Linn Karlsson

Chronic widespread pain: increased glutamate and lactate concentrations in the trapezius muscle and plasma.

Background:Chronic widespread pain (CWP), including fibromyalgia syndrome (FM), is associated with prominent negative consequences. CWP has been associated with alterations in the central processing of nociception. Whereas some researchers consider CWP/FM as a central hyperexcitability pain condition, others suggest that the central alterations are maintained by peripheral nociceptive input. Microdialysis can be used in vivo to study muscle alterations in chronic myalgia. Aim:The aim of the study was to investigate the plasma and interstitial concentrations of metabolites and algesics in the trapezius muscle of women with CWP and in pain-free women (CON). Materials and Methods:Seventeen women with CWP and 24 CON went through a clinical examination and completed a questionnaire; the pressure pain thresholds in the upper and lower extremities were registered. Microdialysis was conducted in the trapezius muscle, and a blood sample was drawn. Muscle blood flow, interstitial muscle concentrations, and plasma concentrations of lactate, pyruvate, glutamate, glucose, and glycerol (not in the plasma) were determined. Results:CWP patients had significantly increased interstitial muscle (P=0.02 to 0.001) and plasma (P=0.026 to 0.017) concentrations of lactate and glutamate. No significant differences existed in blood flow between CWP and CON. The interstitial concentrations—but not the plasma levels—of glutamate and lactate correlated significantly with aspects of pain such as pressure pain thresholds of the trapezius (R2=0.22) and tibialis anterior (R2=0.18) and the mean pain intensity (R2=0.10) in CWP but not in CON. Conclusions:The present study supports the suggestion that aspects of pain and central alterations in CWP/FM are influenced by peripheral tissue alterations.

High Levels of N-Palmitoylethanolamide and N-Stearoylethanolamide in Microdialysate Samples from Myalgic Trapezius Muscle in Women

Background N-acylethanolamines (NAEs) are endogenous compounds that regulate inflammation and pain. These include the cannabinoid ligand anandamide (AEA) and the peroxisome proliferator-activated receptor-α ligand palmitoylethanolamide (PEA). Little is known as to the levels of NAEs in pain states in human, particularly in the skeletal muscle. The aim of this study was to investigate the levels of these lipid mediators in muscle dialysate from women with chronic neck-/shoulder pain compared to healthy controls. Methods Eleven women with chronic neck-/shoulder pain and eleven healthy women participated in this study. All participants went through microdialysis procedures in the trapezius muscle. Muscle dialysate samples were collected during four hours and analysed by nano liquid chromatography tandem mass spectrometry (nLC-MS/MS). Results We were able to detect AEA, PEA, N-stearoylethanolamine (SEA) and 2-arachidonoylglycerol (2-AG) in a single chromatographic run. Of the NAEs studied, PEA and SEA were clearly detectable in the muscle microdialysate samples. The muscle dialysate levels of PEA and SEA were significantly higher in myalgic subjects compared to healthy controls. Conclusion This study demonstrates that microdialysis in combination with mass spectrometry can be used for analysing NAEs in human muscle tissue regularly over time. Furthermore the significant group differences in the concentration of PEA and SEA in this study might fill an important gap in our knowledge of mechanisms in chronic myalgia in humans. In the long run this expanded understanding of nociceptive and anitinociceptive processes in the muscle may provide a base for ameliorating treatment and rehabilitation of pain.

Evaluation of pain and function after two home exercise programs in a clinical trial on women with chronic neck pain - with special emphasises on completers and responders

BackgroundDifferent types of exercises can help manage chronic neck pain. Supervised exercise interventions are widely used, but these protocols require substantial resources. The aim of this trial, which focused on adherence, was to evaluate two home exercise interventions.MethodsThis parallel group randomized controlled trial included 57 women randomly allocated into two groups – a strength training group (STRENGTH, 34 subjects) and a stretching group (STRETCH, 23 subjects). The interventions focused on the neck and shoulder muscles and lasted for 12 months. The STRENGTH group performed weight training and ended each session with stretching exercises. These stretching exercises constituted the entirety of the STRETCH group’s training session. Both groups were instructed to exercise three times per week. All the participants kept an exercise diary. In addition, all participants were offered support via phone and e-mail. The primary outcomes were pain intensity and function. The trial included a four- to six-month and a twelve-month follow-up. A completer in this study exercised at least 1,5 times per week during eight unbroken weeks. A responder in this study reported clinically significant improvements on pain and function. The statistical analyses used the Mann Whitney U-test, Wilcoxon signed-rank test, and X2 test.ResultsAt four- to six-months, the numbers of completers were 19 in the STRENGTH group and 17 in the STRETCH group. At twelve months, the corresponding numbers were 11 (STRENGTH) and 10 (STRETCH). At four- to six-months, the proportions of subjects reporting clinically important changes (STRENGTH and STRETCH) were for neck pain: 47% and 41%, shoulder pain: 47% and 47%, function: 37% and 29%. At twelve months, the corresponding numbers were for neck pain: 45% and 40%, shoulder pain: 55% and 50%, function: 55% and 20%.ConclusionsNo differences in the two primary outcomes between the two interventions were found, a finding that may be due to the insufficient statistical power of the study. Both interventions based on home exercises improved the two primary outcomes, but the adherences were relatively low. Future studies should investigate ways to improve adherence to home exercise treatments.Trial registrationClinicalTrials.gov Id: NCT01876680

Intramuscular pain modulatory substances before and after exercise in women with chronic neck pain

In peripheral tissue, several substances influence pain and pain modulation. Exercise has been found to decrease pain and improve function for chronic pain conditions, but how and why exercise produces beneficial effects remains unclear. This study investigates whether aspects of pain and concentrations of substances with algesic, analgesic and metabolic functions differ between women with chronic neck shoulder pain (CNSP) and healthy women (CON) and whether changes are found after an exercise intervention for CNSP.

Relative recovery over time - an in vivo microdialysis study of human skeletal muscle.

Abstract Background. The microdialysis technique is a method for sampling endogenous molecules from the interstitial compartments of varying tissues and relies on diffusion of molecules between the tissue and a perfusate via a membrane. Such samples do not allow determination of the true interstitial concentration but only a certain percentage. This gives rise to one of the most crucial parameter that needs to be considered for a dependable microdialysis; the relative recovery. Relative recovery states the efficiency of which an analyte is extracted from its external medium. Aim. To investigate the relative recovery of small molecules (< 20 kDa) such as lactate, fluid recovery and the reproducibility of the relative recovery at group and individual level of the microdialysis technique applied in muscle. Materials and methods. Using in vivo microdialysis of the trapezius muscle of 65 women from two separate occasions 4–6 months apart. Relative recovery of small molecules was measured from samples collected every 20 min during a period of 220 min. Results. Good reproducibility at group level of catheters with cut-offs 100 and 20kDa were found. Furthermore, there was a high and steady relative recovery with an overall good fluid recovery. Poor reproducibility was found at the individual level for both catheters. Conclusions. This study demonstrates that when using microdialysis in skeletal muscle relative recovery is stable over time and is not affected by low-force exercise. Although there is a good reproducibility at group level this is not the case at the individual level. Thus in vivo, the relative recovery should be determined for each test subject and at each test occasion.

Effects of two different specific neck exercise interventions on palmitoylethanolamide and stearoylethanolamide concentrations in the interstitium of the trapezius muscle in women with chronic neck shoulder pain

PURPOSE Chronic neck/shoulder pain (CNSP) is one of the most common pain conditions. The understanding of mechanisms, including the peripheral balance between nociceptive and antinociceptive processes, is incomplete. N-acylethanolamines (NAEs) are a class of endogenous compounds that regulate inflammation and pain. The aim of this study was to investigate the levels of two NAEs: the peroxisome proliferator-activated receptor type-α ligand palmitoylethanolamide (PEA) and stearoylethanolamide (SEA) in the muscle interstitium of the trapezius muscle in women with CNSP randomized to two different neck specific training programs and in a healthy pain-free control group (CON). MATERIALS AND METHODS Fifty-seven women with CNSP were randomized to strength + stretch or stretch alone exercise programs. Twenty-nine subjects underwent microdialysis procedure before and after 4-6 months of exercise. Twenty-four CON subjects underwent microdialysis procedure before and after 4-6 months without any intervention in between. Microdialysate samples were collected from the trapezius muscle and analyzed by mass spectrometry for PEA and SEA levels. RESULTS PEA and SEA levels were significantly higher in CNSP patients compared with CON. PEA was significantly higher in CNSP than in CON after both training programs. SEA was significantly higher in CNSP than in CON after stretch alone but not after strength + stretch training. A significant positive correlation was found between changes in pain intensity and in SEA levels in the strength + stretch group, but not in the stretch alone group. CONCLUSION Our results indicate that exercise interventions differentially affect the levels of the bioactive lipids PEA and SEA in the interstitium of the trapezius muscle in women with CNSP.

Associations between psychological factors and the effect of home-based physical exercise in women with chronic neck and shoulder pain

Background: Exercise is often used in the treatment of chronic neck and shoulder muscle pain. It is likely that psychological aspects have an impact on the results of exercise-based treatments. Objectives: (1) To examine the associations between psychological factors and the effect of a home-based physical exercise intervention. (2) To examine differences in psychological factors at baseline between (a) subjects who continued in the trial and those who did not and (b) subjects who completed the intervention and those who did not. Method: A total of 57 women with chronic neck and shoulder pain were included in a home-based exercise intervention trial. Pain intensity, disability, and psychological factors (anxiety and depression symptoms, catastrophizing, fear-avoidance beliefs, self-efficacy, and pain acceptance) were measured at baseline, after 4–6 months, and after 1 year of exercise. Associations between the psychological factors and changes in pain intensity and disability were analysed, as well as differences in psychological factors at baseline between subjects who continued in and completed the intervention, and those who did not. Results: Associations between positive changes in pain intensity and disability were found for low fear-avoidance beliefs and low-pain self-efficacy at baseline. In addition, fear-avoidance beliefs at baseline were higher in the subjects who dropped out of the intervention than in those who continued. Pain acceptance at baseline was higher in the subjects who completed the intervention at the end of the trial. Conclusion: Particularly, fear-avoidance beliefs and pain self-efficacy should be taken into consideration when implementing home-based physical exercise as treatment for chronic neck pain. In addition, high pain acceptance might improve the adherence to prescribed exercise.

Experiences and attitudes about physical activity and exercise in patients with chronic pain: a qualitative interview study

Purpose The purpose of this study was to describe how patients with chronic pain experience physical activity and exercise (PA&E). Method This qualitative interview study included 16 women and two men suffering from chronic pain and referred to a multimodal pain rehabilitation program. Semi-structured interviews were conducted and qualitative content analysis was used to analyze the interviews. Results One main theme emerged: “To overcome obstacles and to seize opportunities to be physically active despite chronic pain.” This main theme was abstracted from five themes: “Valuing a life with physical activity,” “Physical activity and exercise – before and after pain,” “A struggle – difficulties and challenges,” “The enabling of physical activity,” and “In need of continuous and active support.” Conclusion Although these participants valued PA&E, they seldom achieved desirable levels, and performance of PA&E was undermined by difficulties and failure. The discrepancy between the intention to perform physical activity and the physical activity accomplished could be related to motivation, self-efficacy, and action control. The participants desired high-quality interaction with healthcare providers. The findings can be applied to chronic pain rehabilitation that uses PA&E as treatment.