pain – Page 8 – American ME and CFS Society

Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia

Abstract:

PURPOSE: The purpose of this study was to conduct a longitudinal examination of cognitive complaints and functional status in patients with chronic fatigue syndrome (CFS) alone and those who also had fibromyalgia (CFS/FM).

METHODS: A total of 93 patients from a tertiary care fatigue clinic were evaluated on four occasions, each 6 months apart. Each evaluation included a tender point assessment, and self-reported functional status and cognitive complaints.

RESULTS: Patients with CFS/FM reported significantly worse physical functioning, more bodily pain, and more cognitive difficulties (visuo-perceptual ability and verbal memory) than patients with CFS alone. Over time, bodily pain decreased only for participants with CFS alone. Verbal memory problems were associated with more bodily pain for both patient groups, whereas visuo-perceptual problems were associated with worse functional status for patients with CFS alone.

CONCLUSIONS: This study adds to the literature on functional status, longitudinal course, and cognitive difficulties among patients with CFS and those with CFS and FM. The results suggest that patients with CFS/FM are more disabled, have more cognitive complaints, and improve more slowly over time than patients with CFS alone. Specific cognitive difficulties are related to worse functional status, which supports the addition of cognitive difficulties to the FM case criteria.

Source: Schmaling KB, Betterton KL. Neurocognitive complaints and functional status among patients with chronic fatigue syndrome and fibromyalgia. Qual Life Res. 2016 May;25(5):1257-63. doi: 10.1007/s11136-015-1160-y. Epub 2015 Oct 15. https://www.ncbi.nlm.nih.gov/pubmed/26471263

Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter

Abstract:

BACKGROUND: In addition to the frequently reported pain complaints, performance-based cognitive capabilities in patients with chronic fatigue syndrome (CFS) with and without comorbid fibromyalgia (FM) are significantly worse than those of healthy controls. In various chronic pain populations, cognitive impairments are known to be related to pain severity. However, to the best of our knowledge, the association between cognitive performance and experimental pain measurements has never been examined in CFS patients.

OBJECTIVES: This study aimed to examine the association between cognitive performance and self-reported as well as experimental pain measurements in CFS patients with and without FM.

STUDY DESIGN: Observational study.

SETTING: The present study took place at the Vrije Universiteit Brussel and the University of Antwerp.

METHODS: Forty-eight (18 CFS-only and 30 CFS+FM) patients and 30 healthy controls were studied. Participants first completed 3 performance-based cognitive tests designed to assess selective and sustained attention, cognitive inhibition, and working memory capacity. Seven days later, experimental pain measurements (pressure pain thresholds [PPT], temporal summation [TS], and conditioned pain modulation [CPM]) took place and participants were asked to fill out 3 questionnaires to assess self-reported pain, fatigue, and depressive symptoms.

RESULTS: In the CFS+FM group, the capacity of pain inhibition was significantly associated with cognitive inhibition. Self-reported pain was significantly associated with simple reaction time in CFS-only patients. The CFS+FM but not the CFS-only group showed a significantly lower PPT and enhanced TS compared with controls.

LIMITATIONS: The cross-sectional nature of this study does not allow for inferences of causation.

CONCLUSIONS: The results underline disease heterogeneity in CFS by indicating that a measure of endogenous pain inhibition might be a significant predictor of cognitive functioning in CFS patients with FM, while self-reported pain appears more appropriate to predict cognitive functioning in CFS patients without FM.

Source: Ickmans K, Meeus M, De Kooning M, Lambrecht L, Pattyn N, Nijs J. Associations Between Cognitive Performance and Pain in Chronic Fatigue Syndrome: Comorbidity with Fibromyalgia Does Matter. Pain Physician. 2015 Sep-Oct;18(5):E841-52. http://www.painphysicianjournal.com/current/pdf?article=MjQxOA%3D%3D&journal=91 (Full article as PDF file)

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract:

Milnacipran, a serotonin/norepinephrine reuptake inhibitor, has been approved by the US Food and Drug Administration for the treatment of fibromyalgia (FM). This report presents the results of a randomized, double-blind, placebo-controlled trial of milnacipran conducted to test the hypotheses that a) similar to patients with chronic fatigue syndrome, patients with FM have increased ventricular lactate levels at baseline; b) 8 weeks of treatment with milnacipran will lower ventricular lactate levels compared with baseline levels and with ventricular lactate levels after placebo; and c) treatment with milnacipran will improve attention and executive function in the Attention Network Test compared with placebo. In addition, we examined the results for potential associations between ventricular lactate and pain. Baseline ventricular lactate measured by proton magnetic resonance spectroscopic imaging was found to be higher in patients with FM than in healthy controls (F1,37 = 22.11, P < .0001, partial η(2) = .37). Milnacipran reduced pain in patients with FM relative to placebo but had no effect on cognitive processing.

At the end of the study, ventricular lactate levels in the milnacipran-treated group had decreased significantly compared with baseline and after placebo (F1,18 = 8.18, P = .01, partial η(2) = .31). A significantly larger proportion of patients treated with milnacipran showed decreases in both ventricular lactate and pain than those treated with placebo (P = .03). These results suggest that proton magnetic resonance spectroscopic imaging measurements of lactate may serve as a potential biomarker for a therapeutic response in FM and that milnacipran may act, at least in part, by targeting the brain response to glial activation and neuroinflammation.

PERSPECTIVE: Patients treated with milnacipran showed decreases in both pain and ventricular lactate levels compared with those treated with placebo, but, even after treatment, levels of ventricular lactate remained higher than in controls. The hypothesized mechanism for these decreases is via drug-induced reductions of a central inflammatory state.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01108731.

Source: Natelson BH, Vu D, Mao X, Weiduschat N, Togo F, Lange G, Blate M, Kang G, Coplan JD, Shungu DC. Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Trial. J Pain. 2015 Nov;16(11):1211-9. doi: 10.1016/j.jpain.2015.08.004. Epub 2015 Aug 31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630071/ (Full article)

Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) often complain of persistent fatigue even after conventional therapies such as pharmacotherapy, cognitive behavioral therapy, or graded exercise therapy. The aim of this study was to investigate in a randomized, controlled trial the feasibility and efficacy of isometric yoga in patients with CFS who are resistant to conventional treatments.

METHODS: This trial enrolled 30 patients with CFS who did not have satisfactory improvement after receiving conventional therapy for at least six months. They were randomly divided into two groups and were treated with either conventional pharmacotherapy (control group, n = 15) or conventional therapy together with isometric yoga practice that consisted of biweekly, 20-minute sessions with a yoga instructor and daily in-home sessions (yoga group, n = 15) for approximately two months. The short-term effect of isometric yoga on fatigue was assessed by administration of the Profile of Mood Status (POMS) questionnaire immediately before and after the final 20-minute session with the instructor. The long-term effect of isometric yoga on fatigue was assessed by administration of the Chalder’s Fatigue Scale (FS) questionnaire to both groups before and after the intervention. Adverse events and changes in subjective symptoms were recorded for subjects in the yoga group.

RESULTS: All subjects completed the intervention. The mean POMS fatigue score decreased significantly (from 21.9 ± 7.7 to 13.8 ± 6.7, P < 0.001) after a yoga session. The Chalder’s FS score decreased significantly (from 25.9 ± 6.1 to 19.2 ± 7.5, P = 0.002) in the yoga group, but not in the control group. In addition to the improvement of fatigue, two patients with CFS and fibromyalgia syndrome in the yoga group also reported pain relief. Furthermore, many subjects reported that their bodies became warmer and lighter after practicing isometric yoga. Although there were no serious adverse events in the yoga group, two patients complained of tiredness and one of dizziness after the first yoga session with the instructor.

CONCLUSIONS: Isometric yoga as an add-on therapy is both feasible and successful at relieving the fatigue and pain of a subset of therapy-resistant patients with CFS.

TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN CTR) UMIN000009646.

Source: Oka T, Tanahashi T, Chijiwa T, Lkhagvasuren B, Sudo N, Oka K. Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial. Biopsychosoc Med. 2014 Dec 11;8(1):27. doi: 10.1186/s13030-014-0027-8. ECollection 2014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269854/ (Full article)

The Process of Change in Pain During Cognitive-Behavior Therapy for Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Cognitive-behavior therapy (CBT) leads to a reduction of fatigue and pain in chronic fatigue syndrome. The processes underlying the reduction in pain have not been investigated. Recently, it was shown that increased self-efficacy, decreased focusing on symptoms, increased physical functioning, and a change in beliefs about activity contribute to the decrease in fatigue.

OBJECTIVES: The present study has 2 objectives: (1) to determine the relationship between the reduction of fatigue and pain during CBT; (2) test to what extent the model for change in fatigue is applicable to the reduction in pain.

MATERIALS AND METHODS: One hundred forty-two patients meeting United States centers for Disease Control and Prevention criteria for chronic fatigue syndrome, currently reporting pain, and starting CBT were included. A cross-lagged analysis was performed to study the causal direction of change between pain and fatigue. Pain and process variables were assessed before therapy, 3 times during CBT, and after therapy. Actual physical activity was also assessed. The model was tested with multiple regression analyses.

RESULTS: The direction of change between pain and fatigue could not be determined. An increase in physical functioning and decrease in focusing on symptoms explained 4% to 14% of the change in pain.

CONCLUSIONS: Pain and fatigue most probably decrease simultaneously during CBT. Pain reduction can partly be explained by a reduction of symptom focusing and increased physical functioning. Additional, yet unknown cognitive-behavioral factors also play a role in the reduction of pain.

Source: Bloot L, Heins MJ, Donders R, Bleijenberg G, Knoop H. The Process of Change in Pain During Cognitive-Behavior Therapy for Chronic Fatigue Syndrome. Clin J Pain. 2015 Oct;31(10):914-21. doi: 10.1097/AJP.0000000000000191. https://www.ncbi.nlm.nih.gov/pubmed/25503595

Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study

Abstract:

OBJECTIVES: Although pain is a significant symptom in chronic fatigue syndrome (CFS), pain is poorly understood in adolescents with CFS. The aim of this study was to explore pain distribution and prevalence, pain intensity and its functional interference in everyday life, as well as pressure pain thresholds (PPT) in adolescents with CFS and compare this with a control group of healthy adolescents (HC).

METHODS: This is a case-control, cross-sectional study on pain including 120 adolescents with CFS and 39 HCs, aged 12-18 years. We measured pain frequency, pain severity and pain interference using self-reporting questionnaires. PPT was measured using pressure algometry. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.

RESULTS: Adolescents with CFS had significantly lower PPTs compared with HCs (p<0.001). The Pain Severity Score and the Pain Interference Score were significantly higher in adolescents with CFS compared with HCs (p<0.001). Almost all adolescents with CFS experienced headache, abdominal pain and/or pain in muscles and joints. Moreover, in all sites, the pain intensity levels were significantly higher than in HCs (p<0.001).

CONCLUSIONS: We found a higher prevalence of severe pain among adolescents with CFS and lowered pain thresholds compared with HCs. The mechanisms, however, are still obscure. Large longitudinal population surveys are warranted measuring pain thresholds prior to the onset of CFS.

TRIAL REGISTRATION NUMBER: Clinical Trials, NCT01040429; The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL) http://www.clinicaltrials.gov.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Source: Winger A, Kvarstein G, Wyller VB, Sulheim D, Fagermoen E, Småstuen MC, Helseth S. Pain and pressure pain thresholds in adolescents with chronic fatigue syndrome and healthy controls: a cross-sectional study. BMJ Open. 2014 Oct 6;4(9):e005920. doi: 10.1136/bmjopen-2014-005920. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187660/ (Full article)

The effect of relaxation therapy on autonomic functioning, symptoms and daily functioning, in patients with chronic fatigue syndrome or fibromyalgia: a systematic review

Abstract:

OBJECTIVE: To establish the effects of relaxation therapy on autonomic function, pain, fatigue and daily functioning in patients with chronic fatigue syndrome or fibromyalgia.

METHOD: A systematic literature study was performed. Using specific keywords related to fibromyalgia or chronic fatigue syndrome and relaxation therapy, the electronic databases PubMed and Web of Science were searched. Included articles were assessed for their risk of bias and relevant information regarding relaxation was extracted. The review was conducted and reported according to the PRISMA-statement.

RESULTS: Thirteen randomized clinical trials of sufficient quality were included, resulting in a total of 650 fibromyalgia patients (11 studies) and 88 chronic fatigue syndrome patients (3 studies). None of the studies reported effects on autonomic function. Six studies reported the effect of guided imagery on pain and daily functioning in fibromyalgia. The acute effect of a single session of guided imagery was studied in two studies and seems beneficial for pain relief. For other relaxation techniques (eg. muscle relaxation, autogenic training) no conclusive evidence was found for the effect on pain and functioning in fibromyalgia patients comparison to multimodal treatment programs. For fatigue a multimodal approach seemed better than relaxation, as shown in the sole three studies on chronic fatigue syndrome patients.

CONCLUSION: There is moderate evidence for the acute effect of guided imagery on pain, although the content of the visualization is a matter of debate. Other relaxation formats and the effects on functionality and autonomic function require further study.

Source: Meeus M, Nijs J, Vanderheiden T, Baert I, Descheemaeker F, Struyf F. The effect of relaxation therapy on autonomic functioning, symptoms and daily functioning, in patients with chronic fatigue syndrome or fibromyalgia: a systematic review. Clin Rehabil. 2015 Mar;29(3):221-33. doi: 10.1177/0269215514542635. Epub 2014 Sep 8. https://www.ncbi.nlm.nih.gov/pubmed/25200878

A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation

Abstract:

Patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FMS) display multiple symptoms, such as chronic widespread pain, fatigue, sleep disturbance, and cognitive dysfunction. Abnormal pain sensation may be the most serious of these symptoms; however, its pathophysiology remains unknown.

To provide insights into the molecular basis underlying abnormal pain in CFS and FMS, we used a multiple continuous stress (CS) model in rats, which were housed in a cage with a low level of water (1.5 cm in depth). The von Frey and Randall-Seritto tests were used to evaluate pain levels.

Results showed that mechanical allodynia at plantar skin and mechanical hyperalgesia at the anterior tibialis (i.e., muscle pain) were induced by CS loading. Moreover, no signs of inflammation and injury incidents were observed in both the plantar skin and leg muscles. However, microglial accumulation and activation were observed in L4-L6 dorsal horn of CS rats. Quantification analysis revealed a higher accumulation of microglia in the medial part of Layers I-IV of the dorsal horn. To evaluate an implication of microglia in pain, minocycline was intrathecally administrated (via an osmotic pump). Minocycline significantly attenuated CS-induced mechanical hyperalgesia and allodynia.

These results indicated that activated microglia were involved in the development of abnormal pain in CS animals, suggesting that the pain observed in CFS and FMS patients may be partly caused by a mechanism in which microglial activation is involved.

Source: Yasui M, Yoshimura T, Takeuchi S, Tokizane K, Tsuda M, Inoue K, Kiyama H. A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation. Glia. 2014 Sep;62(9):1407-17. doi: 10.1002/glia.22687. Epub 2014 May 23. https://www.ncbi.nlm.nih.gov/pubmed/24852223

Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial

Abstract:

OBJECTIVE: Temporal summation (TS) of pain, conditioned pain modulation (CPM), and exercise-induced analgesia (EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia (CFS/FM), and patients with rheumatoid arthritis (RA), both under placebo and paracetamol condition.

METHODS: Fifty-three female volunteers – of which 19 patients with CFS/FM, 16 patients with RA, and 18 healthy controls – underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM.

RESULTS: Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo (P < 0.05). In patients with CFS/FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen.

CONCLUSION: This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/FM, these positive effects were only observed after paracetamol and results were inconsistent.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01154647.

Source: Meeus M, Hermans L, Ickmans K, Struyf F, Van Cauwenbergh D, Bronckaerts L, De Clerck LS, Moorken G, Hans G, Grosemans S, Nijs J. Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial. Pain Pract. 2015 Feb;15(2):98-106. doi: 10.1111/papr.12181. Epub 2014 Feb 17. https://www.ncbi.nlm.nih.gov/pubmed/24528544

Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial

Abstract:

BACKGROUND: Pain is a common symptom of chronic fatigue syndrome (CFS). We investigated the effects of the treatments used in the PACE trial [cognitive behavioural therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy (APT) and specialist medical care (SMC)] on pain in CFS.

METHOD: We compared pain outcomes including individual painful symptoms, taken from the CDC criteria for CFS and co-morbid fibromyalgia. We modelled outcomes adjusting for baseline variables with multiple linear regression.

RESULTS: Significantly less frequent muscle pain was reported by patients following treatment with CBT compared to SMC (mean difference = 0.38 unit change in frequency, p = 0.02), GET versus SMC (0.42, p = 0.01) and GET versus APT (0.37, p = 0.01). Significantly less joint pain was reported following CBT versus APT (0.35, p = 0.02) and GET versus APT (0.36, p = 0.02). Co-morbid fibromyalgia was less frequent following GET versus SMC (0.03, p = 0.03). The effect sizes of these differences varied between 0.25 and 0.31 for muscle pain and 0.24 and 0.26 for joint pain. Treatment effects on pain were independent of ‘change in fatigue’.

CONCLUSIONS: CBT and GET were more effective in reducing the frequency of both muscle and joint pain than APT and SMC. When compared to SMC, GET also reduced the frequency of co-morbid fibromyalgia; the size of this effect on pain was small.

Source: Bourke JH, Johnson AL, Sharpe M, Chalder T, White PD. Pain in chronic fatigue syndrome: response to rehabilitative treatments in the PACE trial. Psychol Med. 2014 May;44(7):1545-52. doi: 10.1017/S0033291713002201. Epub 2013 Aug 23. https://www.ncbi.nlm.nih.gov/pubmed/23967878