Gitte Handberg

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.

Health care costs, work productivity and activity impairment in non-malignant chronic pain patients

This study explores the costs of non-malignant chronic pain in patients awaiting treatment in a multidisciplinary pain clinic in a hospital setting. Health care costs due to chronic pain are particular high during the first year after pain onset, and remain high compared with health care costs before pain onset. The majority of chronic pain patients incur the costs of alternative treatments. Chronic pain causes production losses at work, as well as impairment of non-work activities.

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.

No morphine sparing effect of ketamine added to morphine for patient-controlled intravenous analgesia after uterine artery embolization.

Background: Pain following embolization of the uterine arteries (UAEs) is variable and may be very severe requiring large doses of parenteral opioids for relief. The present study tested the hypothesis that the addition of ketamine to IV patient‐controlled morphine reduces the amount of morphine required for pain‐control during the first 24 h after UAE embolization.

Suicide attempts in chronic pain patients. A register-based study

Abstract Background There are several studies about the relationship between depression and chronic non-malignant pain. These studies have shown that up to 50% of chronic pain patients are suffering from depression. It is, therefore, reasonable to expect that pain patients would also have an increased risk of suicidal behaviour. This problem is not well studied. Since 1990 the Centre for Suicide Research, Odense, Denmark has registered all suicide attempts in patients residing in the Region of Funen, Denmark. The Pain Clinic, Odense University Hospital receives patients with chronic pain from the entire Region of Southern Denmark. Purpose The purpose of the study has been: To investigate, whether patients treated in the Pain Clinic during the period from 1 January 2004 to 31 December 2009 had an increased risk of suicide attempts compared with the background population. Materials and methods The Register for Suicide Attempts (RSA) is a product of the WHO research programme WHO/EURO Multicentre Study on Para suicide. The RSA is a longitudinal person-based register. It contains information about people who have been in contact with the health care system in the County of Funen as a result of a suicide attempt. The Pain Clinic, Odense University Hospital receives patients with non-malignant chronic pain from the Region of Southern Denmark with 1,194,659 inhabitants. Data about age, sex, and time of treatment for patients treated in the Pain Clinic during the period were registered. Time and method of the suicide attempts were registered in the RSA. By registry linkages between the patient registers it was possible to calculate any excess risk of suicide attempts in chronic pain patients in the study period. We used a cohort design and calculated incidence rates (IR) and incidence rate ratios (IRRs) for suicide attempts, based on data from RSA. Poisson Regression analyses were used for calculation of IR and IRR for suicide attempts. Results In the study period from 1 January 2004 to 31 December 2009 1871 patients residing in the Region of Funen in Denmark were referred to The Pain Clinic. In the patient group 258 suicide attempts in 110 persons were registered. In all 6% of the patient group had attempted suicide. An increased risk of suicide attempts was found in the pain population as the incidence rate ratio (IRR) was 3.76 95% CI (3.22; 4.40). No statistical significant differences between men and women were found. Conclusion In a chronic non-malignant pain population, referred to a pain clinic, the risk of suicide attempts was increased. Implications It is important to be aware of risk factors for suicidal behaviour, i.e. pain history, depression, anxiety, abuse problems, and social problems when caring for patients with chronic pain. More knowledge and training of the staff caring for chronic pain patients are needed to decrease the risk of suicidal behaviour.

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.