Exercise-induced Hypoalgesia Response Research Articles

Exercise-Induced Hypoalgesia Following Proprioceptive Neuromuscular Facilitation and Resistance Training Among Individuals With Shoulder Myofascial Pain: Randomized Controlled Trial.

Various exercises can attenuate pain perception in healthy individuals and may interact with the descending pain modulation in the central nervous system. However, the analgesic effects of exercise in patients with myofascial pain can be disrupted by the pathological changes during chronic pain conditions. Thus, the exercises targeted on the facilitation of the sensory-motor interaction may have a positive impact on the restoration of the descending pain modulation and the analgesia effects. This paper estimates the effect of proprioceptive neuromuscular facilitation (PNF) and resistance training on exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) among patients with myofascial pain syndrome. A total of 76 female patients with myofascial pain syndrome (aged 18-30 years), with the pain in the upper trapezius and a visual analog scale score of greater than 30/100 mm, were enrolled in the study. Participants were randomly assigned into 3 intervention groups, including isometric (n=18, 24%), isotonic (n=19, 25%), and PNF (n=20, 26%) exercises, as well as 1 control group (n=19, 25%) with no intervention. Pressure pain threshold and the CPM responses at the myofascial trigger point, arm, and leg sites were assessed before and after the exercise session. The effective EIH response was reflected in the improvement of pressure pain thresholds. There was an increase in pressure pain thresholds and CPM responses at trigger point (P<.001 and P<.001), arm (P<.001 and P<.001), and leg sites (P<.001 and P=.03) in participants who performed PNF and isotonic exercise, while the isometric exercise only increased pressure pain thresholds at leg sites (P=.03). Compared with the control group, both the isotonic (P=.02) and PNF (P<.001) groups showed greater EIH responses at the trigger points. In comparison to the control group, only the PNF exercise (P=.01) significantly improved pressure pain thresholds and CPM responses at arm and leg sites compared to the control group. PNF, isotonic, and isometric exercises could lead to local and global EIH effects. The improvement in CPM response following PNF and isotonic exercises suggested that the EIH mechanisms of different resistance exercises may be attributed to the enhancement of the endogenous pain modulation via the motor-sensory interaction from the additional eccentric and dynamic muscle contraction. Chinese Clinical Trial Registry ChiCtr202111090819166165; https://tinyurl.com/2ab93p7n.

Symptomatic but not Asymptomatic COVID-19 Impairs Conditioned Pain Modulation in Young Adults

Pain is a common symptom reported in COVID-19 patients. Impaired endogenous pain-modulatory mechanisms such as conditioned pain modulation (CPM), and exercise-induced hypoalgesia (EIH) have been found in chronic pain conditions but is often overlooked in acute conditions that evoke painful symptoms, such as COVID-19. The purpose was to compare pressure-pain sensitivity, CPM, and EIH function among individuals who previously had COVID-19, both symptomatically and asymptomatically, and a healthy control group. Pressure pain thresholds of 59 participants were assessed in the forearm and leg using a pressure algometer before and after 1) submersion of their dominant foot in cold water (2°C) for 1min; and 2) isometric knee extension performed to task-failure at 25% of their maximal contraction. The CPM response was attenuated in individuals who were infected with symptomatic COVID-19 (N = 26) compared to asymptomatic COVID-19 (N = 13) in arm (-1.0% ± 20.3 vs 33.3% ± 26.2; P < .001) and leg (12.8% ± 22.0 vs 33.8% ± 28.2; P = .014) and compared to controls (N = 20) in arm only (-1.0% ± 26.2 vs 23.4% ± 28.2; P = .004). The EIH response was not different between groups. CPM was impaired in individuals who had symptomatic COVID-19, which may have long-term implications on pain modulation. PerspectiveThis study reveals that CPM was impaired in individuals who had symptomatic COVID-19 during the first wave of COVID-19, pre vaccine. These findings present a preliminary motive to study the long-term implications of COVID-19 and its effects on pain modulation.

Body composition does not influence conditioned pain modulation and exercise-induced hyperalgesia in healthy males and females.

Obese individuals report a higher susceptibility to chronic pain. Females are more likely to have chronic pain and excess adipose tissue. Chronic pain is associated with dysfunctional pain-modulatory mechanisms. Body composition differences may be associated with pain modulation differences in males and females. The purpose of this study was to investigate body composition (lean vs fat mass) differences and pain-modulatory functioning in healthy males and females. Pressure pain thresholds (PPT) of 96 participants (47 M; 49F) were assessed in both arms and legs before and after a double-footed ice bath (2°C) for 1 min and an isometric knee extension, time to failure task. The difference between post- and pre-measures was defined as conditioned pain-modulatory (CPM) response (ice bath) and exercise-induced hypoalgesia (EIH) response. Whole-body and site-specific fat and lean tissue were assessed via the DXA scan. Sex differences were found in whole-body lean mass (61.5 ± 6.7kg vs 41.2 ± 5.4kg; p < 0.001) but not fat mass amount (17.2 ± 10.5kg vs 21.0 ± 9.7kg; p=0.068). No effect of sex was found between limb CPM (p=0.237) and limb EIH (p=0.512). When controlling for lean mass, there was no significant effect of sex on CPM (p=0.732) or EIH (p=0.474) response. Similar findings were found for fat mass. The lack of difference suggests that males and females have similar modulatory functioning. It appears that in healthy adults free from chronic pain, neither fat mass nor lean mass has an influence on endogenous pain-modulatory function. Men and women exhibited similar CPM and EIH despite marked differences in body composition. Our findings suggest whole-body and limb-specific lean tissue mass and fat mass do not influence CPM and EIH in adults without chronic pain.

ASSOCIATION OF CONDITIONED PAIN MODULATION WITH EXERCISE-INDUCED HYPOALGESIA IN KNEE OSTEOARTHRITIS

Purpose: Although exercise is recommended as a first-line intervention for people with chronic knee pain due to osteoarthritis (OA), a significant proportion of people do not experience improvement in pain and could even report increased pain after exercise. Exercise-induced hypoalgesia (EIH), i.e., a reduction in pain or pain sensitivity after exercise, has been consistently observed in healthy individuals. However, EIH response can be impaired in people with chronic pain, including those with knee OA.

Association of pain intensity and patterns with response to exercise in knee osteoarthritis

Purpose: While exercise is recommended as the first-line intervention for people with chronic knee pain due to osteoarthritis (OA), a significant proportion of individuals do not respond to exercise interventions and may even report more pain. A normal response to a bout of exercise is characterized by reductions in pain and pain threshold, a phenomenon known as exercise induced hypoalgesia (EIH). Some individuals with chronic pain show an impaired EIH response immediately after exercise which may contribute to non-response after exercise interventions.

Modulation of Exercise-Induced Hypoalgesia Following an Exercise Intervention in Healthy Subjects.

Exercise is recommended to promote and maintain health and as treatment for more than 25 diseases and pain conditions. Exercise-induced hypoalgesia (EIH), a measure of descending pain inhibitory control, has been found to be impaired in some chronic pain conditions, but it is currently unclear if EIH is modifiable. This study investigated whether a long-term exercise intervention could modulate EIH in healthy subjects. In 38 healthy subjects, EIH was assessed as change in pressure pain threshold (PPT) after a three-minute isometric wall squat within the first week and after approximately seven weeks of military training (MT). Further, temporal summation of pain (TSP) and Knee injury and Osteoarthritis Outcome Score (KOOS) were assessed. Physical performance capacity was assessed using the Endurance 20-m shuttle run fitness test (20MSR). Hypoalgesic (EIH > 0.0 kPa) and hyperalgesic (EIH ≤ 0.0 kPa) subgroups were defined based on baseline EIH. Change in EIH following MT was used as the primary outcome. Increased EIH (P = 0.008), PPT (P < 0.003), and 20MSR (P < 0.001) were found following MT, with no changes in TSP and KOOS (P > 0.05). Subjects with a hyperalgesic EIH response at baseline (26% of the participants) presented significantly improved EIH following MT (P = 0.010). Finally, an association between 20MRS change and EIH change was found (r = 0.369, P = 0.023). MT increased EIH, especially in subjects who demonstrated a hyperalgesic response at baseline. Improvement in physical performance capacity was associated with an improvement in EIH, indicating that improvement in physical performance capacity may improve central pain mechanisms.

Exercise-induced Hypoalgesia Differ At Sites Local And Remote To The Exercising Muscle Group

Dysfunction of endogenous pain-inhibitory function such as exercise-induced hypoalgesia (EIH) may predict development of chronic pain conditions. While EIH has been shown to occur in both the exercised muscle group and in remote unexercised muscle group, few studies have compared the magnitude of EIH in an exercised muscle and remote muscle groups in the same individuals following the same exercise bout. PURPOSE: The purpose of the study was to examine the EIH response at four different sites following a bout of single legged isometric exercise. METHODS: Pressure pain thresholds (PPT) of 102 participants (50 females; 52 males) were assessed bilaterally in the vastus lateralis (VL) and brachioradialis (BR) using a pressure algometer before and after isometric knee extension at 25% of maximal voluntary contraction held until task failure using their dominant leg. The percent difference between post and pre measures was defined the EIH response. RESULTS: PPT’s increased in the left BR (18.1% ± 24.7; p<0.001, d=0.275), right BR (14.4% ± 26.1; p<0.001, d=0.233), non-dominant VL (17.4% ± 24.0; p<0.001, d=0.318) and the dominant VL (34.5% ± 28.3; p<0.001, d=0.643). There were no differences between the left and right BR and the non-dominant VL with regards to the EIH response (p>0.05), however the exercised leg demonstrated a greater EIH response compared to the remote, unexercised limbs (p<0.001). CONCLUSION: EIH occurred in all sites. However the EIH response in the exercised leg was significantly more robust than the remote, unexercised sites. This findings suggests the magnitude of EIH is determined by both local and systemic factors and this should be taken into consideration when comparing EIH among studies.

No Sex Differences In Conditioned Pain Modulation Or Exercise-induced Hypoalgesia Following Lower Body Isometric Exercise

Women are more at risk than men for developing chronic pain conditions. Differences in endogenous pain-modulatory function could be a contributing factor. PURPOSE: The aim of this study was to compare conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH) responses between adult men and women. METHODS: In a cross-sectional, non-randomized study with two independent groups of college aged males (n = 52) and females (n = 45), pressure pain thresholds (PPT) were assessed bilaterally in the vastus lateralis (VL) and brachioradialis (BR) muscles using a pressure algometer prior to and immediately following a conditioning stimulus (placing their foot in an ice bath) and performing isometric knee extension exercise to failure at 25% of maximal strength. RESULTS: Men had higher baseline PPTs than females (LBR: 372 ± 217 vs. 303 ± 119; RBR : 396 ± 236 vs. 315 ± 143; NDVL: 552 ± 281 vs. 434 ± 157 DVL: 572 ± 253 vs. 454 ± 147; P < 0.01). PPTs increased significantly (P < 0.05) following the conditioning stimulus in both males and females (LBR: 387 ± 264 to 453 ± 318 kPa, and 315 ± 126 to 359 ± 145 kPa; RBR: 400 ± 225 to 450 ± 280 kPa; and 325 ± 135 to 372 ± 161 kPa; DVL; 579 ± 289 to 658 ± 349 kPa;, and 470 ± 200 to 541 ± 201 kPa; NDVL 542 ± 263 to 623 ± 326 kPa; and 433 ± 174 to 503 ± 185 kPa in the in the males and females, respectively) indicating a CPM response in all limbs tested. PPTs increased significantly (P < 0.05) following isometric knee extension exercise to a similar extent in both males and females in all limbs tested (LBR: 387 ± 177 to 466 ± 245 kPa; and 305 ± 140 to 353 ± 162 kPa; RBR: 409 ± 172 to 462 ± 228 kPa; and 312 ± 147 to 355 ± 173 kPa. DVL: 572 ± 253 to 763 ± 366 kPa; and 454 ± 147 to 611 ± 252 kPa; NDVL: 552 ± 281 to 633 ± 353 kPa and 434 ± 157 to 526 ± 210 kPa) There was no interaction between the group x testing site for either the CPM response (P = 0.314) or the EIH response (P = 0.242). CONCLUSIONS: Men had a higher resting pain threshold than women. However, men and women exhibited similar endogenous pain inhibitory function both locally and systemically following a conditioning stimulus and isometric lower body exercise.

Exercise-induced Hypoalgesia Is Impaired in Chronic Whiplash-associated Disorders (WAD) With Both Aerobic and Isometric Exercise.

Exercise-induced hypoalgesia (EIH) can be impaired in patients with chronic pain and may be dependent on exercise type. Factors predictive of EIH are not known. This study aimed to: (1) compare EIH in participants with chronic whiplash-associated disorders (WAD) to asymptomatic controls, (2) determine if EIH differs between aerobic and isometric exercise, (3) determine predictors of EIH. A pre-post study investigated the effect of single sessions of submaximal aerobic treadmill walking and isometric knee extension on EIH in 40 participants with chronic WAD and 30 controls. Pressure pain thresholds were measured at the hand, cervical spine, and tibialis anterior. Pain intensity, reported previous week physical activity, temporal summation, and conditioned pain modulation (CPM) were measured at baseline. Participants with WAD demonstrated impaired EIH. Although, the WAD participants demonstrated a partial EIH response (EIH induced at the hand during exercise), no EIH response was found immediately after exercise. There was no difference in EIH between exercise types. In the WAD group, moderate physical activity levels predicted EIH at the hand and high physical activity levels predicted impaired EIH at the neck. More efficient CPM predicted EIH at the hand and less efficient CPM predicted impaired EIH at the neck. These associations were found for isometric exercise only. Individuals with chronic WAD have impaired EIH with both aerobic and isometric exercise. Higher levels of physical activity and less efficient CPM may be associated with impaired EIH. This may have implications for exercise prescription in this patient group.

Power of Words: Influence of Preexercise Information on Hypoalgesia after Exercise—Randomized Controlled Trial

Exercise increases pressure pain thresholds (PPT) in pain-free individuals, known as exercise-induced hypoalgesia (EIH). Positive preexercise information can elicit higher EIH responses, but the effect of positive versus negative preexercise information on EIH is unknown. The primary aim of this randomized controlled trial was to compare EIH at the exercising thigh muscle after an isometric squat exercise between individuals receiving positive versus negative preexercise information about the effect of exercise on pain. Secondary aims were to compare EIH at nonexercising muscles between groups, and to investigate the relationship between participants' expectations and EIH. Eighty-three participants were randomly assigned to brief positive (n = 28), neutral (n = 28) or negative (n = 27) verbal information. The neutral information group was included in the study as a reference group. Pressure pain thresholds at the thigh and trapezius muscles were assessed before and after the intervention (i.e., preexercise information+squat exercise). Expectations of pain relief were assessed using a numerical rating scale (-10 [most negative] to 10 [most positive]). Change in quadriceps and trapezius PPT after the squat exercise showed a large difference between the positive and negative information groups (quadriceps, 102 kPa; 95% confidence interval, 55-150; effect size, 1.2; trapezius, 41 kPa; 95% confidence interval, 16-65; effect size:, 0.9). The positive information group had a 22% increase in quadriceps PPT whereas the negative information group had a 4% decrease. A positive correlation was found between expectations and increase in PPT. Negative preexercise information caused hyperalgesia after the wall squat exercise, whereas positive or neutral preexercise information caused hypoalgesia. Positive preexercise information did not change the magnitude of EIH compared with neutral information.

The effect of blood flow restriction exercise on exercise-induced hypoalgesia and endogenous opioid and endocannabinoid mechanisms of pain modulation.

This study aimed to investigate and compare the magnitude of exercise-induced hypoalgesia (EIH) with low-intensity blood flow restriction (BFR) resistance exercise (RE) at varying pressures to other intensities of resistance exercise and examine endogenous mechanisms of pain reduction. Twelve individuals performed four experimental trials involving unilateral leg press exercise in a randomized crossover design: low-load RE at 30% of one repetition maximum (1RM), high-load RE (70% 1RM), and BFR-RE (30% 1RM) at a low and high pressure. BFR pressure was prescribed relative to limb occlusion pressure at 40% and 80% for the low- and high-pressure trials. Pressure pain thresholds (PPT) were assessed before and 5 min and 24 h following exercise in exercising and nonexercising muscles. Venous blood samples were collected at the same timepoints to determine plasma concentrations of beta-endorphin and 2-arachidonoylglycerol. High-pressure BFR-RE increased PPTs in the exercising limb to a greater extent than all other trials. Comparable systemic EIH effects were observed with HLRE and both BFR-RE trials. PPTs in the exercising limb remained elevated above baseline at 24 h postexercise following both BFR-RE trials. Postexercise plasma beta-endorphin concentration was elevated during the BFR-RE trials. No changes to 2-arachidonoylglycerol concentration were observed. High pressure BFR-RE causes a greater EIH response in the exercising limb that persists for up to 24 h following exercise. The reduction in pain sensitivity with BFR-RE is partly driven by endogenous opioid production of beta-endorphin. BFR-RE should be investigated as a possible pain-modulation tool in individuals with acute and chronic pain.NEW & NOTEWORTHY High-pressure blood flow restriction (BFR) causes a greater hypoalgesia response in the exercising limb (48%) compared with light and heavy load resistance exercise (10-34%). Performing light load resistance exercise with BFR causes systemic hypoalgesia comparable with heavy load resistance exercise (10-18%). BFR resistance exercise prolonged the exercise-induced hypoalgesia response for 24 h in the exercising limb (15% and 24%, respectively). Activation of endogenous opioid production and a conditioned pain modulation effect partly mediate the relationship between exercise and hypoalgesia.

Pretreatment Exercise-induced Hypoalgesia is Associated With Change in Pain and Function After Standardized Exercise Therapy in Painful Knee Osteoarthritis.

Exercise-induced hypoalgesia (EIH), a measure of descending pain inhibitory control, has been found hyperalgesic in subgroups of painful knee osteoarthritis (KOA) patients. The effect of standardized exercise therapy (ET) on clinical pain intensity in KOA has been demonstrated. However, the prognostic value of EIH in KOA patients completing an ET program has not been investigated. This study investigated the prognostic value of EIH on pain relief following ET in KOA patients. In 24 painful KOA patients (Numerical Rating Scale, 0 to 10 ≥3), EIH was assessed as change in pressure pain threshold after 2-minute "lateral raises" before and after ET in this observational study. In addition, temporal summation of pain, clinical pain scores (Numerical Rating Scale, Knee injury and Osteoarthritis Outcome Score [KOOS], and PainDETECT Questionnaire) were assessed before and after ET. The KOOS-4 is defined by the KOOS subscale scores for Pain, Symptoms, Activities of Daily Living, and Quality of Life and was used as the primary outcome. Following ET, all clinical pain scores improved (P<0.01) but no changes in pressure pain threshold, temporal summation of pain, or EIH were found (P>0.05). Linear regression models identified pretreatment EIH (β=0.59, P<0.005) and PainDETECT Questionnaire (β=0.57, P<0.005) as independent factors for relative change in KOOS-4 after ET (adjusted R=46.8%). These preliminary and exploratory results suggest that patients with a high EIH response before a standardized ET program may be associated with a large improvement in pain after treatment. This measure may potentially help clinicians as a prognostic tool for outcome prediction following ET in KOA patients.

Walking increases pain tolerance in humans: an experimental cross-over study.

Exercise is commonly used as treatment for chronic pain with positive long-term effects on pain and pain-related disability. In pain-free subjects, hypoalgesia following an acute bout of exercise compared with a control condition has consistently been demonstrated also known as exercise-induced hypoalgesia (EIH). Walking exercise, a low intensity aerobic exercise, is frequently used in clinical practice as an easily applicable intervention for patients with chronic pain. Walking exercise is furthermore recommended as an effective treatment for patients with chronic musculoskeletal pain conditions to alleviate pain and reduce disability, however, the effect of walking on pain sensitivity is currently unknown. The aims of the present study were to investigate (1) the acute effect of walking on pain sensitivity, and (2) the relative (between-subjects) and absolute (within-subject) test-retest reliability of the hypoalgesic response across two sessions separated by 1 week. In this randomised experimental cross-over study including two identical sessions, 35 pain-free subjects performed a standardized 6 min walking test and a duration-matched quiet rest condition in a randomized and counterbalanced order in each session. Before and after both conditions, handheld pressure pain thresholds (PPTs) were assessed at the thigh and shoulder, and pressure pain thresholds (cPPT) and pain tolerance (cPTT) were assessed with computer-controlled cuff algometry at the lower leg. Change in the pain sensitivity measures were analysed with repeated-measures ANOVAs, and test-retest reliability with intraclass correlation coefficients (ICC) and agreements in classification of EIH responders/non-responders between the two sessions. All subjects completed the walking conditions in both session 1 and session 2. The perceived intensity of walking assessed with rating of perceived exertion (RPE) and walking distance did not differ significantly between session 1 (distance: 632.5 ± 75.2 meters, RPE: 10.9 ± 1.9) and session 2 (distance: 642.1 ± 80.2 meters, RPE: 11.0 ± 2.4) (p > 0.11). Moreover, RPE showed excellent relative reliability with an ICC value of 0.95 [95%CI: 0.90-0.97]. Walking increased pain tolerance (mean difference: 2.6 kPa [95%CI: 0.5-4.9 kPa; p = 0.02]), but not pain thresholds compared with rest in both sessions. Hypoalgesia after walking demonstrated fair to good relative reliability (ICC = 0.61), however the agreement in classification of EIH responders/non-responders (absolute reliability) across sessions was low and not significant (κ = 0.19, p = 0.30). Walking consistently increased pain tolerance but not pain thresholds compared with a duration-matched control condition with fair to good relative reliability between sessions. Based on classification of EIH responders/non-responders the absolute reliability between the two sessions was low indicating individual variance in the EIH response. Future studies should investigate the hypoalgesic effect of a walking exercise in a clinical pain population.

Relationship Among Site Specific Fat, Lean Mass, And Endogenous Pain Inhibitory Function

Overweight individuals experience greater functional and psychological complications of chronic pain. Dysfunction of endogenous pain-modulatory mechanisms such as conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH) have been found across a host of chronic pain conditions. PURPOSE: The purpose of the study was to assess endogenous pain inhibitory function and its relationship with whole body and site specific lean and fat mass. METHODS: PPT of 73 participants (38F; 35M) were assessed in the vastus lateralis (VL) and brachioradialis (BR) using a pressure algometer on both sides of the body before and after submersion of their feet in an ice bath (2°C) for 1min and an isometric knee extension, time to failure task based off of 25% of their maximal voluntary contraction. The difference between post and pre measures was defined CPM response (ice bath) and EIH response (exercise condition). Whole body and site specific fat and lean tissue were assessed via DXA scan, and muscle and fat thickness were assessed in the right (R) and left (L) VL and BR using ultrasound and skinfolds. RESULTS: Both CPM and EIH responses significantly increased PPTs for all of the four measured sites (p ≤ 0.001). BF% (r=0.256; p=0.029) and fat mass (r=.277; p=0.018) correlated with LBR CPM but not with site specific measures (p>0.05). RBR, RVL, and LVL CPM did not correlate with any measures of body composition (p>0.05). An inverse relationship was found between dominant VL EIH and whole body lean mass (r=-0.259; p=0.028), as well as limb specific lean mass (r=-0.262; p=0.026). No relationships were found between any of the body composition measures and non-dominant VL (p>0.05). CONCLUSION: It appears that in young, healthy adults, whole body and site specific fat mass does not influence endogenous pain-inhibitory function. However, having more lean tissue may have a negative effect on the EIH response. This may be due to larger muscle mass leading to a faster rate of fatigue, reducing exercise time which may have influenced the EIH response rather than muscle mass per se.

(378) Leg Dominance May Influence Exercise-Induced Hypoalgesia Response to Moderate Intensity Retrowalking: A Pilot Study

Retrowalking (walking backwards) is often used clinically to address movement impairment. Whether retrowalking at a moderate intensity is sufficient to produce exercise-induced hypoalgesia (EIH) is unknown. This pilot study explored EIH following retrowalking in twenty healthy young adults (21.6 ± 2.9 yrs, 10 men). Pressure pain thresholds (PPTs) were assessed at bilateral quadriceps and left index finger nailbed utilizing a computerized pressure algometer (Medoc AlgoMed) pre/post 20 minutes quiet rest (session 1) and pre/post 20 minutes of retrowalking at 45-55% heart rate reserve (session 2). Participants pressed the indicator button when the applied pressure first became painful. The average of three trials at each site was used for PPT and site order was randomized between sessions. A significant trial x site interaction was identified. Post hoc testing revealed no significant trial effects after quiet rest at any site. After retrowalking, only the right quadriceps showed an increase in PPT (417.8 ± 146.3 vs 380.5 ± 122.8 kPa). Although baseline PPTs were significantly lower in the right quadriceps than the left in session 1 (362.9 ± 107.2 vs 395.1 ± 127.9 kPa), this difference did not reach significance in session 2 (380.5 ± 122.8 vs 417.4 ± 174 kPa). In both sessions, PPT of the right quadriceps increased to match that of the left (Quiet Rest: 383.8 ± 117.9 vs 382.7 ± 148.6 kPa; Retrowalking: 417.8 ± 146.3 vs 418.9 ± 167.8 kPa). Of the twenty participants, 18 reported right leg dominance, 1 left, and 1 failed to report. Our pilot data suggests that pain sensitivity and EIH response to retrowalking may vary based upon leg dominance; therefore, unilateral assessment of EIH with bilateral working muscles could produce spurious outcomes. Further investigation into the potential role of leg dominance on pain reports before and after this novel exercise task is warranted. Retrowalking (walking backwards) is often used clinically to address movement impairment. Whether retrowalking at a moderate intensity is sufficient to produce exercise-induced hypoalgesia (EIH) is unknown. This pilot study explored EIH following retrowalking in twenty healthy young adults (21.6 ± 2.9 yrs, 10 men). Pressure pain thresholds (PPTs) were assessed at bilateral quadriceps and left index finger nailbed utilizing a computerized pressure algometer (Medoc AlgoMed) pre/post 20 minutes quiet rest (session 1) and pre/post 20 minutes of retrowalking at 45-55% heart rate reserve (session 2). Participants pressed the indicator button when the applied pressure first became painful. The average of three trials at each site was used for PPT and site order was randomized between sessions. A significant trial x site interaction was identified. Post hoc testing revealed no significant trial effects after quiet rest at any site. After retrowalking, only the right quadriceps showed an increase in PPT (417.8 ± 146.3 vs 380.5 ± 122.8 kPa). Although baseline PPTs were significantly lower in the right quadriceps than the left in session 1 (362.9 ± 107.2 vs 395.1 ± 127.9 kPa), this difference did not reach significance in session 2 (380.5 ± 122.8 vs 417.4 ± 174 kPa). In both sessions, PPT of the right quadriceps increased to match that of the left (Quiet Rest: 383.8 ± 117.9 vs 382.7 ± 148.6 kPa; Retrowalking: 417.8 ± 146.3 vs 418.9 ± 167.8 kPa). Of the twenty participants, 18 reported right leg dominance, 1 left, and 1 failed to report. Our pilot data suggests that pain sensitivity and EIH response to retrowalking may vary based upon leg dominance; therefore, unilateral assessment of EIH with bilateral working muscles could produce spurious outcomes. Further investigation into the potential role of leg dominance on pain reports before and after this novel exercise task is warranted.

Role of neurosteroid allopregnanolone on age-related differences in exercise-induced hypoalgesia in rats

The beneficial effects of physical activity for pain are denominated exercise-induced hypoalgesia (EIH). Here, we examined the age-related change and potential role of the neurosteroid allopregnanolone (ALLO) on EIH in rats. Adult and aged rats were randomly divided into one of three groups; non-exercise control, Low-exercise, and High-exercise. The animals in the Low- and High-exercise groups were subjected to a 10-minute treadmill workout at 40% and 80% maximum oxygen intake intensity, respectively. In the Low-exercise groups, a significant EIH response was observed in aged but not in adult rats. The pre-treatment with ALLO synthesis inhibitor finasteride, but not opioid-receptor antagonist naloxone, inhibited the Low-exercise induced EIH response in aged rats. Furthermore, the Low-exercise increased brain ALLO levels in aged animals compared with controls, which was correlated with the mechanical pain sensitivity. On the other hand, High-exercise could induce EIH response in both adult and aged animals, but it was more effective in adult rats. The pre-treatment with naloxone, but not finasteride, reduced the EIH observed after High-exercise in both adult and aged rats. Our findings demonstrated that effective EIH can be achieved even by mild-intensity exercise in aged animals via an increase of the brain ALLO levels.

Hypoalgesia after bicycling at lactate threshold is reliable between sessions.

Exercise decreases pain sensitivity known as exercise-induced hypoalgesia (EIH). However, the consistency of EIH after an acute exercise protocol based on subjective ratings of perceived exertion has been questioned. Objectives were to compare the effect on pressure pain thresholds (PPTs) after bicycling with work-rate at the lactate threshold compared with quiet rest, and investigate between-session reliability of EIH. Thirty-four healthy subjects completed three sessions with 7 days in-between. In session 1, the lactate threshold was determined via blood samples (finger-tip pinprick, > 2mmol/l increase from warm-up) during a graded bicycling task. In session 2 and 3, all subjects performed (1) 15min quiet-rest, and (2) 15min bicycling (work-rate corresponding to the lactate threshold) in the two identical sessions. PPTs at the quadriceps and trapezius muscles were assessed before and after both conditions. Reliability was assessed by intraclass correlations (ICCs). Bicycling increased quadriceps PPT compared with quiet-rest in both sessions [mean difference: 45kPa (95% CI 19-72 kPa), P = 0.002]; however, the increase in trapezius PPT was not significant after exercise. The EIH responses demonstrated fair between-session test-retest reliability (quadriceps: ICC = 0.45; trapezius: ICC = 0.57, P < 0.05), and agreement in EIH responders and non-responders between sessions was significant (quadriceps: κ = 0.46 and trapezius: κ = 0.43, P < 0.05). In conclusion, bicycling at the lactate threshold increased PPT at the exercising muscle with fair reliability of the local EIH response. The results have implications for future EIH studies in subjects with and without pain and for clinicians who design exercise programs for pain relief.

Exercise-Induced Hypoalgesia After Isometric Wall Squat Exercise: A Test-Retest Reliabilty Study.

Isometric exercises decrease pressure pain sensitivity in exercising and nonexercising muscles known as exercise-induced hypoalgesia (EIH). No studies have assessed the test-retest reliability of EIH after isometric exercise. This study investigated the EIH on pressure pain thresholds (PPTs) after an isometric wall squat exercise. The relative and absolute test-retest reliability of the PPT as a test stimulus and the EIH response in exercising and nonexercising muscles were calculated. In two identical sessions, PPTs of the thigh and shoulder were assessed before and after three minutes of quiet rest and three minutes of wall squat exercise, respectively, in 35 healthy subjects. The relative test-retest reliability of PPT and EIH was determined using analysis of variance models, Person's r, and intraclass correlations (ICCs). The absolute test-retest reliability of EIH was determined based on PPT standard error of measurements and Cohen's kappa for agreement between sessions. Squat increased PPTs of exercising and nonexercising muscles by 16.8% ± 16.9% and 6.7% ± 12.9%, respectively (P < 0.001), with no significant differences between sessions. PPTs within and between sessions showed moderately strong correlations (r ≥ 0.74) and excellent (ICC ≥ 0.84) within-session (rest) and between-session test-retest reliability. EIH responses of exercising and nonexercising muscles showed no systematic errors between sessions; however, the relative test-retest reliability was low (ICCs = 0.03-0.43), and agreement in EIH responders and nonresponders between sessions was not significant (κ < 0.13, P > 0.43). A wall squat exercise increased PPTs compared with quiet rest; however, the relative and absolute reliability of the EIH response was poor. Future research is warranted to investigate the reliability of EIH in clinical pain populations.

Systemic Exercise-Induced Hypoalgesia Following Isometric Exercise Reduces Conditioned Pain Modulation.

Physically active individuals show greater conditioned pain modulation (CPM) compared with less active individuals. Understanding the effects of acute exercise on CPM may allow for a more targeted use of exercise in the management of pain. This study investigated the effects of acute isometric exercise on CPM. In addition, the between-session and within-session reliability of CPM was investigated. Experimental, randomized crossover study. Laboratory at Marquette University. Thirty healthy adults (19.3±1.5 years, 15 males). Subjects underwent CPM testing before and after isometric exercise (knee extension, 30% maximum voluntary contraction for three minutes) and quiet rest in two separate experimental sessions. Pressure pain thresholds (PPTs) at the quadriceps and upper trapezius muscles were assessed before, during, and after ice water immersions. PPTs increased during ice water immersion (i.e., CPM), and quadriceps PPT increased after exercise (P < 0.05). CPM decreased similarly following exercise and quiet rest (P > 0.05). CPM within-session reliability was fair to good (intraclass correlation coefficient [ICC] = 0.43-0.70), and the between-session reliability was poor (ICC = 0.20-0.35). Due to the variability in the systemic exercise-induced hypoalgesia (EIH) response, participants were divided into systemic EIH responders (N = 9) and nonresponders (N = 21). EIH responders experienced attenuated CPM following exercise (P = 0.03), whereas the nonresponders showed no significant change (P > 0.05). Isometric exercise decreased CPM in individuals who reported systemic EIH, suggesting activation of shared mechanisms between CPM and systemic EIH responses. These results may improve the understanding of increased pain after exercise in patients with chronic pain and potentially attenuated CPM.

Exercise does not produce hypoalgesia when performed immediately after a painful stimulus.

Exercise-induced hypoalgesia (EIH) and conditioned pain modulation (CPM) are assumed to reflect descending pain inhibition. Potential interactions between EIH and CPM may be important in the therapy of chronic pain, as reduced CPM and increased pain after exercise are frequently observed. This study compared the EIH response after CPM was activated using a cold pressor task with the EIH response after a control condition. Thirty-one participants (age: 27.7±9.8; 15 female) completed two sessions: a cold pressor task (CPT) session, i.e. testing EIH with preceding CPM activation induced using a 2 min CPT at approximately 2°C, and a control session, i.e. testing EIH after a control condition (2 min of quiet rest). EIH was induced using a 15 min bicycling exercise at a target heart rate corresponding to 75% VO2 max. Repeated measures ANOVAs on pressure pain thresholds (PPTs) at the hand, back and leg were used to determine the effects of exercise after the cold pressor test and control condition. Furthermore, correlations between CPM and EIH, in the CPT session as well as control session, were calculated at each assessment site. A significant time x condition interaction (F(1, 30)=43.61, p<0.001, partial η2=0.59), with Bonferroni-corrected post-hoc t-tests showed that PPTs increased after exercise in the control session (p<0.001), but not in the CPT session (p=0.125). Furthermore, there was a small positive correlation of EIH in the control session and CPM at the hand (r=0.37, p=0.043). There was a moderate negative correlation of EIH in the CPT session and CPM at the hand (r=-0.50, p=0.004), and smaller negative correlations at the back (r=-0.37, p=0.036) and at the leg (r=-0.35, p=0.054). Attenuated EIH after the CPM activation in comparison to a control condition suggests that EIH and CPM may share underlying pain inhibitory mechanisms on a systemic level. This assumption is further supported by the finding of small to moderate significant correlations between EIH and CPM at the hand. The attenuated EIH response furthermore suggests that these mechanisms are exhaustible, i.e. that its effects decline after a certain amount of inhibition. In patients with chronic pain, assessing the current capacity of the descending pain inhibitory system - as indicated by the CPM response - may aid to make better predictions about how patients will respond to exercise with respect to acute pain reduction.