Placebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can shape our sensory... Show morePlacebo and nocebo effects, positive and negative effects experienced after both real and sham interventions, putatively due to positive or negative outcome expectancies, can shape our sensory experience. Although placebo and nocebo effects are known to occur reliably in many individuals for sensations like pain and itch, our understanding of psychological learning processes and methodological factors that influence these effects remains limited. Chapters 2, 3, and 4 investigate this topic with meta-analysis, narrative review, and a behavioral study. Similarly, our characterization of the neural markers of nocebo effects is incomplete. A better grasp of how these effects form is necessary to contextualize them within the larger framework of bottom-up and top-down integration. Chapters 5, 6, and 7 investigate this topic in a series of EEG and fMRI studies. Advancing both psychological and neural accounts of placebo and nocebo effects will aid in applying findings from this field of study to everyday life; particularly in clinical settings, and potentially any setting in which expectations regarding one’s future experiences come into play. Show less
Carryover of previous treatment outcomes to subsequent medical treatment outcomes seems to be pervasive. The influence of a treatment history can generalize across treatments and across symptoms.... Show moreCarryover of previous treatment outcomes to subsequent medical treatment outcomes seems to be pervasive. The influence of a treatment history can generalize across treatments and across symptoms. These generalization effects in clinical practice have been studied experimentally in placebo and nocebo effects, which are beneficial and adverse effects that do not arise from active treatment components, respectively. The aim of this thesis was to answer the question of whether previously learned placebo and nocebo effects can generalize within and across somatosensory sensations. Additionally, the thesis also explored the role of individual characteristics as predictors (e.g., anxiety, stress, attention, catastrophizing) for the generalization of placebo and nocebo effects. The findings of the thesis have showed that placebo and nocebo effects can generalize within pain and itch modalities, but can not generalize from pain to itch and from itch to touch. The generalization effects of placebo and nocebo effects can not be predicted by psychological characteristics (e.g., anxiety- and stress symptoms) in healthy individuals. Moreover, the dissertation addresses the limitations of the work and directions for future research, as well as giving implications for clinic practice. Show less
Spekking, K.; Anink, J.; Boer, P. de; Bergstra, S.A.; Berg, J.M. van den; Schonenberg-Meinema, D.; ... ; Muller, P.C.E.H. 2023
BackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for... Show moreBackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up.ResultsPain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [ -0.34 (-0.55; -0.06)], CHQ Physical [ -0.42 (-0.72; -0.11)] and Psychosocial summary Score [ -0.42 (-0.77; -0.06)] were predictive of lower pain.ConclusionsTreatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain. Show less
Spekking, K.; Anink, J.; Boer, P. de; Bergstra, S.A.; Berg, J.M. van den; Schonenberg-Meinema, D.; ... ; Muller, P.C.E.H. 2023
BackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for... Show moreBackgroundThe aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.MethodsIn the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up.ResultsPain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [ -0.34 (-0.55; -0.06)], CHQ Physical [ -0.42 (-0.72; -0.11)] and Psychosocial summary Score [ -0.42 (-0.77; -0.06)] were predictive of lower pain.ConclusionsTreatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain. Show less
Binvignat, M.; Emond, P.; Mifsud, F.; Miao, B.; Courties, A.; Lefèvre, A.; ... ; Sellam, J. 2023
ObjectiveTo investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA).MethodsThe baseline serum concentration of 20 Tryptophan metabolites was measured in 416... Show moreObjectiveTo investigate host and gut-microbiota related Tryptophan metabolism in hand osteoarthritis (HOA).MethodsThe baseline serum concentration of 20 Tryptophan metabolites was measured in 416 HOA patients in a cross-sectional analysis of the DIGICOD cohort. Tryptophan metabolites levels, metabolite-ratios and metabolism pathway activation were compared between erosive (N = 141) and non-erosive HOA (N = 275) by multiple logistic regressions adjusted on age, BMI and sex. The association between Tryptophan metabolite levels and HOA symptoms was investigated by a Spearman's rank correlation analysis.ResultsFour serum Tryptophan metabolites, eight metabolite ratios and one metabolism pathway were associated with erosive HOA. Erosive HOA was negatively associated with Tryptophan (odds ratio (OR) = 0.41, 95% confidence interval [0.24–0.70]), indole-3-aldehyde (OR = 0.67 [0.51–0.90]) and 3-OH-anthranilic acid (OR = 1.32 [1.13–1.54]) and positively with 5-OH-Tryptophan levels (OR = 1.41 [1.13–1.77]). The pro-inflammatory kynurenine–indoleamine 2,3-dioxygenase pathway was upregulated in erosive HOA (OR = 1.60 [1.11–2.29]). Eleven metabolites were correlated with HOA symptoms and were mostly pain-related. Serotonin and N-acetyl serotonin levels were negatively correlated with number of tender joints. Indole-3-aldehyde level was negatively correlated and 3-OH-anthranilic acid, 3-OH-kynurenine and 5-OH-Tryptophan levels were positively correlated with number of patients-reported painful joints. Quinolinic acid and 3-OH-kynurenine levels correlated positively with AUSCAN pain.ConclusionsTryptophan metabolites disturbance is associated with erosive HOA and pain and emphasize the role of low-grade inflammation and gut dysbiosis in HOA. Show less
Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of... Show morePhysical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank - based on their perceived importance - known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors. Show less
Hoydonckx, Y.; Singh, M.; Gilron, I.; Khan, J.; Narouze, S.; Dahan, A.; ... ; Bhatia, A. 2023
BackgroundChronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to... Show moreBackgroundChronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-d-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion.MethodsA multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg−1 bolus followed by infusion of 1 mg. kg−1. h−1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusionDiscussionDespite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache. Show less
Meier, M.E.; Hagelstein-Rotman, M.; Ven, A.C. van de; Geest, I.C.M. van der; Donker, O.; Pichardo, S.E.C.; ... ; Appelman-Dijkstra, N.M. 2022
Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a... Show moreBackground: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observational study aimed to evaluate effects of 1 year of treatment in the FD/MAS care pathway in 2 tertiary clinics on QoL and pain, assessed by change in Short Form 36 and Brief Pain Inventory between baseline and follow-up. Patients completing baseline questionnaires < 1 year after intake were classified as new referrals, others as under chronic care. Results: 92 patients were included, 61 females (66%). 22 patients (24%) had monostotic disease, 16 (17%) isolated craniofacial FD, 27 (40%) polyostotic FD and 17 (19%) MAS. 26 were new referrals (28%) and 66 chronic patients (72%). Median age at baseline was 47 years (Q1-Q3 36-56). Skeletal burden correlated with baseline Physical Function (r(s) = - 0.281, p = 0.007). QoL was in all domains lower compared to the general population. New referrals reported clinically important differences (CID) over time in domains Physical Function (mean 67 & PLUSMN; SD24 to 74 & PLUSMN; 21, effect size (ES) 0.31, p = 0.020), Role Physical (39 & PLUSMN; 41 to 53 & PLUSMN; 43, ES 0.35, p = 0.066), Social Functioning (64 & PLUSMN; 24 to 76 & PLUSMN; 23, ES 0.49, p = 0.054), and Health Change (39 & PLUSMN; 19 to 53 & PLUSMN; 24, ES 0.76, p = 0.016), chronic patients in Physical Function (52 & PLUSMN; 46 to 66 & PLUSMN; 43, ES 0.31, p = 0.023) and Emotional Wellbeing (54 & PLUSMN; 27 to 70 & PLUSMN; 15, ES 0.59, p < 0.001). New referrals reported a CID of 1 point in maximum pain, average pain and pain interference, chronic patients reported stable scores. Change in pain interference and Role Physical were correlated (r(s) = - 0.472, p < 0.001). Patients with limited disease extent improved more than patients with severe disease. Patients receiving FD-related therapy had lower baseline scores than patients not receiving therapy and reported improvements in QoL after 1 year. Yet also patients without FD-related therapy improved in Physical Function. Conclusions: All FD-subtypes may induce pain and reduced QoL. A multidisciplinary care pathway for FD/MAS may improve pain and QoL, mainly in new referrals without MAS comorbidities with low baseline scores. Therefore, we recommend referral of patients with all subtypes of FD/MAS to specialized academic centers. Show less
Mitropoulos, A.; Bostrom, C.; Mattsson, M.; Kouidi, E.; Dimitroulas, T.; Liem, S.I.E.; ... ; Klonizakis, M. 2022
Background: Pain, related to Raynaud's phenomenon or digital ulceration, has been identified as very prevalent and debilitating symptoms of systemic sclerosis (SSc), both significantly affecting... Show moreBackground: Pain, related to Raynaud's phenomenon or digital ulceration, has been identified as very prevalent and debilitating symptoms of systemic sclerosis (SSc), both significantly affecting patients' quality of life (QoL). Pharmacological therapeutic strategies were found not to be sufficiently effective in the management of SSc-induced pain and fatigue, and evidence for exercise is scarce. As yet, the effects of a long-term, tailored exercise programme on pain and fatigue in patients with SSc have not been explored. In addition to pain and fatigue, this study aims to evaluate the effects of exercise on QoL, physical fitness, functional capacity, and vascular structure in people with SSc (PwSSc). Methods: This will be a multicentre (n = 6) randomised controlled clinical trial to assess the effect of a previously established, supervised 12-week combined exercise programme on pain and fatigue as compared to no exercise in PwSSc. The study will recruit 180 patients with SSc that will be allocated randomly to two groups. Group A will perform the exercise programme parallel to standard usual care and group B will receive usual care alone. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30-min high-intensity interval training (HIIT) (30-s 100% peak power output/30-s passive recovery) on an arm crank ergometer and 15 min of upper body circuit resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary outcomes of the study will be pain and fatigue assessed via questionnaires. Secondary outcomes include quality of life, structure of digital microvasculature, body composition, physical fitness, and functional capacity. Discussion: Data from this multi-centre research clinical trial will primarily be used to establish the effectiveness of a combined exercise protocol to improve pain and fatigue in SSc. In parallel, this study will be the first to explore the effects of long-term exercise on potential microvascular alterations assessed via NVC. Overall, this study will provide sufficient data to inform current clinical practice guidelines and may lead to an improvement of QoL for patients with SSc. Show less
Complex Regional Pain Syndrome (CRPS) is a severely disabling pain syndrome. Patients report a poorer quality of life than patients with other chronic pain conditions, particularly in the physical... Show moreComplex Regional Pain Syndrome (CRPS) is a severely disabling pain syndrome. Patients report a poorer quality of life than patients with other chronic pain conditions, particularly in the physical domains (chapter 2). Sex differences are small, although male patients experience a higher psychological burden than female CRPS patients (chapter 3).Considering the pathophysiology CRPS, we could not reproduce previous MRI findings of altered brain function and structure in rest (Chapter 4). We did find increased salience detecting during the application of a painful stimulus with opposite activation of brain regions involved in reducing the affected burden of pain (chapter 5). Lastly, cortical motor activations during motor tasks differ from previously published results in patients with functional movement disorders (chapter 6). Show less
Within the field of pain but especially neuropathic pain there is still much to be gained, as illustrated by the unmet medical need and limitedly efficacious drug treatments currently available. A... Show moreWithin the field of pain but especially neuropathic pain there is still much to be gained, as illustrated by the unmet medical need and limitedly efficacious drug treatments currently available. A key contributor to chronification of neuropathic pain is central sensitization, which may manifest clinically as hyperalgesia, a symptom non-existent in healthy individuals. Models that can induce hyperalgesia and tools that can appropriately assess altered nociceptive functioning in early-phase drug studies are sought-after, as they may aid in examining the potential of drugs as (neuropathic) pain treatment. Continuing efforts are made to expand and improve our knowledge in this field. This thesis describes our contribution, and was based on two main objectives. One was to develop and validate methods for early-phase clinical drug studies with improved accuracy or resemblance to clinical pathophysiology, to improve the evaluation of a drug’s mechanism of action and analgesic potential. The other objective was to actually test novel drugs that are proposed to have superior clinical utility, using methods we believed to be appropriate for evaluating those drugs’ analgesic effects. Show less
This PhD research dealt with neurobiological and behavioral aspects of pain. Previous research has demonstrated that pain sensitivity can be worsened as a result of learned negative expectations, a... Show moreThis PhD research dealt with neurobiological and behavioral aspects of pain. Previous research has demonstrated that pain sensitivity can be worsened as a result of learned negative expectations, a phenomenon termed nocebo hyperalgesia –a counterpart to placebo analgesia. This PhD dissertation describes neuroimaging and biobehavioral experimental studies as well as a review and a meta-analysis concerned with such learned effects on pain. The research adds to a growing literature that has been challenging antiquated understandings of pain as a bottom-up process. We conducted a series of biobehavioral studies to further our understanding of how bottom-up pain signaling can be influenced by top-down processing. We examined the types of experiences, such as receiving negative information or experiencing a negative effect first-hand, that may lead to stronger nocebo effects. Behavioral paradigms were used to model real-life pain experiences, through validated methods, novel learning manipulations, as well as a close examination of emotional correlates such as fear. Concurrently, innovative neuroscientific methods –including pharmacological manipulations– were used to examine the biobehavioral underpinnings of learned nocebo responses. Our findings add to the growing knowledgebase from the field of nocebo hyperalgesia, demonstrating that learning by experience can decisively influence the processing and perception of noxious stimuli. Show less
Loef, M.; Stadt, L. van de; Bohringer, S.; Bay-Jensen, A.C.; Mobasheri, A.; Larkin, J.; ... ; Kloppenburg, M. 2022
Objective: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. Design: We used... Show moreObjective: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. Design: We used baseline data from the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort, comprising persons with knee OA fulfilling the clinical American College of Rheumatology classification criteria. Radiographic knee and hand OA severity was quantified with Kellgren-Lawrence sum scores. Knee and hand pain and function were assessed with validated questionnaires. We quantified fasted plasma higher order lipids and oxylipins with liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based platforms. Using penalised linear regression, we assessed the variance in OA severity explained by lipidomics, with adjustment for clinical covariates (age, sex, body mass index (BMI) and lipid lowering medication), measurement batch and clinical centre. Results: In 216 participants (mean age 66 years, mean BMI 27.3 kg/m2, 75% women) we quantified 603 higher order lipids (triacylglycerols, diacylglycerols, cholesteryl esters, ceramides, free fatty acids, sphingomyelins, phospholipids) and 28 oxylipins. Lipidomics explained 3% and 2% of the variance in radiographic knee and hand OA severity, respectively. Lipids were not associated with knee pain or function. Lipidomics accounted for 12% and 6% of variance in hand pain and function, respectively. The investigated OA severity outcomes were associated with the lipidomic fraction of bound and free arachidonic acid, bound palmitoleic acid, oleic acid, linoleic acid and docosapentaenoic acid. Conclusions: Within the APPROACH cohort lipidomics explained a minor portion of the variation in OA severity, which was most evident for the outcome hand pain. Our results suggest that eicosanoids may be involved in OA severity. (c) 2022 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. Show less
Meent, M.M. van de; Appelman-Dijkstra, N.M.; Wetselaar-Glas, M.J.M.; Pichardo, S.E.C.; Merkesteyn, J.P.R. van 2022
This study aims to evaluate short-term and long-term results of bisphosphonate therapy in patients with diffuse sclerosing osteomyelitis/tendoperiostitis (DSO/TP) of the mandible. Eighteen patients... Show moreThis study aims to evaluate short-term and long-term results of bisphosphonate therapy in patients with diffuse sclerosing osteomyelitis/tendoperiostitis (DSO/TP) of the mandible. Eighteen patients (12 female, 6 male) aged 34.8 +/- 22.2 years with DSO/TP of the mandible that were treated with bisphosphonates were included. In 16 patients, the bisphosphonate treatment led to remission with decrease of symptoms (pain, swelling of the cheek, trismus, tenderness of masticatory muscles) with a follow-up period of 4.5 (0.8-11.9) years between start of bisphosphonate treatment and latest follow-up consult. Of these, three patients were still in need of regular bisphosphonate therapy. Two patients were lost to follow-up. Bisphosphonate therapy is a treatment option for DSO/TP of the mandible that is associated with a high chance of remission of symptoms. Within the limitations of the study it seems that this treatment might be an effective second step in DSO/TP refractory to conservative treatment. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/). Show less
The primary aim of this thesis was to investigate the complex relationship between pain, neuropsychiatric symptoms, and ADL functioning in persons with dementia. Furthermore, we studied the... Show moreThe primary aim of this thesis was to investigate the complex relationship between pain, neuropsychiatric symptoms, and ADL functioning in persons with dementia. Furthermore, we studied the psychometric properties of a new and universal observational pain assessment instrument Pain Assessment In Impaired Cognition: PAIC.The results of this thesis show that pain in nursing home residents with dementia is related to a decline in ADL functions, independent of dementia severity. Specifically, a decline in the ADL activities transferring and bathing.Additionally, the psychometric evaluation of the PAIC presented in this thesis not only results in a promising measurement instrument, but also provides useful information for the development and improvement of educational programmes that contribute to the utilization of the PAIC15. Show less
Chronic pain is frequently reported after total hip and knee arthroplasties (THA/TKA) in osteoarthritis (OA) patients. We investigated if severity of acute postoperative pain following THA/TKA in... Show moreChronic pain is frequently reported after total hip and knee arthroplasties (THA/TKA) in osteoarthritis (OA) patients. We investigated if severity of acute postoperative pain following THA/TKA in OA patients was associated with pain during the first postoperative year. From an observational study, OA patients scheduled for primary THA/TKA (June 2012-December 2017) were included from two hospitals in the Netherlands. Acute postoperative pain scores were collected within 72 h postoperatively and categorized as no/mild (NRS <= 4) or moderate/severe (NRS > 4). Pain was assessed preoperatively, 3, 6 and 12 months postoperatively using the HOOS/KOOS subscale pain. With Multilevel Mixed-effects-analyses, we estimated associations between acute and chronic pain until one year postoperative, adjusted for confounders and including an interaction term (Time*Acute pain). 193 THA and 196 TKA patients were included, 29% of THA and 51% of TKA patients reported moderate/severe pain acutely after surgery. In the THA group, the difference in pain at 3 months between the no/mild and moderate/severe groups, was approximately six points, in favor of the no/mild group (95% CI [-12.4 to 0.9]) this difference became smaller over time. In the TKA group we found similar differences, with approximately four points (95% CI [-9.6 to 1.3]) difference between the no/mild and moderate/severe group at 6 months, this difference attenuated at 12 months. No association between severity of acute postoperative pain and pain during the first postoperative year was found. These findings suggest that measures to limit acute postoperative pain will likely not impact development of chronic pain. Show less
Berg, B. van den; Hijma, H.J.; Koopmans, I.; Doll, R.J.; Zuiker, R.G.J.A.; Groeneveld, G.J.; Buitenweg, J.R. 2022
Sleep deprivation has been shown to increase pain intensity and decrease pain thresholds in healthy subjects. In chronic pain patients, sleep impairment often worsens the perceived pain intensity.... Show moreSleep deprivation has been shown to increase pain intensity and decrease pain thresholds in healthy subjects. In chronic pain patients, sleep impairment often worsens the perceived pain intensity. This increased pain perception is the result of altered nociceptive processing. We recently developed a method to quantify and monitor altered nociceptive processing by simultaneous tracking of psychophysical detection thresholds and recording of evoked cortical potentials during intra-epidermal electric stimulation. In this study, we assessed the sensitivity of nociceptive detection thresholds and evoked potentials to altered nociceptive processing after sleep deprivation in an exploratory study with 24 healthy male and 24 healthy female subjects. In each subject, we tracked nociceptive detection thresholds and recorded central evoked potentials in response to 180 single- and 180 double-pulse intra-epidermal electric stimuli. Results showed that the detection thresholds for single- and double-pulse stimuli and the average central evoked potential for single-pulse stimuli were significantly decreased after sleep deprivation. When analyzed separated by sex, these effects were only significant in the male population. Multivariate analysis showed that the decrease of central evoked potential was associated with a decrease of task-related evoked activity. Measurement repetition led to a decrease of the detection threshold to double-pulse stimuli in the mixed and the female population, but did not significantly affect any other outcome measures. These results suggest that simultaneous tracking of psychophysical detection thresholds and evoked potentials is a useful method to observe altered nociceptive processing after sleep deprivation, but is also sensitive to sex differences and measurement repetition. Show less
This thesis aims to describe certain novel approaches and pharmacological interventions in the treatment of acute and chronic pain. It demonstrates that the efficacy of the mu-opioid receptor... Show moreThis thesis aims to describe certain novel approaches and pharmacological interventions in the treatment of acute and chronic pain. It demonstrates that the efficacy of the mu-opioid receptor agonist and noradrenaline reuptake inhibitor tapentadol in the treatment of chronic pain is highest in specific patient phenotypes. This highlights the importance of patient phenotyping to get a detailed indication of the characteristics of the different aspects of the pain syndrome (such as involvement and activity of excitatory versus inhibitory pathways) without the need for knowledge on underlying mechanisms or related illnesses. Additionally, it demonstrates that treatment with the non-conventional treatment option cannabis shows potential but efficacy in the chosen patient population was limited. This thesis is also designated to treatment of acute pain with sublingual sufentanil and a non-opioid alternative option (ice-popsicle). Both show efficacy and seem possible alternatives as part of the multimodal therapy of acute pain. Show less
Trigt, V.R. van; Pelsma, I.C.M.; Kroon, H.M.; Pereira, A.M.; Meulen, C. van der; Kloppenburg, M.; ... ; Claessen, K.M.J.A. 2021
Purpose Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are... Show morePurpose Pain is a common symptom of acromegaly, impairing health-related quality of life (HR-QoL) significantly despite long-term disease remission. Neuropathic-like pain (NP-like) symptoms are invalidating, with great impact on HR-QoL. Studies characterizing or investigating the etiology of pain in acromegaly are scarce. Therefore, we aimed to assess NP-like symptoms in a cohort of controlled acromegaly patients. Methods Forty-four long-term controlled acromegaly patients (aged 62.6 +/- 12.6 years; 56.8% female) were included in this cross-sectional study. NP-like symptoms were assessed using the validated painDETECT questionnaire. Patients were divided in three probability-based NP-like symptoms categories based on the total score (range 0-35): unlikely (<= 12), indeterminate (13-18) and likely (>= 19). HR-QoL (physical component score (PCS), and mental component score (MCS)), and self-reported pain were assessed using Short Form-36 (SF-36). Potential risk factors were determined using linear regression analyses. Results Self-reported pain was reported by 35 patients (79.5%). Likely NP-like symptoms were present in 4/44 patients (9.1%), and indeterminate NP-like symptoms in 6/44 patients (13.6%). All patients with likely NP-like symptoms were female. Higher painDETECT scores were negatively associated with HR-QoL (PCS: r = - 0.46, P = 0.003; MCS: r = - 0.37, P = 0.018), and SF-36 pain scores (r = - 0.63, P < 0.0001). Female sex was a risk factor for NP-like symptoms. Conclusions Pain was prevalent in controlled acromegaly patients, whereas NP-like symptoms were relatively infrequent, and only observed in females. NP-like symptoms were associated with lower HR-QoL in acromegaly. Since specific analgesic therapy is available, awareness for characterization, increased understanding, and clinical trials regarding neuropathic pain identification and treatment in acromegaly patients are warranted. Show less
This dissertation covered several relevant cycles of placebo research with the main aim to optimize placebo effects in medical contexts. Firstly, a literature review described how the immune system... Show moreThis dissertation covered several relevant cycles of placebo research with the main aim to optimize placebo effects in medical contexts. Firstly, a literature review described how the immune system can be impacted by placebo effects and their underlying learning theories. In the following chapter, these learning theories were integrated to form an optimal research design by means of pharmacological conditioning to fit a specific patient group: children with juvenile idiopathic arthritis. Secondly, this dissertation focused on developing placebo information strategies to harness placebo beliefs and educate persons about the relevancy of placebo effects in practice. These insights are valuable because treatment expectations can have a positive or negative effect on treatment outcomes. Finally, insights from placebo learning theories and placebo information strategies were combined in an integrative experimental research design. This research design employed a more ethical form of placebo use because participants were made aware of placebos, called open-label placebos. In this last study we demonstrated that open-label placebo analgesia can be induced by combining learning theories and placebo information strategies. Altogether, this dissertation provided insights in learning mechanisms, communication strategies, and research paradigms that involve the optimization of placebo effects in medical context. Show less
