Linda Hermans

The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?

Introduction: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are characterized by persistent pain and fatigue. It is hypothesized that reactive oxygen species (ROS), caused by oxidative and nitrosative stress, by inhibiting mitochondrial function can be involved in muscle pain and central sensitization as typically seen in these patients. Areas covered: The current evidence regarding oxidative and nitrosative stress and mitochondrial dysfunction in CFS and FM is presented in relation to chronic widespread pain. Mitochondrial dysfunction has been shown in leukocytes of CFS patients and in muscle cells of FM patients, which could explain the muscle pain. Additionally, if mitochondrial dysfunction is also present in central neural cells, this could result in lowered ATP pools in neural cells, leading to generalized hypersensitivity and chronic widespread pain. Expert opinion: Increased ROS in CFS and FM, resulting in impaired mitochondrial function and reduced ATP in muscle and neural cells, might lead to chronic widespread pain in these patients. Therefore, targeting increased ROS by antioxidants and targeting the mitochondrial biogenesis could offer a solution for the chronic pain in these patients. The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area.

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

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.

Inventory of Personal Factors Influencing Conditioned Pain Modulation in Healthy People: A Systematic Literature Review

Conditioned pain modulation (CPM) is believed to play an important role in the development and exacerbation of chronic pain, because dysfunction of CPM is associated with a shift in balance between pain facilitation and pain inhibition. In many patients with central sensitization, CPM is less efficacious. Besides that, efficacy of CPM is highly variable in healthy people. Consequently, it seems that several individual variables may influence CPM. A systematic review examining personal factors influencing CPM was conducted.

The influence of sprint interval training on body composition, physical and metabolic fitness in adolescents and young adults with intellectual disability: a randomized controlled trial:

Objective: In this study we evaluated the effect of sprint interval training on metabolic and physical fitness in adolescents and young adults with intellectual disabilities when compared with continuous aerobic training and no training (control). Methods: Fifty-four persons with intellectual disabilities (age: 17 (3.0), body mass index: 27.7 (3.7), intelligence quotient: 59 (8.6)) were matched based on age, gender and intelligence quotient between sprint interval training (n = 17), continuous aerobic training (n = 15) and control (n = 14). Sprint interval training was composed of three blocks of 10 minutes at ventilatory threshold (blocks 1 and 3: 10 sprint bouts of 15 seconds, followed by 45 seconds relative rest; block 2: continuous training) twice a week for 15 weeks. Continuous aerobic training was composed of three blocks of 10 minutes continuous training. After eight weeks, intensity was increased to 110% of ventilatory threshold. The control group did not participate in supervised exercise training. Before and after the training period, body composition, physical and metabolic fitness were evaluated. Results: Sprint interval training showed a significant positive evolution for waist circumference, fat%, systolic blood pressure, lipid profile, fasting insulin, homeostasis model assessment of insulin resistance, peak VO2, peak Watt, ventilatory threshold, 6-minute walk distance and muscle fatigue resistance when compared with no training (P < 0.01). The sprint interval training group demonstrated significant improvements for fat%, systolic blood pressure, low-density lipoprotein, fasting insulin, peak VO2 and peak power and ventilatory threshold (P < 0.01) when compared with continuous aerobic training. Conclusion: In this study we could observe that sprint interval training has stronger beneficial effects on body composition, physical fitness and metabolic fitness compared with control. Compared with continuous aerobic training, sprint interval training seems to result in better outcome.

Influence of Morphine and Naloxone on Pain Modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia, and Controls: A Double‐Blind, Randomized, Placebo‐Controlled, Cross‐Over Study

Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown.

Endogenous pain modulation in the Ehlers–Danlos syndrome, hypermobility type

Purpose: The Ehlers-Danlos Syndrome (EDS) is the most prevalent heritable connective tissue disorder. More than 90% of individuals are classified as having the hypermobility type (EDS-HT). Patients typically demonstrate generalized severe joint hypermobility, which is frequently associated with recurrent joint dislocations and premature osteoarthritis. Although pain is the number one complaint in EDS-HT, causing severe disability in daily life, the underlying pain mechanisms and the nature of pain are unknown. Therefore, this study aims to assess the nature of pain (nociceptive / neuropathic / dysfunctional pain) and the endogenous pain modulation in EDS-HT. Methods: Twenty-one patients with EDS-HT were compared with 20 healthy control subjects (CON), and 11 fibromyalgia patients (FM). The latter was included, because FM has been the subject of a lot of research regarding endogenous pain modulatory deficits, and because of the large symptomatic overlap with EDS-HT. All patients filled out a Margolis Pain Diagram, the Pain Detect Questionnaire (PDQ) and questionnaires regarding cognitive-emotional sensitization (Pain Catastrophizing Scale - PCS, Hospital Anxiety and Depression Scale - HADS, Tampa Kinesiophobia Scale - TSK, Pain Vigilance and Awareness Scale – PVAQ). After a thorough anamnesis regarding medical history, the somatosensory system was evaluated. Thermal quantitative sensory testing was performed on the right trapezius and left tibialis anterior to determine the sensory thresholds for cold and warmth, and the pain thresholds for cold and heath. Next, pressure pain thresholds were examined on the right trapezius and quadriceps. Further, endogenous pain modulation was assessed by evaluating wind-up (WU), conditioned pain modulation (CPM) and exercise induced analgesia (EIA). WU was assessed by applying 10 pressure stimuli (at the pressure pain threshold) on the trapezius and quadriceps and by evaluating the subsequent increase in VAS score. CPM was induced by immersing the left hand into a 46° water bath and evaluating the subsequent decrease in VAS score (for a pressure stimulus at the pressure pain threshold). EIA was assessed by comparing the pressure pain threshold before and after a submaximal bicycle test (Aerobic Power Index Test). Results: Regarding the nature of pain, the EDS-HT group showed characteristics of neuropathic pain, with 89.5% of patients being classified by the PDQ as having possible or probable neuropathic pain. In addition, the EDS-HT group also showed characteristics of dysfunctional pain. The Margolis pain diagram showed a more widespread pain in patients with EDS-HT (p<0.001). WU at the trapezius was significantly higher in patients with EDS-HT and FM compared to controls (p=0.046). EIA was significantly reduced at the quadriceps in EDS and FM (p=0.041). By contrast, CPM did not significantly differ between groups (p=0.903). Cognitive emotional sensitization was present in the EDS-HT group (significantly higher scores on the PCS, HADS and TSK compared to controls; p <0.01). Conclusion: Patients with EDS-HT suffer from nociceptive, as well as neuropathic and dysfunctional pain. The endogenous pain modulation is disrupted by a reduced pain inhibition, which is comparable to FM.