Henrik Bjarke Vaegter

Similarities between exercise-induced hypoalgesia and conditioned pain modulation in humans

Summary Cold pressor pain and exercise causes multisegmental increases in pressure pain thresholds. Exercise is dominated by local manifestations of hypoalgesia, whereas cold pressor pain results generally in remote hypoalgesia. ABSTRACT Pain inhibitory mechanisms are often assessed by paradigms of exercise‐induced hypoalgesia (EIH) and conditioned pain modulation (CPM). In this study it was hypothesized that the spatial and temporal manifestations of EIH and CPM were comparable. The participants were 80 healthy subjects (40 females), between 18 and 65 years of age in this randomized, repeated‐measures cross‐over trial that involved data collection on 2 different days. CPM was assessed by 2 different cold pressor tests (hand and foot). EIH was assessed by 2 intensities of aerobic bicycling exercises and 2 intensities of isometric muscle contraction exercises (arm and leg). Pressure pain thresholds (PPTs) were recorded before, during, after, and 15 minutes after conditioning/exercise at sites local to and remote from the extremity used for cold pressor stimulation and exercise. PPTs increased at local as well as at remote sites during both cold pressor tests and after all of the exercise conditions except low‐intensity bicycling. EIH after bicycling was higher in women than in men. CPM and the EIH responses after isometric exercises were comparable in men and women and were not affected by age. The EIH response was larger in the exercising body part compared with nonexercising body parts for all exercise conditions. High‐intensity exercise produced greater EIH responses than did low‐intensity exercise. The change in PPTs during cold pressor tests and the change in PPTs after exercises were not correlated. The CPM response was not dominated by local manifestations, and the effect was seen only during the stimulation, whereas exercise had larger local manifestations, and the effects were also found after exercise.

Assessment of musculoskeletal pain sensitivity and temporal summation by cuff pressure algometry: a reliability study

Abstract Chronic musculoskeletal pain is linked with sensitization, and standardized methods for assessment are needed. This study investigated (1) the test–retest reliability of computer-controlled cuff-pressure algometry (pain thresholds and temporal pain summation) on the arm and leg and (2) conditioned pain modulation (CPM) assessed by cuff algometry. The influences of age and gender were evaluated. On 2 different days, cuff pain threshold (cPPT), cuff pain tolerance (cPTT), and temporal summation of pain (TSP) by visual analog scale scores to 10 repeated cuff stimulations at cPTT intensity, as well as pressure pain threshold with handheld pressure algometry, were assessed in 136 healthy subjects. In one session, cuff pain sensitivity was also assessed before and after cold pressor–induced CPM. Good-to-excellent intraclass correlations (0.60-0.90) were demonstrated for manual and cuff algometry, and no systematic bias between sessions was found for cPPT, cPTT, and TSP on the leg and for cPTT and TSP on the arm. Cuff pressure pain threshold and cPTT were higher in men compared with women (P < 0.05). Middle-aged subjects had higher pressure pain threshold, but lower cPPT and cPTT, compared with younger subjects (P < 0.05). Temporal summation of pain was increased in women compared with men (P < 0.05). Cuff algometry was sensitive to CPM demonstrated as increased cPPT and cPTT and reduced TSP (P < 0.05). Reliability and sensitivity of computer-controlled cuff algometry for pain assessment is comparable with manual pressure algometry and constitutes a user-independent method for assessment of pain. Difference in age-related pain sensitivity between manual and cuff algometry should be further investigated.

Hypoalgesia After Exercise and the Cold Pressor Test is Reduced in Chronic Musculoskeletal Pain Patients With High Pain Sensitivity.

Objectives:In chronic pain patients, impaired conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH) have been reported. No studies have compared CPM and EIH in chronic musculoskeletal pain patients with high pain sensitivity (HPS) and low pain sensitivity (LPS). Materials and Methods:On 2 days, manual pressure pain thresholds (PPTs) were recorded at the legs, arm, and shoulder in 61 chronic pain patients and they performed the cold pressor test, 2 exercise conditions (bicycling and isometric contraction), and a control condition in a randomized and counterbalanced order. PPTs, pain tolerance, pain tolerance limit, and temporal summation of pain were assessed with cuff algometry before and after the tests. On the basis of a median split of the average PPTs for women and men, respectively, low (LPS; N=30) and high (HPS; N=31) pain-sensitivity groups were created. Results:At baseline, cuff PPT and pain tolerance were decreased and temporal summation of pain was increased in the HPS group (P<0.02). Cuff PPT increased and pain tolerance limit decreased after the cold pressor test and exercises in LPS (P<0.001). Temporal summation of pain was increased after bicycling in HPS (P<0.005). Pain tolerance increased after the cold pressor test and exercise in both groups (P<0.001). Discussion:CPM and EIH were partly impaired in chronic pain patients with high versus less pain sensitivity, suggesting that the CPM and EIH responses depend on the degree of pain sensitivity. This has clinical implications as clinicians should evaluate pain sensitivity when considering treatment options utilizing the descending modulatory pain control.

Isometric exercises reduce temporal summation of pressure pain in humans

Aerobic and isometric exercises are known to decrease pain sensitivity. The effect of different types of exercise on central mechanisms such as temporal summation of pain (TSP) is less clear. This study hypothesized that both aerobic and isometric exercises would increase pressure pain tolerance (PTT) and reduce TSP with greater effects after higher‐intensity exercises.

Aerobic exercise and cold pressor test induce hypoalgesia in active and inactive men and women

BACKGROUND Physical inactivity is a risk factor for chronic pain. Several mechanisms play a role in pain chronification including impairment of pain inhibition. OBJECTIVE This study compared the efficiency of pain inhibitory systems between physical active and inactive healthy subjects. It was hypothesized that active subjects had more efficient pain inhibition compared with inactive subjects. DESIGN A randomized, crossover study with 2 days of data collection. METHODS Fifty-six (28 females) subjects participated in this study. Subjects were subgrouped into active (n = 30) and inactive (n = 26). Conditioned pain modulation (CPM) was assessed by cold pressor testing. Exercise-induced hypoalgesia (EIH) was assessed after 15 minutes bicycling at a heart rate corresponding to 75% VO2max. A control session of 15 minutes quiet rest was also included. Pressure pain thresholds (PPTs) were recorded at the dominant arm and leg before, immediately after, and 15 minutes after conditioning and exercise as well as before and after rest. PPTs were also recorded during conditioning. RESULTS At baseline, PPTs in inactive men were increased compared with inactive women (P < 0.003). During cold pressor test and after exercise, PPTs increased to the same degree in active and inactive subjects, and the CPM and EIH responses were correlated (P < 0.05). The CPM response immediately after cold pressor test was maintained in women but not in men. CONCLUSIONS Cold pressor stimulation and aerobic exercise caused comparable multisegmental increases in PPT in active and inactive men and women. The CPM and EIH responses were correlated, but they have different temporal manifestation of hypoalgesia.

Pain modulatory phenotypes differentiate subgroups with different clinical and experimental pain sensitivity

Abstract Pain biomarkers are warranted for individualized pain management. Based on different pain modulatory phenotypes, the objectives of this study were to explore the existence of subgroups within patients with nonmalignant chronic pain and to investigate differences in clinical pain and pain hypersensitivity between subgroups. Cuff algometry was performed on lower legs in 400 patients with chronic pain to assess pressure pain threshold, pressure pain tolerance, temporal summation of pain (TSP: increase in pain scores to 10 repeated stimulations), and conditioned pain modulation (CPM: increase in cuff pressure pain threshold during cuff pain conditioning on the contralateral leg). Heat detection and heat pain thresholds at clinical painful and nonpainful body areas were assessed. Based on TSP and CPM, 4 distinct groups were formed: group 1 (n = 85) had impaired CPM and facilitated TSP; group 2 (n = 148) had impaired CPM and normal TSP; group 3 (n = 45) had normal CPM and facilitated TSP; and group 4 (n = 122) had normal CPM and normal TSP. Group 1 showed more pain regions than the other 3 groups (P < 0.001), indicating that impaired CPM and facilitated TSP play an important role in widespread pain. Groups 1 and 2 compared with group 4 had lower heat pain threshold at nonpainful areas and lower cuff pressure pain tolerance (P < 0.02), indicating that CPM plays a role for widespread hyperalgesia. Moreover, group 1 demonstrated higher clinical pain scores than group 4 (P < 0.05). Although not different between subgroups, patients were profiled on demographics, disability, pain catastrophizing, and fear of movement. Future research should investigate interventions tailored towards these subgroups.

Prognostic factors for disability and sick leave in patients with subacute non-malignant pain: a systematic review of cohort studies

Objective This systematic review aims to identify generic prognostic factors for disability and sick leave in subacute pain patients. Setting General practice and other primary care facilities. Participants Adults (>18 years) with a subacute (≤3-month) non-malignant pain condition. Eligibility criteria were cohort studies investigating the prediction of disability or long-term sick leave in adults with a subacute pain condition in a primary care setting. 19 studies were included, referring to a total of 6266 patients suffering from pain in the head, neck, back and shoulders. Primary and secondary outcome measures The primary outcome was long-term disability (>3 months) due to a pain condition. The secondary outcome was sick leave, defined as ‘absence from work’ or ‘return-to-work’. Results PubMed, EMBASE, CINAHL and PEDro databases were searched from 16 January 2003 to 16 January 2014. The quality of evidence was presented according to the GRADE WG recommendations. Several factors were found to be associated with disability at follow-up for at least two different pain symptoms. However, owing to insufficient studies, no generic risk factors for sick leave were identified. Conclusions Multiple site pain, high pain severity, older age, baseline disability and longer pain duration were identified as potential prognostic factors for disability across pain sites. There was limited evidence that anxiety and depression were associated with disability in patients with subacute pain, indicating that these factors may not play as large a role as expected in developing disability due to a pain condition. Quality of evidence was moderate, low or very low, implying that confidence in the results is limited. Large prospective prognostic factor studies are needed with sufficient study populations and transparent reporting of all factors examined. Trial registration number CRD42014008914.

Prevalence of Neuropathic Pain According to the IASP Grading System in Patients with Chronic Non-Malignant Pain

OBJECTIVE The primary objective was to determine the prevalence of neuropathic pain according to the new International Association for the Study of Pain (IASP) grading system. The secondary objective was to compare the system classification of neuropathic pain with the classification of neuropathic pain according to a patient-administered screening questionnaire. SETTING A Multidisciplinary Pain Center. SUBJECTS One hundred twenty patients with a variety of chronic pain conditions referred to a multidisciplinary pain center. METHODS Consecutively referred patients filled out the PainDETECT Questionnaire before the first consultation. During the first consultation, patients had pain history taken and bedside examination performed by a pain specialist. Patients were classified according to the score on the PainDETECT Questionnaire and graded according to the IASP grading system about the certainty of neuropathic pain. RESULTS According to the IASP grading system, 22 patients (18.3%) classified as probable or definite neuropathic pain and 90 patients (75%) as unlikely neuropathic pain. According to the PainDETECT Questionnaire, 55 patients (45%) were classified as likely neuropathic pain and 13 patients (10.8%) as unlikely neuropathic pain. Eleven patients (20%) who were classified as neuropathic pain according to PainDETECT were also classified as probable or definite neuropathic pain by the new IASP grading system. CONCLUSIONS According to the new IASP grading system, less than 20% of the patients referred to a multidisciplinary pain center fulfilled the criteria for neuropathic pain. The classification of neuropathic pain with the IASP system varies from the classification of neuropathic pain with the use of a self-administered screening questionnaire.

Preoperative hypoalgesia after cold pressor test and aerobic exercise is associated with pain relief six months after total knee replacement

Objectives: Chronic pain after total knee replacement (TKR) is not uncommon. Preoperative impaired conditioning pain modulation (CPM) has been used to predict chronic postoperative pain. Interestingly, exercises reduce pain sensitivity in patients with knee osteoarthritis (KOA). This pilot study investigated the association between exercise-induced hypoalgesia (EIH) and CPM on post-TKR pain relief. Methods: Before and 6 months post-TKR, 14 patients with chronic KOA performed the cold pressor test on the nonaffected leg and 2 exercise conditions (bicycling and isometric knee extension), randomized and counterbalanced. Before and during the cold pressor test and after exercises test stimuli were applied to extract the pain sensitivity difference: computer-controlled cuff inflation on the affected lower leg until the participants detected the cuff pain threshold (cPPT) and subsequently the cuff pain tolerance (cPTT) and manual pressure pain thresholds (PPTs) at the legs, arm, and shoulder. Clinical pain intensity (numerical rating scale [NRS]) and psychological distress (questionnaires) were assessed. Results: Clinical pain intensity, psychological distress, cPPT, and PPT at the affected leg improved post-TKR compared with pre-TKR (P<0.05). Preoperatively, the CPM and bicycling EIH assessed by the increase in cPTT correlated with reduction in NRS pain scores post-TKR (P<0.05). Improved CPM and EIH responses after TKR were significantly correlated with reduction in NRS pain scores post-TKR (P<0.05). Discussion: In KOA patients, hypoalgesia after cold pressor stimulation and aerobic exercise assessed preoperatively by cuff algometry was associated with pain relief 6 months after TKR. EIH as a novel preoperative screening tool should be further investigated in larger studies.

Acetaminophen for Chronic Pain: A Systematic Review on Efficacy

Acetaminophen (paracetamol) is the most commonly used analgesic worldwide and recommended as first-line treatment in all pain conditions by WHO. We performed a systematic literature review to evaluate the efficacy of acetaminophen when used for chronic pain conditions. Applying three broad search strategies for acetaminophen use in chronic pain in both Embase and PubMed, 1551 hits were obtained. After cross-reference searches of both trials and 38 reviews, seven studies comparing acetaminophen in continuous dosing regimens of more than 2 weeks with placebo were included. The review was conducted according to the PRISMA guidelines. All studies were conducted in patients with hip- or knee osteoarthritis and six of seven studies had observation periods of less than 3 months. All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended.