battery of equivalent parameters including also temporal summation and conditioned pain modulation, and pain questionnaires. Machine learning techniques were applied to identify an appropriate set of bedside screening tools.Approximately half of the patients showed signs of sensitization (46%). Based on machine learning techniques a composition of tests consisting of three modalities were developed. The most adequate bedside tools to detect sensitization were pressure pain sensitivity (pain intensity at 4 ml pressure using a 10 ml blunted syringe), mechanical pinprick pain sensitivity (pain intensity of a 0.7 mm nylon-filament) over the most affected knee, and extra-segmental pressure pain sensitivity (pain threshold).This pilot study presents a first attempt to develop an easy-to-use bedside test to probe sensitization in patients with chronic OA knee pain or chronic pain after TKR. This tool may be used to optimize individualized, mechanism-based pain therapy.
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http://dx.doi.org/10.1097/j.pain.0000000000002335DOI Listing
May 2021

Anti-nociceptive effects of oxytocin receptor modulation in healthy volunteers-A randomized, double-blinded, placebo-controlled study.

Eur J Pain 2021 Apr 21. Epub 2021 Apr 21.

Center for Sensory-Motor Interaction, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in multi-modal experimental pain in humans.

Methods: Twenty-five male volunteers received carbetocin 100 mcg and placebo (0.9% NaCl) on two different sessions in a randomized, double-blinded, cross-over design. Multi-modal quantitative sensory testing (QST) including a model of capsaicin-induced hyperalgesia and allodynia were performed at baseline and at 10, 60 and 120 min after drug administration. QST data were analysed using mixed linear and logistic regression models. Carbetocin plasma concentrations and oxytocin receptor genotypes were quantified and assessed in an exploratory fashion.

Results: An anti-nociceptive effect of carbetocin was observed on intramuscular electrical temporal summation (estimated difference: 1.26 mA, 95% CI 1.01 to 1.56 mA, p = .04) and single-stimulus electrical pain thresholds (estimated difference: 1.21 mA, 95% CI 1.0 to 1.47 mA, p = .05). Furthermore, the area of capsaicin-induced allodynia was reduced after carbetocin compared to placebo (estimated difference: -6.5 cm , 95% CI -9.8 to -3.2 cm , p < .001).

Conclusions: This study provides evidence of an anti-nociceptive effect of carbetocin on experimental pain in humans.

Significance: This study provides evidence of the anti-nociceptive effect of intravenous administration of the oxytocin agonist carbetocin in healthy male volunteers.
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http://dx.doi.org/10.1002/ejp.1781DOI Listing
April 2021

The role of population-based cohorts in understanding the emergence and progression of musculoskeletal pain.

Pain 2021 Apr 19. Epub 2021 Apr 19.

Curtin School of Allied Health, Curtin University, Perth, Western Australia 6845, Australia Department of Health Science and Technology, Faculty of Medicine, Center for Neuroplasticity and Pain (CNAP), SMI, Aalborg University, Aalborg DK, Denmark. RECOVER Injury Research Centre, NHMRC Centre of Research Excellence in Road Traffic Injury, The University of Queensland, Herston, 4006, Australia Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland Finnish Institute of Occupational Health, Oulu, Finland.

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http://dx.doi.org/10.1097/j.pain.0000000000002316DOI Listing
April 2021

Myalgia as a symptom at hospital admission by SARS-CoV-2 infection is associated to persistent musculoskeletal pain as long-term post-COVID sequelae: a case-control study.

Pain 2021 Apr 8. Epub 2021 Apr 8.

Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos (URJC), Madrid. Spain. Center for Neuroplasticity and Pain (CNAP), SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark Department of Neurology, Hospital Clínico San Carlos. Madrid, Spain Department of Public Health, Universidad Rey Juan Carlos (URJC), Madrid. Spain.

Abstract: This study investigated the association between COVID-related myalgia experienced by patients at hospital admission and the presence of post-COVID symptoms. A case-control study including patients hospitalised due to COVID-19 between February 20 and May 31, 2020 was conducted. Patients reporting myalgia and patients without myalgia at hospital admission were scheduled for a telephone interview 7 months after hospital discharge. Hospitalisation and clinical data were collected from medical records. A list of post-COVID symptoms with attention to musculoskeletal pain was evaluated. Anxiety and depressive symptoms, and sleep quality were likewise assessed. From a total 1,200 hospitalised COVID-19 patients, 369 with and 369 without myalgia at hospital admission were assessed 7.2 months (SD 0.6) after hospital discharge. A greater proportion (P=0.03) of patients with myalgia at hospital admission (20%) showed ≥3 post-COVID symptoms when compared with individuals without myalgia (13%). A higher proportion of patients presenting myalgia (OR1.41, 95%CI 1.04-1.90) exhibited musculoskeletal post-COVID pain when compared to those without myalgia. The prevalence of musculoskeletal post-COVID pain in the total sample was 38%. Fifty percent of individuals with pre-existing musculoskeletal pain experienced a worsening of their symptoms after COVID-19. No differences in fatigue, dyspnoea, anxiety/depressive levels or sleep quality were observed between myalgia and non-myalgia groups. The presence of myalgia at hospital admission was associated with pre-existing history of musculoskeletal pain (OR1.62, 95%CI 1.10-2.40). In conclusion, myalgia at the acute phase was associated with musculoskeletal pain as long-term post-COVID sequelae. Additionally, half of patients with pre-existing pain conditions experienced a persistent exacerbation of their previous syndromes.
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http://dx.doi.org/10.1097/j.pain.0000000000002306DOI Listing
April 2021

Pressure pain thresholds in office workers with chronic neck pain: A systematic review and meta-analysis.

Pain Pract 2021 Apr 7. Epub 2021 Apr 7.

SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

Objectives: The purpose of this study was to (a) compare pressure pain threshold (PPT) values between office workers with chronic neck pain and asymptomatic controls; (b) establish reference PPT values in chronic neck pain; and (c) evaluate associations between PPTs and pain intensity, and disability.

Methods: Seven English/Portuguese databases were searched for relevant literature. Studies investigating adult office workers (age >18 years) with chronic neck pain were included if PPTs were an outcome. The risk of bias was assessed using the Downs and Black checklist. Meta-analysis was conducted if a cluster contained at least two studies reporting the same PPTs.

Results: Ten high quality, two low quality, and one poor quality studies were included. The meta-analysis revealed decreased PPT values in the upper trapezius, extensor carpi ulnaris, and tibialis anterior in office workers with chronic neck pain when compared with healthy workers, without a statistical difference (p > 0.05). The PPT reference value in the upper trapezius was 263 kPa (95% confidence interval [CI] = 236.35 to 289.70), and 365 kPa (95% CI = 316.66 to 415.12) for the tibialis anterior in office workers with chronic neck pain. No correlations were found between the upper trapezius PPT and pain intensity and disability.

Conclusion: This meta-analysis found that all the PPT measurements were not significantly reduced in office workers with chronic neck pain compared with healthy workers. These assumptions were based on a small sample of existing studies, and therefore further studies are necessary to quantify the differences in PPTs. Hypersensitivity PPT reference values are proposed for localized and extrasegmental sites in office workers with chronic neck pain.
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http://dx.doi.org/10.1111/papr.13014DOI Listing
April 2021

Presenting the outputs of the IASP Presidential Task Force on Cannabis and Cannabinoid Analgesia.

Pain 2021 Mar 16. Epub 2021 Mar 16.

Pain Research, Department of Surgery and Cancer, Imperial College, London, United Kingdom Endless Possibilities Initiative, Fraser, CO, United States Center for Neuroplasticity and Pain (CNAP), SMI, School of Medicine, Aalborg University, Aalborg, Denmark.

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http://dx.doi.org/10.1097/j.pain.0000000000002210DOI Listing
March 2021

Is pain associated with premature mortality in patients with psoriatic arthritis? A nested case-control study using the DANBIO Register.

Rheumatology (Oxford) 2021 Mar 1. Epub 2021 Mar 1.

Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark.

Background: It has been hypothesized that the presence of chronic pain causes excess mortality. Since chronic pain is prevalent among patients with psoriatic arthritis this potential association should be explored.

Objectives: To investigate whether higher cumulative pain intensity is associated with an excess mortality risk in patients with psoriatic arthritis.

Methods: A nested case-control study using data from the nationwide DANBIO register and Danish healthcare registers. Cases were patients who died and corresponding to the date of death, matched on sex, year of birth and calendar period at the time of death with up to five controls. Exposure of interest was mean pain intensity reported during the time followed in routine rheumatology practice. Pain intensity was measured using a visual analogue scale from 0 to 100 and conditional logistic regression was used to calculate odds of mortality per 5 unit increase in pain while adjusting for confounders.

Results: The cohort consisted of 8019 patients. 276 cases were identified and matched with 1187 controls. Higher mean pain intensity was associated with increased odds of mortality (OR 1.06, 95%CI 1.02 to 1.10) in the crude model, but there was no association (OR 0.99, 95%CI 0.95 to 1.03) when adjusting for additional confounders. Factors shown to increase the odds of mortality were recent glucocorticoid use, concomitant chronic obstructive pulmonary disease, diabetes mellitus, cancer and cardiovascular disease.

Conclusion: These results indicate that experienced pain in itself is not associated with premature mortality in patients with psoriatic arthritis. However, recent glucocorticoid use and concurrent comorbidities were.
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http://dx.doi.org/10.1093/rheumatology/keab192DOI Listing
March 2021

Sensitization in office workers with chronic neck pain in different pain conditions and intensities.

Scand J Pain 2021 Feb 23. Epub 2021 Feb 23.

SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

Objectives: Office workers with chronic neck pain demonstrates signs of widespread hyperalgesia, less efficient descending pain modulation, which could indicate sensitization of central pain pathways. No studies have assessed a wide variety of office workers with different chronic neck pain disorders and assessed the impact of pain intensity on assessments of central pain pathways. This study aimed to assessed pressure pain thresholds (PPTs), temporal summation of pain (TSP) and conditioned pain modulation (CPM) and to associate these with pain intensity and disability in subgroups of office workers.

Methods: One hundred-and-seventy-one office workers were distributed into groups of asymptomatic and chronic neck pain subjects. Chronic neck pain was categorized as chronic trapezius myalgia and chronic non-specific neck pain and as 'mild-pain' (Visual Analog Scale [VAS]≤3) and 'moderate-pain' (VAS>3) groups. PPTs, TSP, CPM, and Copenhagen Psychosocial Questionnaire II were assessed in all subjects. Neck Disability Index and Pain Catastrophizing Scale were assessed in all the symptomatic office workers.

Results: PPTs were lower in moderate pain (n=49) and chronic trapezius myalgia (n=56) compared with asymptomatic subjects (n=62, p<0.05). TSP was facilitated in moderate pain group compared with mild pain (n=60, p<0.0001) group and asymptomatic subjects (p<0.0001). No differences were found in CPM comparing the different groups (p<0.05). Multiple regression analysis identified Neck Disability Index and TSP as independent factors for prediction of pain intensity in chronic trapezius myalgia (R=0.319) and chronic non-specific neck pain (R=0.208). Somatic stress, stress and sleep as independent factors in chronic non-specific neck pain (R=0.525), and stress in moderate pain group (R=0.494) for the prediction of disability.

Conclusions: Office workers with chronic trapezius myalgia and moderate pain intensity showed significant signs of widespread pressure hyperalgesia. Moreover, the moderate pain group demonstrated facilitated TSP indicating sensitization of central pain pathways. Neck Disability Index and TSP were independent predictors for pain intensity in pain groups. Sleep and stress were independent predictors for disability.
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http://dx.doi.org/10.1515/sjpain-2020-0107DOI Listing
February 2021

Effect of Topical Analgesia on Desensitization Following 8% Topical Capsaicin Application.

J Pain 2021 Jan 30. Epub 2021 Jan 30.

Laboratory for Experimental Cutaneous Pain and Itch Research, SMI, Center for Neuroplasticity and Pain, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark.

To prevent pain associated with 8% capsaicin application, pretreatment with local anesthetics, such as EMLA (eutectic mixture of lidocaine 2.5% and prilocaine 2.5%), is considered an option. However, there is contradicting evidence regarding the effects of local analgesia on capsaicin-induced desensitization. In session 1, 2 skin areas in each forearm of 24 healthy volunteers were randomized to 2-hour pretreatment with EMLA/placebo cream. After pretreatment, 8% capsaicin patches were applied for 3 hours in 1 placebo and 1 EMLA pretreated area, obtaining the following four areas: Capsaicin + EMLA, Capsaicin + Placebo, EMLA alone, and Placebo. Pain intensity scores were assessed during the 3-hour application of capsaicin. Warmth detection, heat pain sensitivity, and microvascular reactivity were measured after the removal of capsaicin. After 24 hours, in session 2, all tests were repeated followed by histamine application in each area to examine itch intensity and neurogenic flare. Overall, EMLA caused significant reductions in capsaicin-induced pain compared with placebo (P= .007) and enhanced the capsaicin-induced increase in superficial blood perfusion immediately after the 3-hour capsaicin application (P< .01). Regardless of pretreatment, capsaicin induced heat hyperalgesia immediately after the application (P< .001). Twenty-four hours post application, heat pain sensitivity was normalized. However, WDT increased significantly (P< .001). Capsaicin tended to reduce the itch intensity and significantly reduced the neurogenic flare (P< .05) induced by histamine compared with EMLA alone. The findings suggest that pretreatment with topical analgesic cream reduces application site pain without interfering with the 8% topical capsaicin-induced desensitization. PERSPECTIVE: Pretreatment with local anesthetic EMLA cream might be considered a good therapeutic option to reduce the pain associated with 8% capsaicin application currently used for treatment of neuropathic pain syndromes. This study also suggests the existence of a synergistic effect of capsaicin and EMLA on the process of neurogenic inflammation.
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http://dx.doi.org/10.1016/j.jpain.2021.01.005DOI Listing
January 2021

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

Pain Med 2021 Jan 7. Epub 2021 Jan 7.

SMI, Faculty of Medicine, Department of Health Science and Technology.

Objectives: 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 12 months 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 12 months after TKA.

Design: Prospective cohort with follow-up 12 months after surgery.

Patients: A consecutive sample of 131 knee osteoarthritis patients undergoing TKA.

Methods: Pain intensity, Pain Catastrophizing Scale (PCS) scores, PainDETECT Questionnaire scores, conditioned pain modulation (CPM), and Oxford Knee Score (OKS) were obtained before and 12 months after TKA.

Results: 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).

Conclusion: The combination of high preoperative clinical pain intensity, high levels of pain catastrophizing thoughts, and impaired CPM may predict long-term postoperative pain 12 months after surgery.
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http://dx.doi.org/10.1093/pm/pnaa402DOI Listing
January 2021

Understanding Pain Catastrophizing: Putting Pieces Together.

Front Psychol 2020 16;11:603420. Epub 2020 Dec 16.

Center for Neuroplasticity and Pain, SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

The present narrative review addresses issues concerning the defining criteria and conceptual underpinnings of pain catastrophizing. To date, the concept of pain catastrophizing has been extensively used in many clinical and experimental contexts and it is considered as one of the most important psychological correlate of pain chronicity and disability. Although its extensive use, we are still facing important problems related to its defining criteria and conceptual understanding. At present, there is no general theoretical agreement of what catastrophizing really is. The lack of a consensus on its definition and conceptual issues has important consequences on the choice of the pain management approaches, defining and identifying problems, and promoting novel research. Clinical and research work in absence of a common theoretical ground is often trivial. It is very surprising that clinical and experimental work has grown extensively in the past years, without a common ground in the form of a clear definition of pain catastrophizing and overview of its conceptual basis. Improving the efficacy and efficiency of pan catastrophizing related treatments requires an understanding of the theoretical construct. So far, most interventions have only demonstrated modest effects in reducing pain catastrophizing. Therefore, clarifying the construct may be an important precursor for developing more targeted and effective interventions, thereby easing some of the burden related to this aspect of pain. In our review, we have extracted and de-constructed common elements that emerge from different theoretical models with the aim to understand the concept of catastrophizing, which components can be modulated by psychological interventions, and the general role in pain processing. The analysis of the literature has indicated essential key elements to explain pain catastrophizing: emotional regulation, catastrophic worry (as repetitive negative thinking), rumination, behavioral inhibition and behavioral activation (BIS/BAS) systems, and interoceptive sensitivity. The present paper attempts to integrate these key elements with the aim to re-compose and unify the concept within a modern biopsychosocial interpretation of catastrophizing.
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http://dx.doi.org/10.3389/fpsyg.2020.603420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772183PMC
December 2020

Patients With High Chronic Postoperative Knee Pain 5 Years After Total Knee Replacement Demonstrate Low-grad Inflammation, Impairment of Function, and High Levels of Pain Catastrophizing.

Clin J Pain 2021 Mar;37(3):161-167

Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology.

Objectives: Total knee replacement (TKR) normally provides improvements of physical function and reduces pain. However, ∼20% of the patients report chronic postoperative knee pain. The aims of the present study were to assess the pain, physical function, and physiological characteristics 5 years after TKR surgery.

Materials And Methods: Eighty patients were recruited 5 years after TKR and divided into 2 groups based on their average 24-hour knee pain intensity assessed on a visual analog scale (VAS 0 to 10) ("high pain group": VAS≥3; "low pain group": VAS<3). The patients completed the PainDETECT Questionnaire (PDQ), Oxford Knee Score (OKS), Pain Catastrophizing Scale, and Forgotten Joint Score-12. Furthermore, the patients underwent a clinical examination of the knees and high-sensitivity serum C-reactive protein was measured as an inflammatory marker.

Results: A total of 53% of the patients in the high pain group were not satisfied with the outcome, while only 11% of the patients in the low pain group was not satisfied, and the pain intensities in the 2 groups were 5.1 (4.6 to 5 to 6) and 1.1 (0.6 to 1.5) (P<0.001), respectively. Furthermore, the high pain group demonstrates worse scores in: Forgotten Joint Score-12 (P=0.001), OKS function (P<0.001), OKS pain (P<0.001), and Pain Catastrophizing Scale (P<0.001).The high pain group demonstrated increased level of high-sensitivity serum C-reactive protein (4.3 mg/L [3.2 to 5.5] vs. 1.7 mg/L [1.2 to 2.2], P<0.001), and decreased range of motion in the knee (110 vs. 119-degree range of motion, P=0.013).

Discussion: Patients with high chronic postoperative knee pain 5 years after TKR demonstrate decreased physical function, higher levels of catastrophizing thoughts, and increased levels of inflammation.
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http://dx.doi.org/10.1097/AJP.0000000000000907DOI Listing
March 2021

Time course of DNA methylation in pain conditions: From experimental models to humans.

Eur J Pain 2021 02 10;25(2):296-312. Epub 2020 Nov 10.

Center for Neuroplasticity and Pain (CNAP), SMI®, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

Background And Objective: Throughout the last decade, research has uncovered associations between pain and epigenetic alterations caused by environmental factors. Specifically, studies have demonstrated correlations between pain conditions and altered DNA methylation patterns. Thus, DNA methylation has been revealed as a possible modulator or contributor to pain conditions, providing a potential therapeutic target for treatment by DNA methylation modification. To develop such treatments, it is necessary to clarify a wide number of aspects on how DNA methylation affects pain perception; first and foremost, the temporal dynamics. The objective of the present review is to provide an overview of current knowledge on temporal dynamics of DNA methylation in response to pain, and to investigate if a timeframe can be established based on the data of currently published studies.

Databases And Data Treatment: PubMed, MEDLINE, Google Scholar and Embase were searched comprehensively for studies of DNA methylation in neuropathic, inflammatory and alternative animal pain models, and in chronic pain patients including Complex Regional Pain Syndrome, chronic postsurgical pain, chronic widespread pain, fibromyalgia and Crohn's disease.

Results: We identified 34 articles highlighting variations in temporal dynamics of DNA methylation across species and between different types of pain. These studies represent a starting point to uncover new insights in the DNA methylation time course in pain.

Conclusions: No timeframe can currently be made for the DNA methylation response to pain in any of the reviewed conditions, highlighting an important focus area for future research.
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http://dx.doi.org/10.1002/ejp.1674DOI Listing
February 2021

Cold pain hypersensitivity predicts trajectories of pain and disability after low back surgery: a prospective cohort study.

Pain 2021 01;162(1):184-194

Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States.

Improving the ability to predict persistent pain after spine surgery would allow identification of patients at risk and guide treatment decisions. Quantitative sensory tests (QST) are measures of altered pain processes, but in our previous study, preoperative QST did not predict pain and disability at single time-points. Trajectory analysis accounts for time-dependent patterns. We hypothesized that QST predict trajectories of pain and disability during 1 year after low back surgery. We performed a trajectory analysis on the cohort of our previous study (n = 141). Baseline QST included electrical, pressure, heat, and cold stimulation of the low back and lower extremity, temporal summation, and conditioned pain modulation. Pain intensity and Oswestry Disability Index were measured before, and 2, 6, and 12 months after surgery. Bivariate trajectories for pain and disability were computed using group-based trajectory models. Multivariable regressions were used to identify QST as predictors of trajectory groups, with sociodemographic, psychological, and clinical characteristics as covariates. Cold pain hypersensitivity at the leg, not being married, and long pain duration independently predicted worse recovery (complete-to-incomplete, incomplete-to-no recovery). Cold pain hypersensitivity increased the odds for worse recovery by 3.8 (95% confidence intervals 1.8-8.0, P < 0.001) and 3.0 (1.3-7.0, P = 0.012) in the univariable and multivariable analyses, respectively. Trajectory analysis, but not analysis at single time-points, identified cold pain hypersensitivity as strong predictor of worse recovery, supporting altered pain processes as predisposing factor for persisting pain and disability, and a broader use of trajectory analysis. Assessment of cold pain sensitivity may be a clinically applicable, prognostic test.
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http://dx.doi.org/10.1097/j.pain.0000000000002006DOI Listing
January 2021

Preoperative serum circulating microRNAs as potential biomarkers for chronic postoperative pain after total knee replacement.

Mol Pain 2020 Jan-Dec;16:1744806920962925

Center for Sensory-Motor Interaction, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

Background: Chronic postoperative pain affects approximately 20% of patients with knee osteoarthritis after total knee replacement. Circulating microRNAs can be found in serum and might act as biomarkers in a variety of diseases. The current study aimed to investigate the preoperative expression of circulating microRNAs as potential predictive biomarkers for the development of chronic postoperative pain in the year following total knee replacement.

Methods: Serum samples, collected preoperatively from 136 knee osteoarthritis patients, were analyzed for 21 circulatory microRNAs. Pain intensity was assessed using a visual analog scale before and one year after total knee replacement. Patients were divided into a low-pain relief group (pain relief percentage <30%) and a high-pain relief group (pain relief percentage >30%) based on their pain relief one year after total knee replacement, and differences in microRNAs expression were analyzed between the two groups.

Results: We found that three microRNAs were preoperatively dysregulated in serum in the low-pain relief group compared with the high-pain relief group. MicroRNAs hsa-miR-146a-5p, -145-5p, and -130 b-3p exhibited fold changes of 1.50, 1.55, and 1.61, respectively, between the groups (all P values < 0.05). Hsa-miR-146a-5p and preoperative pain intensity correlated positively with postoperative pain relief (respectively, R = 0.300, P = 0.006; R = 0.500, P < 0.001).

Discussion: This study showed that patients with a low postoperative pain relief present a dysregulation of circulating microRNAs. Altered circulatory microRNAs expression correlated with postoperative pain relief, indicating that microRNAs can serve as predictive biomarkers of pain outcome after surgery and hence may foster new strategies for preventing chronic postoperative pain after total knee replacement (TKR).
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http://dx.doi.org/10.1177/1744806920962925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543153PMC
October 2020

Pain, sensitization and physical performances in patients with chronic painful knee osteoarthritis or chronic pain following total knee arthroplasty: An explorative study.

Eur J Pain 2021 01 7;25(1):213-224. Epub 2020 Oct 7.

Sports Sciences - Performance and Technology, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg East, Denmark.

Background: The aim of this study was to assess clinical pain, pain sensitization and physical performances to profile patients with chronic painful knee osteoarthritis (OA) or pain after total knee arthroplasty (TKA). Examining the interactions between pain mechanisms and physical performances would enable us to investigate the underlying explanatory relationships between these parameters.

Methods: In this explorative study, 70 patients with chronic painful knee OA (N = 46) or chronic pain after TKA (N = 24) were assessed for clinical pain, quantitative sensory profiling (mechanical pinprick pain sensitivity, temporal summation (TS) and conditioned pain modulation), physical performances (chair stand, walk and stair climb tests) and self-reported outcomes. Between-group comparisons were made using ANCOVA tests and associations between outcomes were analysed using multivariate linear regression models.

Results: Overall, no differences between groups regarding clinical pain and quantitative sensory profiling outcomes were observed. Physical performances were lower in the TKA group compared with the OA group with moderate-to-large effect sizes, and a tendency towards better scores in self-reported outcomes for the OA group was observed with small-to-moderate effect sizes. Self-reported function seems to be associated with physical performances in the TKA group. Sensitization (TS) appears to be associated with poorer physical performances in the OA group.

Conclusions: Similar profiles for pain intensity, signs of sensitization and conditioned pain modulation were observed. Patients with TKA seems to have impaired physical performances compared with the OA group, underlining the importance of targeting physical performances. Only the OA patients showed an association between sensitization (TS) and physical performance.

Significance: Quantitative pain profiling assessment was used to assess pain intensities and pain mechanisms. We observed associations between physical performances and temporal summation in the OA group underlining the importance of assessing motor functions and pain mechanisms in the same trial. We observed lower levels of physical performances in the TKA group compared with the OA group, suggesting that examination and rehabilitation of physical performances is essential for TKA patients with chronic pain.
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http://dx.doi.org/10.1002/ejp.1663DOI Listing
January 2021

Exosomes as a new pain biomarker opportunity.

Mol Pain 2020 Jan-Dec;16:1744806920957800

Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.

Exosomes are extracellular microvesicles implicated in intercellular communication with ability to transfer cargo molecules, including protein, lipids, and nucleic acids, at both close and distant target sites. It has been shown that exosomes are implicated in physiological and pathological processes. In recent years, the interest on exosomes' role in many pain states has increased. Their involvements in pain processes have been demonstrated by studies on different chronic pain diseases, both inflammatory and neuropathic, such as osteoarthritis, rheumatoid arthritis, inflammatory bowel diseases, neurodegenerative pathologies, complex regional pain syndrome, and peripheral nerve injury. Animal and clinical studies investigated exosomes-based treatments, showing their ability to improve painful symptoms with fewer side effects, with potential immunoprotective and anti-inflammatory effect. Specific molecular patterns characterize exosomes' cargo according to the cellular origin, epigenetic modifications, environmental state, and stressor factors. Therefore, the identification of specific cargo's profile associated to pain states may lead to recognize specific pathological states and to consider the use of exosomes as biomarkers of diseases. Furthermore, exosomes' ability to transfer information and their presence in many accessible biological fluids suggest a potential use as novel non-invasive therapeutic tools in pain field.
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http://dx.doi.org/10.1177/1744806920957800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493250PMC
September 2020

Preoperative quantitative sensory testing and robot-assisted laparoscopic hysterectomy for endometrial cancer: can chronic postoperative pain be predicted?

Scand J Pain 2020 10;20(4):693-705

Center for Sensory-Motor Interaction, Center for Neuroplasticity and Pain, Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, Aalborg, Denmark.

Objectives Chronic postoperative pain is prevalent after robot-assisted laparoscopic hysterectomy for endometrial cancer. Preoperative Quantitative Sensory Testing (QST) has been utilized to identify patients at risk of developing chronic postoperative pain after a range of surgical procedures. The aim of this prospective, observational study was to (1) determine the prevalence of chronic postoperative pain, (2) assess selected preoperative risk factors for chronic postoperative pain, and (3) evaluate if preoperative QST profiling could predict the development of chronic postoperative pain following robot-assisted laparoscopic hysterectomy for endometrial cancer. Methods One-hundred and sixty consecutive patients were included and handheld pressure algometry, cuff pressure algometry, temporal summation of pain, conditioned pain modulation, and heat pain thresholds were assessed prior to surgery. Patients were asked to fill out a questionnaire concerning pain in the pre- and post-operative time period six months after surgery. Chronic postoperative pain was defined as persistent, moderate to severe pain (mean visual analogue scale (VAS)≥3) on a daily basis six months after surgery. Results The prevalence of chronic postoperative pain after robot-assisted laparoscopic hysterectomy for endometrial cancer was of 13.6% (95% CI 8.4-20.4%). Patients that would develop chronic postoperative pain had a lower BMI (p=0.032), a higher prevalence of preoperative pelvic pain (p<0.001), preoperative heat pain hyperalgesia (p=0.043) and a higher level of acute postoperative pain (p<0.001) when compared to patients that would not develop chronic postoperative pain. A logistic regression model demonstrated that the presence of preoperative pelvic pain was a significant, independent predictive risk factor for development of chronic postoperative pain (OR=6.62, 95% CI 2.26-19.44), whereas none of the QST parameters could predict postoperative pain. Conclusions Preoperative QST assessment could not predict the development of chronic postoperative pain despite preoperative heat pain hyperalgesia in patients that would develop chronic postoperative pain.
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http://dx.doi.org/10.1515/sjpain-2020-0030DOI Listing
October 2020

[Opioids for chronic non-malignant pain].

Ugeskr Laeger 2020 Jul;182(28)

In recent years, the use of opioids in Denmark has been under scrutiny due to various government measures to reduce consumption, greater media focus and Denmark's relatively larger consumption of opioids compared with the Nordic neighbours. Consequently, opioid prescriptions in Denmark have declined since 2017. A more nuanced approach to opioid treatment for non-malignant chronic pain, which includes individualised treatment as well as enhanced interdisciplinary collaboration, is required as argued in this review.
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July 2020

Association of dynamic and widespread mechanical sensitivity in cluster headache.

Acta Neurol Belg 2020 Oct 24;120(5):1265-1270. Epub 2020 Jul 24.

Neurology Department, Hospital Clínico San Carlos, Madrid, Spain.

We investigated if dynamic pressure pain sensitivity in the symptomatic area is associated with pressure sensitivity in local and distant pain-free areas in cluster headache (CH). A pressure algometry set consisting of 8 rollers with fixed pressure levels ranging from 500 to 5300 g was used to assess dynamic pressure pain sensitivity in men with episodic CH. Each roller was moved from an anterior-to-posterior direction over the temporalis muscle. The load level of the first painful roller was considered the dynamic pain threshold (DPT). Further, pain elicited during DPT (roller evoked pain) was also assessed. We used a pressure algometer to determine pressure pain thresholds (PPTs) over the temporalis muscle, C5/C6 joint, second metacarpal, and tibialis anterior. Patients were assessed in an asymptomatic (remission) phase, at least 6 months after their last cluster period and without taking pharmacological treatment. Forty men with episodic CH (mean age 42 years) were included. Both outcomes, DPTs (r = 0.781, P < 0.001) and roller-evoked pain (r = 0.586; P < 0.001) were bilaterally correlated. Further, DPT, but not roller-evoked pain, was moderately associated with PPTs measured at the symptomatic (temporalis: r = 0.665, P < 0.001) and distant pain-free (C5-C6 joint: r = 0.389, P = 0.013; second metacarpal: r = 0.551, P < 0.001; and, tibialis anterior: r = 0.308, P = 0.035) points. Dynamic pressure sensitivity in the trigeminal area was correlated to pressure pain sensitivity at both symptomatic and distant pain-free areas in men with CH supporting the use of roller pressure algometry. Dynamic pressure algometry may be a new tool for assessing the status of sensitization in primary headaches.
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http://dx.doi.org/10.1007/s13760-020-01450-yDOI Listing
October 2020

The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain.

Pain 2021 01;162(1):31-44

SMI, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability. A systematic search of MEDLINE and EMBASE yielded 25 studies on surgical interventions and 11 on pharmacological interventions. Seventeen surgical and 11 pharmacological studies reported an association between preoperative or pretreatment QST and chronic postoperative pain or analgesic effect. The most commonly assessed QST modalities were pressure stimuli (17 studies), temporal summation of pain (TSP, 14 studies), and conditioned pain modulation (CPM, 16 studies). Of those, the dynamic QST parameters TSP (50%) and CPM (44%) were most frequently associated with chronic postoperative pain and analgesic effects. A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found. Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses. This systematic review demonstrates that TSP and CPM show the most consistent predictive values for chronic postoperative pain and analgesic effect, but the heterogeneous methodologies reduce the generalizability and hence call for methodological guidelines.
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http://dx.doi.org/10.1097/j.pain.0000000000002019DOI Listing
January 2021

Pain Catastrophizing, Self-reported Disability, and Temporal Summation of Pain Predict Self-reported Pain in Low Back Pain Patients 12 Weeks After General Practitioner Consultation: A Prospective Cohort Study.

Clin J Pain 2020 10;36(10):757-763

SMI, Department of Health Science and Technology, School of Medicine.

Objectives: Patients with low back pain (LBP) often demonstrate pain sensitization, high degree of pain catastrophizing, and psychological distress. This study investigated whether pain sensitization mechanisms, the Pain Catastrophizing Scale (PCS), and Start Back Screening Tool were associated with pain in recurrent LBP patients 12 weeks after consulting their general practitioner (GP).

Materials And Methods: In 45 LBP patients, pressure pain thresholds, temporal summation of pain (TSP), conditioned pain modulation (CPM), the Roland Morris Disability Questionnaire (RMDQ), and the PCS were assessed before consultation. Patients were classified into low to medium or high risk of poor prognosis on the basis of the Start Back Screening Tool. Worst pain within the last 24 hours was assessed on a visual analogue scale (VAS) at inclusion and 12 weeks after GP consultation.

Results: VAS scores were reduced after 12 weeks in the low-to-medium (N=30, P<0.05), but not the high-risk group (N=15, P=0.40). RMDQ was reduced after 12 weeks (P<0.001), but with no difference between the groups. PCS was reduced in the low-to-medium and the high-risk group (P<0.05). TSP was significantly higher at follow-up in the high-risk group compared with the low-to-medium-risk group (P<0.05). A linear regression model explained 54.9% of the variance in VAS scores at follow-up utilizing baseline assessments of TSP, RMDQ, and PCS.

Discussion: This study indicate that patients with LBP and high self-reported disability, high pain catastrophizing, and facilitated TSP assessed when consulting the GP might predictive poor pain progression 12 weeks after the consultation.
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http://dx.doi.org/10.1097/AJP.0000000000000865DOI Listing
October 2020

Four decades later: what's new, what's not in our understanding of pain.

Pain 2020 09;161(9):1943-1944

Department of Health Science and Technology, Center for Pain and Neuroplasticy, School of Medicine, Aalborg University, Aalborg, Denmark.

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http://dx.doi.org/10.1097/j.pain.0000000000001991DOI Listing
September 2020

A novel clinical applicable bed-side tool for assessing conditioning pain modulation: proof-of-concept.

Scand J Pain 2020 10;20(4):801-807

Sports Sciences - Performance and Technology, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg East, Denmark.

Background and aims In recent years, focus on assessing descending pain modulation or conditioning pain modulation (CPM) has emerged in patients with chronic pain. This requires reliable and simple to use bed-side tools to be applied in the clinic. The aim of the present pilot study was to develop and provide proof-of-concept of a simple clinically applicable bed-side tool for assessing CPM. Methods A group of 26 healthy volunteers participated in the experiment. Pressure pain thresholds (PPT) were assessed as test stimuli from the lower leg before, during and 5 min after delivering the conditioning tonic painful pressure stimulation. The tonic stimulus was delivered for 2 min by a custom-made spring-loaded finger pressure device applying a fixed pressure (2.2 kg) to the index finger nail. The pain intensity provoked by the tonic stimulus was continuously recorded on a 0-10 cm Visual Analog Scale (VAS). Results The median tonic pain stimulus intensity was 6.7 cm (interquartile range: 4.6-8.4 cm) on the 10 cm VAS. The mean PPT increased significantly (P = 0.034) by 55 ± 126 kPa from 518 ± 173 kPa before to 573 ± 228 kPa during conditioning stimulation. When analyzing the individual CPM responses (increases in PPT), a distribution of positive and negative CPM responders was observed with 69% of the individuals classified as positive CPM responders (increased PPTs = anti-nociceptive) and the rest as negative CPM responders (no or decreased PPTs = Pro-nociceptive). This particular responder distribution explains the large variation in the averaged CPM responses observed in many CPM studies. The strongest positive CPM response was an increase of 418 kPa and the strongest negative CPM response was a decrease of 140 kPa. Conclusions The present newly developed conditioning pain stimulator provides a simple, applicable tool for routine CPM assessment in clinical practice. Further, reporting averaged CPM effects should be replaced by categorizing volunteers/patients into anti-nociceptive and pro-nociceptive CPM groups. Implications The finger pressure device provided moderate-to-high pain intensities and was useful for inducing conditioning stimuli. Therefore, the finger pressure device could be a useful bed-side method for measuring CPM in clinical settings with limited time available. Future bed-side studies involving patient populations are warranted to determine the usefulness of the method.
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http://dx.doi.org/10.1515/sjpain-2020-0033DOI Listing
October 2020

Nerve Growth Factor Signaling and Its Contribution to Pain.

J Pain Res 2020 26;13:1223-1241. Epub 2020 May 26.

Pfizer, Inc, New York, NY, USA.

Nerve growth factor (NGF) is a neurotrophic protein essential for the growth, differentiation, and survival of sympathetic and sensory afferent neurons during development. A substantial body of evidence, based on both animal and human studies, demonstrates that NGF plays a pivotal role in modulation of nociception in adulthood. This has spurred development of a variety of novel analgesics that target the NGF signaling pathway. Here, we present a narrative review designed to summarize how NGF receptor activation and downstream signaling alters nociception through direct sensitization of nociceptors at the site of injury and changes in gene expression in the dorsal root ganglion that collectively increase nociceptive signaling from the periphery to the central nervous system. This review illustrates that NGF has a well-known and multifunctional role in nociceptive processing, although the precise signaling pathways downstream of NGF receptor activation that mediate nociception are complex and not completely understood. Additionally, much of the existing knowledge derives from studies performed in animal models and may not accurately represent the human condition. However, available data establish a role for NGF in the modulation of nociception through effects on the release of inflammatory mediators, nociceptive ion channel/receptor activity, nociceptive gene expression, and local neuronal sprouting. The role of NGF in nociception and the generation and/or maintenance of chronic pain has led to it becoming a novel and attractive target of pain therapeutics for the treatment of chronic pain conditions.
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http://dx.doi.org/10.2147/JPR.S247472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266393PMC
May 2020

Pain catastrophizing is associated with pain thresholds for heat, cold and pressure in women with chronic pelvic pain.

Scand J Pain 2020 07;20(3):635-646

Department of Obstetrics and Gynaecology in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

Background and aims Psychological traits such as pain catastrophizing may play a role in the development of chronic pelvic pain (CPP). Pain catastrophizing is the tendency to amplify negative cognitive and emotional pain processes. The Pain Catastrophizing Scale (PCS) assesses elements of pain catastrophizing divided into three subgroups of factors (rumination, helplessness and magnification). Previous studies have shown associations between CPP and increased pain sensitivity, widespread generalized hyperalgesia, and decreased pain thresholds, but the relation between pain catastrophizing and specific pain thresholds has not yet been widely examined in this patient group. The aims of this study were (a) to determine if catastrophizing is increased in women with CPP compared with pain-free women, (b) to assess the importance of pain catastrophizing, psychological distress variables, and subjective pain sensitivity for pain thresholds of heat, cold and pressure in these two groups, and (c) to determine whether psychological variables or pain thresholds best contribute to the differentiation between CPP and controls. Methods Thirty-seven women with chronic pelvic pain who underwent diagnostic laparoscopy on the suspicion of endometriosis participated along with 55 healthy and pain-free controls. All underwent quantitative sensory testing on six locations on the body to determine heat (HPT), cold (CPT) and pressure (PPT) pain thresholds. The PCS, the Pain Sensitivity Questionnaire (PSQ), the Hospital Anxiety Depression Scale, (HADS) demographics and clinical data were collected prospectively. Principal component analysis and orthogonal partial least square regressions were used to assess the associations between PCS scores and pain thresholds. Results The women with CPP scored significantly higher on PCS than the healthy controls. PCS-helplessness, PCS-rumination and HADS-depression were significantly associated with pain thresholds for the whole group. In the CPP group, PCS-rumination, body mass index and PSQ were significant regressors for HPT and CPT. The PCS and the HADS subscales were strongly intercorrelated in women with CPP and were stronger regressors of group membership than the three pain thresholds. In the group of healthy control women, no relationships were found to be significant. The psychological variables were somewhat stronger significant regressors than pain thresholds (also significant) for group membership. Conclusions Women with CPP have significantly higher pain catastrophizing scores than women without CPP. The pain catastrophizing rumination factor is significantly associated with pain thresholds of heat and cold in CPP women. PCS and HADS are strongly intercorrelated and PSQ correlates positively with these variables. It seems that the psychological variables are important for group differentiation. Implications The results clearly indicate the need for a multimodal assessment (bio-psycho-social) of CPP patients including psychological symptoms such as catastrophizing, anxiety and depression. The registration of semi-objective pain thresholds captures both specific pain sensitivity information (mechanical pressure, cold or heat) and the degree of wide spread pain hypersensitivity. There is a need for future larger studies investigating whether certain profiles in the clinical presentations (including pain thresholds and psychological variables) are associated with outcomes after different types of interventions.
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http://dx.doi.org/10.1515/sjpain-2020-0015DOI Listing
July 2020

Chronic Postoperative Pain After Hysterectomy for Endometrial Cancer: A Metabolic Profiling Study.

Mol Pain 2020 Jan-Dec;16:1744806920923885

Department of Obstetrics and Gynecology, Aalborg University Hospital, Aalborg, Denmark.

Introduction: One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low-molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain.

Materials And Methods: The study was designed as a nested case-control study within a cohort of women treated for endometrial cancer with robot-assisted laparoscopic hysterectomy. Twenty-six women with chronic postoperative pain were matched on age and body mass index with fifty-two controls without chronic postoperative pain, and metabolic profiling of preoperatively drawn blood samples from a biobank was performed by means of nuclear magnetic resonance spectroscopy.

Results: Nineteen metabolites, including cholesterol, cholesteryl ester, linoleic acid, phospholipids, lipids, and triglycerides had statistically significant higher concentrations in a subgroup of patients who would develop chronic postoperative pain on a later stage compared to the group of patients who would not develop chronic postoperative pain (<0.05). A sparse Partial Least Squares-Discriminant Analysis model explained 38.1% of the variance and had a accuracy of 73.1%.

Conclusions: This study substantiates the hypothesis that certain lipids, lipoproteins, and fatty acids are associated with chronic postoperative pain.
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http://dx.doi.org/10.1177/1744806920923885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227146PMC
May 2020

Discrimination of knee osteoarthritis patients from asymptomatic individuals based on pain sensitivity and knee vibroarthrographic recordings.

Physiol Meas 2020 06 8;41(5):055002. Epub 2020 Jun 8.

Sport Sciences - Performance and Technology, Department of Health Science and Technology, School of Medicine, Aalborg University, Aalborg, Denmark.

Objective: Recording of knee vibroarthrographic (VAG) activity during activities of daily living (ADL) can contribute to diagnose knee osteoarthritis (KOA). However, classifying KOA patients based on knee VAG during ADL has been an elusive problem not related to knee pain. Therefore, the aims of this study was to classify KOA patients based on (1) VAG during ADL and (2) knee pain sensitivity and then compare their results.

Approach: The experimental procedure consisted of the recording of VAG signals during four ADLs (over-ground gait, stairs descent, stairs ascent and sit-to-stand) from eight patellar and peri-patellar locations in 20 KOA and 20 asymptomatic participants. Pressure pain thresholds (PPT) were obtained from eight locations around the knee joint to quantify pain sensitivity. A random forest classifier was utilized to identify KOA patients based on VAG signal features and PPTs. The most important features contributing to the classification accuracy were determined. The KOA patients participated in a second identical experimental session to examine the day-to-day reproducibility.

Main Results: The participants were classified with accuracy of 90%, 70%, 64% and 82% during over-ground gait, stairs descent, stairs ascent and sit to stand, respectively. However, the accuracy of the classifier was reduced by about 10%-25% due to a systematic bias in the extracted features across days. Features of the VAG signals in time and frequency domains as well as nonlinear features were found importantly contributing towards the classification accuracy. The VAG features extracted from the lateral side of the knee was found to be more informative than other locations. The classification based on PPT reached 77%. Medial and proximal knee PPT points contributed to the classification accuracy.

Significance: This study showed that using multichannel VAG signals to identify KOA patients allows better accuracy than the use of PPTs. However, VAG setup must be standardized to avoid day-to-day bias.
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http://dx.doi.org/10.1088/1361-6579/ab8857DOI Listing
June 2020

Dynamic Pressure Pain Hypersensitivity as Assessed by Roller Pressure Algometry in Episodic Cluster Headache.

Pain Physician 2020 03;23(2):219-227

Headache Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.

Background: A method for assessing dynamic muscle hyperalgesia (dynamic pressure algometry) has been developed and applied in tension-type and migraine headaches.

Objectives: To investigate differences in dynamic pressure pain assessment over the trigeminal area between men with cluster headache (CH) and headache-free controls, and the association between dynamic and static pressure pain sensitivity.

Study Design: A case-control study.

Setting: Tertiary urban hospital.

Methods: Forty men with episodic CH and 40 matched controls participated. Dynamic pressure pain sensitivity was assessed with a dynamic pressure algometry set consisting of 8 rollers with different fixed levels (500, 700, 850, 1,350, 1,550, 2,200, 3,850, and 5,300 g). Each roller was moved at a speed of 0.5 cm/sec over a diagonal line covering the temporalis muscle from an anterior to posterior direction. The dynamic pressure threshold (DPT; load level of the first painful roller) and the pain intensity perceived at the DPT level (roller-evoked pain) were assessed. Static pressure pain thresholds (PPT) were also assessed with a digital pressure algometer applied statically over the mid-muscle belly of the temporalis. Patients were assessed in a remission phase, at least 3 months from the last cluster attack, and without preventive medication.

Results: Side-to-side consistency between DPTs (r = 0.781, P < 0.001), roller-evoked pain on DPT (r = 0.586; P < 0.001), and PPTs (r = 0.874; P < 0.001) were found in men with CH. DPT was moderately, bilaterally, and side-to-side associated with PPTs (0.663 > r > 0.793, all P < 0.001). Men with CH had bilateral lower DPT and PPT and reported higher levels of roller-evoked pain (all P < 0.001) than headache-free controls.

Limitations: Only men with episodic CH were included.

Conclusions: This study supports that a dynamic pressure algometry is as valid as a static pressure algometry for assessing pressure pain sensitivity in patients with CH. Assessing both dynamic and static pain sensitivity may provide new opportunities for differentiated diagnostics.

Key Words: Cluster headache, dynamic pressure pain, pressure pain threshold.
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March 2020