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Nocebo hyperalgesia refers to increases in perceived pain that putatively result from negative expectations regarding a nocebo stimulus (eg, an inert treatment, compared with no treatment). The precise cognitive-emotional factors contributing to the origins of nocebo effects are poorly understood. We aimed to test the effects of experimentally induced pain-related fear on the acquisition and extinction of nocebo hyperalgesia in healthy participants (N = 72). Acquisition and extinction of nocebo hyperalgesia were compared between a group receiving standard nocebo conditioning (Control group) and 2 groups receiving distinct fear inductions: high intensity of pain stimulations (High-pain group) or a threat manipulation (High-threat group). During nocebo acquisition, the Control and High-threat groups were administered thermal pain stimulations of moderate intensity paired with sham electrical stimulation (nocebo trials), whereas high pain intensity was administered to the High-pain group. During extinction, equivalent pain intensities were administered across all trials. Pain-related fear was measured by eyeblink startle electromyography and self-report. Nocebo hyperalgesia occurred in all groups. Nocebo effects were significantly larger in the High-pain group than those in the Control group. This effect was mediated by self-reported fear, but not by fear-potentiated startle. Groups did not differ in the extinction rate. However, only the High-pain group maintained significant nocebo responses at the end of extinction. Anticipatory pain-related fear induced through a threat manipulation did not amplify nocebo hyperalgesia. These findings suggest that fear of high pain may be a key contributor to the amplification of nocebo hyperalgesia, only when high pain is experienced and not when it is merely anticipated.
Learn More >Occipital nerve stimulation (ONS) is shown to be effective in treating various forms of headache. Most studies describe the treatment of occipital neuralgia (ON), but in many patients, the clinical description could also correspond to cervicogenic headache (CGH) or occipital migraine (OM). These different entities (ON, CGH, and OM) may be grouped together under the term occipital headaches.
Learn More >Background and aims Few studies have reported the long-term impact of chronic pain on health care utilization. The primary aim of this study was to investigate if chronic musculoskeletal pain was associated with health care utilization in the general population in a 21-year follow-up of a longitudinal cohort. The secondary aim was to identify and describe factors that characterize different long-term trajectories of health care utilization. Methods A prospective cohort design with a baseline sample of 2,425 subjects (aged 20-74). Data were collected by self-reported questionnaires, and three time points (1995, 2007, and 2016) were included in the present 21-year follow up study. Data on health care utilization were dichotomized at each time point to either high or low health care utilization. High utilization was defined as >5 consultations with at least one health care provider, or ≥1 consultation with at least 3 different health care providers during the last 12 months. Low health care utilization was defined as ≤5 consultations with one health care provider and <3 consultations with different health care providers. The associations between baseline variables and health care utilization in 2016 were analyzed by multiple logistic regression. Five different trajectories for health care utilization were identified by visual analysis, whereof four of clinical relevance were included in the analyses. Results Baseline predictors for high health care utilization at the 21-year follow-up in 2016 were chronic widespread pain (OR: 3.2, CI: 1.9-5.1), chronic regional pain (OR:1.8, CI: 1.2-2.6), female gender (OR: 2.0, CI: 1.4-3.0), and high age (OR: 1.6, CI:0.9-2.9). A stable high health care utilization trajectory group was characterized by high levels of health care utilization, and a high prevalence of chronic pain at baseline and female gender (n = 23). A stable low health care utilization trajectory group (n = 744) was characterized by low health care utilization, and low prevalence of chronic pain at baseline. The two remaining trajectories were: increasing trajectory group (n = 108), characterized by increasing health care utilization, chronic pain at baseline and female gender, and decreasing trajectory group (n = 107) characterized by decreasing health care utilization despite a stable high prevalence of chronic pain over time. Conclusions The results suggest that chronic pain is related to long-term health care utilization in the general population. Stable high health care utilization was identified among a group characterized by female gender and a report of chronic widespread pain. Implications This cohort study revealed that chronic widespread pain predicted high health care utilization over a 21-year follow-up period. The results indicate the importance of early identification of musculoskeletal pain to improve the management of pain in the long run.
Learn More >Background and aims Evidence for analgesic effects of oral alcohol consumption on heat pain has recently been documented in a placebo-controlled, randomized and double-blind design. We aimed at further investigating these effects and now set the focus on pain threshold and the ratings of supra-threshold pain to cover most of the pain range. Moreover, we now firstly evaluated sex differences in these effects. Methods We investigated 41 healthy participants (22 females) in a randomized, double-blind and placebo-controlled design and targeted two different moderate breath-alcohol levels of 0.06% and 0.08%. Before and after an alcoholic or placebo drink, contact heat was applied at the forearm. Subjects evaluated pain threshold (method of adjustment) and rated pain intensity and pain unpleasantness of supra-threshold stimuli (intensity: threshold +3 °C; duration: 5 s). Results Analgesic effects taking the form of increased pain thresholds were found after both alcohol doses, surprisingly with more pronounced effects for the lower dose. While the high alcohol dose exerted small analgesic effects on pain intensity ratings (i.e. decrease), slightly increased ratings of pain intensity and pain unpleasantness after the low alcohol dose rather suggest pain enhancement. Alcohol did not affect intensity vs. unpleasantness ratings differentially. We found no evidence for sex differences in any of these effects. Conclusions Overall, acute alcohol effects on pain were subtle. Our findings suggest that while low alcohol doses already exert analgesic effects on pain threshold, stronger doses are required for pain reduction on supra-threshold pain levels. Furthermore, sex differences could not be detected within our experimental paradigm but should be further explored in future research. Implications Analgesic effects of sub-toxic alcohol doses – as normally occurring during social drinking – might be weak; however, susceptibility to pain relieving effects of alcohol might be a risk factor for the use of alcohol as self-medication in acute pain states.
Learn More >Post-traumatic headache (PTH) is one of the most frequent symptoms following mild traumatic brain injury (mTBI). Neuroimaging studies implicate hypothalamic function connectivity (FC) disruption as an important factor in pain disorders. However, it is unknown whether there are alterations in the hypothalamus-based resting state FC within PTH following mTBI at the acute stage and its relationship with headache symptom measurement.
Learn More >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.
Learn More >Fibromyalgia (FM) is a complex pain condition where the pathophysiological and molecular mechanisms are not fully elucidated. The primary aim of this study was to investigate the plasma proteome profile in women with FM compared to controls. The secondary aim was to investigate if plasma protein patterns correlate with the clinical variables pain intensity, sensitivity, and psychological distress. Clinical variables/background data were retrieved through questionnaires. Pressure pain thresholds (PPT) were assessed using an algometer. The plasma proteome profile of FM (n = 30) and controls (n = 32) was analyzed using two-dimensional gel electrophoresis and mass spectrometry. Quantified proteins were analyzed regarding group differences, and correlations to clinical parameters in FM, using multivariate statistics. Clear significant differences between FM and controls were found in proteins involved in inflammatory, metabolic, and immunity processes. Pain intensity, PPT, and psychological distress in FM had associations with specific plasma proteins involved in blood coagulation, metabolic, inflammation and immunity processes. This study further confirms that systemic differences in protein expression exist in women with FM compared to controls and that altered levels of specific plasma proteins are associated with different clinical parameters.
Learn More >The aim of this study is to estimate a minimal clinically important difference (MCID) and a minimal detectable change (MDC) of the 12-item WHODAS 2.0 amongst patients with chronic musculoskeletal pain.
Learn More >Objectives Contemporary fear-avoidance models of chronic pain posit that fear of pain, and overgeneralization of fear to non-threatening stimuli is a potential pathway to chronic pain. While increasing experimental evidence supports this hypothesis, a comprehensive investigation requires testing in multiple modalities due to the diversity of symptomatology among individuals with chronic pain. In the present study we used an established tactile fear conditioning paradigm as an experimental model of allodynia and spontaneous pain fluctuations, to investigate whether stimulus generalization occurs resulting in fear of touch spreading to new locations. Methods In our paradigm, innocuous touch is presented either paired (predictable context) or unpaired (unpredictable context) with a painful electrocutaneous stimulus (pain-US). In the predictable context, vibrotactile stimulation to the index or little finger was paired with the pain-US (CS+), whilst stimulation of the other finger was never paired with pain (CS-). In the unpredictable context, vibrotactile stimulation to the index and little fingers of the opposite hand (CS1 and CS2) was unpaired with pain, but pain-USs occurred unpredictable during the intertrial interval. During the subsequent generalization phase, we tested the spreading of conditioned responses (self-reported fear of touch and pain expectancy) to the (middle and ring) fingers between the CS+ and CS-, and between the CS1 and CS2. Results Differential fear acquisition was evident in the predictable context from increased self-reported pain expectancy and self-reported fear for the CS + compared to the CS-. However, expectancy and fear ratings to the novel generalization stimuli (GS+ and GS-) were comparable to the responses elicited by the CS-. Participants reported equal levels of pain expectancy and fear to the CS1 and CS2 in the unpredictable context. However, the acquired fear did not spread in this context either: participants reported less pain expectancy and fear to the GS1 and GS2 than to the CS1 and CS2. As in our previous study, we did not observe differential acquisition in the startle responses. Conclusions Whilst our findings for the acquisition of fear of touch replicate the results from our previous study (Biggs et al., 2017), there was no evidence of fear generalization. We discuss the limitations of the present study, with a primary focus on procedural issues that were further investigated with post-hoc analyses, concluding that the present results do not show support for the hypothesis that stimulus generalization underlies spreading of fear of touch to new locations, and discuss how this may be the consequence of a context change that prevented transfer of acquisition.
Learn More >High-intensity training (HIT) improves rehabilitation outcomes such as functional disability and physical performance in several chronic disorders. Promising results were also found in chronic nonspecific low back pain (CNSLBP). However, the impact of different exercise modes on HIT effectiveness in CNSLBP remains unclear. Therefore, this study evaluated the effectiveness of various HIT exercise modes and compared differences between these modes, on pain intensity, disability, and physical performance, as a therapeutic intervention for persons with CNSLBP. In a randomized comparative trial, consisting of a 12-week program, persons with CNSLBP were divided into four HIT groups, i.e., cardiorespiratory interval training coupled with either general resistance training, core strength training, combined general resistance and core strength training, or mobility exercises. Before and after the program, the Numeric Pain Rating Scale (NPRS), Modified Oswestry Disability Index (MODI), and Patient Specific Functioning Scale (PSFS) were recorded, and a cardiopulmonary exercise test (VOmax, cycling time) and isometric trunk strength test (maximum muscle torque) were performed. Eighty participants (mean age: 44.0 y, 34 males) were included. Improvements were found within all groups after the HIT programs and ranged from -39 to -57% on the NPRS, +27 to +64% on the MODI, +38 to +89% on the PSFS, +7 to +14% on VOmax, and +11 to +18% on cycling time. No differences between groups were found. High-intensity cardiorespiratory interval training improves CNSLBP rehabilitation outcomes when performed with other HIT exercise modes or mobility exercises. Hence, when setting up an exercise therapy program in CNSLBP rehabilitation, various HIT modes can be considered as therapy modalities.
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