Comparable Conditioned Pain Modulation and Painful-Exercise-Induced Hypoalgesia in Healthy Young Adults: A Randomized Crossover Trial.

Conditioned pain modulation and exercise-induced hypoalgesia reflect inhibitory pain controls emanating from the brain. The aim of this study was to compare the extent of pain inhibition from exercise-induced hypoalgesia (isometric wall squat), conditioned pain modulation (cold-water immersion), and their combination (wall squat followed by cold water in fixed order) in healthy pain-free adults. Sixty-one participants (median age 21 years) completed 3 sessions (wall-squat, cold-water, and combined) in random order. Sessions were separated by at least a week. In each session, pressure-pain thresholds, single-pinprick-pain ratings, and pinprick-temporal summation of pain (the fifth minus the first) were obtained at quadriceps, forearms, and forehead, before and after wall squat and/or cold water. Each intervention inhibited pain to pressure (partial η2 = .26) and single pinprick (partial η2 = .16) to a similar extent; however, pressure-pain inhibition was negligible in the forehead. After adjusting for age and sex, single-pinprick-pain inhibition in the forehead induced by wall squat was associated with that induced by cold water (adjusted R2 = .15; P = .007), and stronger pain inhibition was predicted by a higher thigh-pain rating to wall squat (adjusted R2 = .10; P = .027). Neither intervention affected pinprick-temporal summation of pain. Together, the findings suggest that pain-inhibitory effects of exercise-induced hypoalgesia and conditioned pain modulation may overlap when exercise is at least moderately painful (6/10 intensity). Pressure pain in body regions remote from the exercised or conditioned sites may be weakly modulated. PERSPECTIVE: The current findings suggest that pain-inhibitory effects induced by painful wall squat and by cold-water immersion may overlap. The magnitude of pain inhibition in the forehead remote from the exercised thigh or the conditioned foot appears smaller, which could be examined further in future research.

Muscle activity and hypoalgesia in blood flow restricted versus unrestricted effort-matched resistance exercise in healthy adults.

This study assessed muscle activity (root mean square, RMS, and median frequency, MDF) to evaluate the acute response to blood flow restriction (BFR) resistance exercise (RE) and conventional moderate intensity (MI) RE. We also performed exploratory analyses of differences based on sex and exercise-induced hypoalgesia (EIH). Fourteen asymptomatic individuals performed four sets of unilateral leg press with their dominant leg to volitional fatigue under two exercise conditions: BFR RE and MI RE. Dominant side rectus femoris (RF) and vastus lateralis (VL) muscle activity were measured using surface electromyography (sEMG) through exercise. RMS and MDF were calculated and compared between conditions and timepoints using a linear mixed model. Pressure pain thresholds (PPT) were tested before and immediately after exercise and used to quantify EIH. Participants were then divided into EIH responders and nonresponders, and the differences on RMS and MDF were compared between the two groups using Hedges' g. RMS significantly increased over time (RF: p = 0.0039; VL: p = 0.001) but not between conditions (RF: p = 0.4; VL: p = 0.67). MDF decreased over time (RF: p = 0.042; VL: p < 0.001) but not between conditions (RF: p = 0.74; VL: p = 0.77). Consistently lower muscle activation was found in females compared with males (BRF, RF: g = 0.63; VL, g = 0.5. MI, RF: g = 0.72; VL: g = 1.56), with more heterogeneous findings in MDF changes. For BFR, EIH responders showed greater RMS changes (Δ RMS) (RF: g = 0.90; VL: g = 1.21) but similar MDF changes (Δ MDF) (RF: g = 0.45; VL: g = 0.28) compared to nonresponders. For MI, EIH responders demonstrated greater increase on Δ RMS (g = 0.61) and decrease on Δ MDF (g = 0.68) in RF but similar changes in VL (Δ RMS: g = 0.40; Δ MDF: g = 0.39). These results indicate that when exercising to fatigue, no statistically significant difference was observed between BFR RE and conventional MI RE in Δ RMS and Δ MDF. Lower muscle activity was noticed in females. While exercising to volitional fatigue, muscle activity may contribute to EIH.

The effect of resistance exercise on multimodal pain thresholds in local and systemic muscle sites.

Dynamic resistance exercise may produce reductions in pain locally at the exercising muscle and systemically at non-exercising sites. However, limited research has examined these changes with multiple noxious stimuli. This study examined changes in heat pain threshold (HPT) and pressure pain threshold (PPT) on different musculature after an upper and lower body exercise to compare local and systemic effects. A crossover design with 28 participants (mean age: 21 ± 4 years, 21 female) completed three sessions. Visit one included baseline quantitative sensory testing and 5-repetition maximum (RM) testing for upper (shoulder press) and lower (leg extension) body. In subsequent sessions, participants performed upper or lower body exercises using an estimated 75% 1-RM with pre/post assessment of HPT and PPT at three sites: deltoid, quadriceps, and low back. A significant three-way interaction was observed for HPT (F (1.71, 3.80) = 2.19, p = 0.036, η2p = 0.12) with significant increases in HPT over the quadriceps (p = 0.043) after leg extension and over the deltoid (p = 0.02) after shoulder press. Significant systemic changes were not observed for HPT or PPT. Local but not systemic effects were demonstrated after an acute bout of exercise. Peripheral pain sensitivity may be more responsive to heat stimuli after resistance exercise.

Hypoalgesia after aerobic exercise in healthy subjects: A systematic review and meta-analysis.

Exercise-Induced Hypoalgesia (EIH) refers to an acute reduced pain perception after exercise. This systematic review and meta-analysis investigated the effect of a single aerobic exercise session on local and remote EIH in healthy individuals, examining the role of exercise duration, intensity, and modality. Pressure pain thresholds (PPT) are used as the main measure, applying the Cochrane risk of bias tool and GRADE approach for certainty of evidence assessment. Mean differences (MD; Newton/cm²) for EIH effects were analysed. Thirteen studies with 23 exercises and 14 control interventions are included (498 participants). Most studies used bicycling, with only two including running/walking and one including rowing. EIH occurred both locally (MD = 3.1) and remotely (MD = 1.8), with high-intensity exercise having the largest effect (local: MD = 7.5; remote: MD = 3.0) followed by moderate intensity (local: MD = 3.1; remote: MD = 3.0). Low-intensity exercise had minimal impact. Neither long nor short exercise duration induced EIH. Bicycling was found to be effective in eliciting EIH, in contrast to the limited research observed in other modalities. The overall evidence quality was moderate with many studies showing unclear risk biases.

Reliability and measurement error of exercise-induced hypoalgesia in pain-free adults and adults with musculoskeletal pain: A systematic review.

OBJECTIVES: We systematically reviewed the reliability and measurement error of exercise-induced hypoalgesia (EIH) in pain-free adults and in adults with musculoskeletal (MSK) pain. METHODS: We searched EMBASE, PUBMED, SCOPUS, CINAHL, and PSYCINFO from inception to November 2021 (updated in February 2024). In addition, manual searches of the grey literature were conducted in March 2022, September 2023, and February 2024. The inclusion criteria were as follows: adults - pain-free and with MSK pain - a single bout of exercise (any type) combined with experimental pre-post pain tests, and assessment of the reliability and/or measurement error of EIH. Two independent reviewers selected the studies, assessed their Risk of Bias (RoB) with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) RoB tool, and graded the individual results (COSMIN modified Grading of Recommendations Assessment, Development, and Evaluation). RESULTS: We included five studies involving pain-free individuals (n = 168), which were deemed to have an overall "doubtful" RoB. No study including adults with MSK pain was found. The following ranges of parameters of reliability and measurement error of EIH were reported: intraclass correlation coefficients: 0-0.61; kappa: 0.01-0.46; standard error of measurement: 30.1-105 kPa and 10.4-21%; smallest detectable changes: 83.54-291.1 kPa and 28.83-58.21%. CONCLUSIONS: We concluded, with a very low level of certainty, that the reliability and measurement error of EIH is, in pain-free adults, respectively, "insufficient" and "indeterminate." Future studies should focus on people with MSK pain and could consider using tailored exercises, other test modalities than pressure pain threshold, rater/assessor blinding, and strict control of the sources of variations (e.g., participants' expectations).

Exercise-induced hypoalgesia in chronic neck pain: A narrative review.

Chronic neck pain (CNP) is a worldwide health problem with several risk factors. One of the most widely used treatments for managing this condition is therapeutic exercise, which could generate a response called exercise-induced hypoalgesia (EIH). There is no consensus on the best exercise modality to induce hypoalgesia. Therefore, this review aims to analyze and synthesize the state-of-the-art about the hypoalgesic effect of exercise in subjects with CNP. We included articles on EIH and CNP in patients older than 18 years, with pain for more than three months, where the EIH response was measured. Articles that studied CNP associated with comorbidities or measured the response to treatments other than exercise were excluded. The studies reviewed reported variable results. Exercise in healthy subjects has been shown to reduce indicators of pain sensitivity; however, in people with chronic pain, the response is variable. Some investigations reported adverse effects with increased pain intensity and decreased pain sensitivity, others found no clinical response, and some even reported EIH with decreased pain and increased sensitivity. EIH is an identifiable, stimulable, and helpful therapeutic response in people with pain. More research is still needed on subjects with CNP to clarify the protocols and therapeutic variables that facilitate the EIH phenomenon. In addition, it is necessary to deepen the knowledge of the intrinsic and extrinsic factors that influence EIH in people with CNP.

Exercise-Induced Hypoalgesia in Patients with Chronic Whiplash-Associated Disorders: Differences between Subgroups Based on the Central Sensitization Inventory.

BACKGROUND: Physical exercise is an important element in the rehabilitation of chronic whiplash-associated disorders, with the physiological process underlying pain reduction called exercise-induced hypoalgesia. In chronic whiplash-associated disorders, exercise-induced hypoalgesia appears impaired, and the research suggests a relationship with symptoms of dysfunctional nociceptive processing, such as central sensitization. This study improves our understanding of exercise-induced hypoalgesia in chronic whiplash-associated disorders by examining the differences between the extent of exercise-induced hypoalgesia in subgroups based on scores on the central sensitization inventory (CSI). METHODS: Data were collected from 135 participants with chronic whiplash-associated disorders who completed a set of questionnaires. Pain pressure thresholds and temporal summations were assessed before and after a submaximal aerobic bicycle exercise test. RESULTS: We observed no interaction effect between exercise-induced hypoalgesia and the CSI scores for both pain pressure threshold and temporal summation. No overall statistical effect was measured in the analysis of the effect of time. The pain pressure threshold significantly related to the CSI. The temporal summation showed no correlation. CONCLUSIONS: During this study, we did not find evidence for a difference in the presence of exercise-induced hypoalgesia when the subgroups were created based on the central sensitization cluster calculator. Limited evidence was found for the influence of CSI scores on the delta pain pressure threshold.

Pain Science in Practice (Part 6): How Does Descending Modulation of Pain Work?

SYNOPSIS: To understand the neuroscience of pain relief, one must know about the descending pain modulatory system. Neuronal pathways that originate in the brainstem and project to the spinal cord to modulate spinal neuronal activity provide a well-documented perspective on the mechanisms of analgesia that underpin pharmacological and nonpharmacological treatment options for people with musculoskeletal pain. Peripheral stimuli or signals from the cortex and subcortical regions of the brain can trigger the descending pain modulatory system (DPMS). The system helps explain how counter-stimulation techniques (eg, acupuncture and manual therapy), the patients' expectations and beliefs, and social or contextual factors could influence how people experience pain. J Orthop Sports Phys Ther 2024;54(2):1-4. doi:10.2519/jospt.2024.12112.

Potential Local Mechanisms for Exercise-Induced Hypoalgesia in Response to Blood Flow Restriction Training.

Overall, there is a great need within sports medicine to ensure that athletes can return from injury in an efficient, yet thorough manner. It is crucial to not avoid necessary difficulties in this process but also to ensure time-efficient rehabilitation. One of the more promising techniques to achieve timely recovery is blood flow restriction (BFR) training. BFR training is a growing and novel development that could be a vital tool to lighten the burden of recovery from injury in athletes. BFR utilizes a pneumatic tourniquet to limit blood flow in specific areas of the body. The use of BFR has been shown to potentially enhance the analgesic effects of exercise-induced hypoalgesia (EIH). By limiting pain, athletes will be less burdened by mobility and loading exercises required for them to effectively return to play. In a field where time away from sports can have massive implications, the need for tools to assist in the acceleration of the rehabilitation process is vital. Much of the work that has already been done in the field has been able to exploit the benefits of EIH and further enhance the body's capabilities through BFR. Studies have compared EIH at low- and high-intensity settings utilizing BFR with both resistance and aerobic exercise. The results of these studies show comparable beta-endorphin levels with high-intensity exercise without BFR and low-intensity exercise with BFR. Low-intensity training with BFR had greater local pain relief, perhaps indicating the promising effects of BFR in enhancing EIH. By reviewing the current literature on this topic, we hope that further progress can be made to better understand the mechanism behind BFR and its ability to enhance EIH. Currently, local metabolites are a major focus for the potential mechanism behind these effects. Mas-related G-protein-coupled receptors (Mrgprs) contribute to local pain pathways via mast cell degranulation. Similarly, chemokine receptor 2/chemokine ligand 2 (CCR2/CCL2) triggers mast cell degranulation and inflammation-induced pain. Finally, pain-reducing effects have been linked to anti-inflammatory IL-10 signaling and anaerobic metabolites via transient receptor potential vanilloid 1 (TRPV1). Through a better understanding of these metabolites and their mechanisms, it is possible to further exploit the use of BFR to not only serve athletes recovering from injury but also apply this information to better serve all patients.

Modulation of pain perceptions following treadmill running with different intensities in females.

We aimed to compare the effects of three intensities of treadmill running on exercise-induced hypoalgesia (EIH) in healthy individuals. We anticipated that the primary and secondary changes in pain perception and modulation may differ between running intensities. Sixty-six women were randomly assigned to one of three treadmill running intensities for 35 min: 40% reserved heart rate (HRR), 55% HRR, or 70% HRR. The effects of EIH were assessed using pressure pain thresholds (PPT) and tolerance thresholds (PPTol). We measured conditional pain modulation (CPM). Compared with baseline, PPT and PPTol significantly increased in all groups during running and at the 5-10-min follow-up. The PPT and PPTol changes in the moderate- and low-intensity groups were significantly higher than those in the high-intensity group during running and 24 h after running, while the CPM responses of the high-intensity group were significantly reduced at the 24-h follow-up. Moderate- and low-intensity running may elicit significant primary and secondary (persisting over 24 h) EIH effects and increase CPM responses in females. However, high-intensity running induced only limited analgesic effects and reduced CPM responses, which may be attributed to the activation of endogenous pain modulation.

Unravelling Impaired Hypoalgesia at Rest and in Response to Exercise in Patients with Chronic Whiplash-Associated Disorders: Effects of a Single Administration of Selective Serotonin Reuptake Inhibitor versus Selective Norepinephrine Reuptake Inhibitor.

(1) Background: Noradrenaline and serotonin have modulatory roles in pain signaling and in exercise-induced hypoalgesia. Patients with chronic whiplash-associated disorders often show impaired exercise-induced hypoalgesia. Therefore, this study aimed to examine the isolated effect of activating serotonergic or noradrenergic descending pathways on hypoalgesia at rest and in response to exercise in patients with chronic WAD by using respectively a single dose of a selective serotonin reuptake inhibitor (SSRI) and a selective norepinephrine reuptake inhibitor (NRI). (2) Methods: Twenty-five people with chronic WAD participated in this double-blind randomized controlled crossover experiment. Serotonin and noradrenaline concentrations were modulated by the oral ingestion of a single dose of citalopram (i.e., SSRI) or atomoxetine (i.e., SNRI). Quantitative sensory testing (including pressure pain thresholds and conditioned pain modulation) was measured before and after exercise in combination with no medication (1), atomoxetine (2), or citalopram (3) at three different test days. (3) Results: Random-intercept linear mixed models analysis was used to analyze pain outcomes (i.e., pain at rest and exercise-induced hypoalgesia) before and after exercise over the three conditions in patients with chronic WAD. No differences in pain at rest were found between the three conditions before exercise. The effect of exercise on pain outcome measures was not influenced by medication intake. The occupational status of the participants had a significant influence on the effect of exercise and medication on pain outcomes (p < 0.05). Patients working full-time had some positive effect of atomoxetine on pain facilitation (p < 0.05). Unemployed patients had some negative effect of citalopram on pain tolerance and experienced exercise-induced hypoalgesia (p < 0.05). (4) Conclusions: A single dose of citalopram or atomoxetine did not result in changes in hypoalgesia at rest and in response to exercise. These results do not support the use of SSRI or selective NRI to overcome impaired hypoalgesia at rest or in response to exercise in people with chronic WAD. Effect of exercise and medication on pain in patients with chronic WAD is influenced by the occupational status.

Can we improve exercise-induced hypoalgesia with exercise training? An overview and suggestions for future studies.

Exercise-induced hypoalgesia refers to a reduction in pain sensitivity following a single bout of exercise, which has been shown to be diminished or impaired with aging and chronic pain. Exercise training (repeated bouts of exercise over time) is often recommended as a non-pharmacological treatment for chronic pain and age-related functional declines. However, whether exercise training can augment the exercise-induced hypoalgesia has not been well studied. The purpose of this paper is to 1) provide an overview of the existing literature investigating the effect of exercise training on the magnitude of exercise-induced hypoalgesia, and 2) discuss potential underlying mechanisms as well as considerations for future research. Given the paucity of randomized controlled trials in this area, the effects of exercise training on exercise-induced hypoalgesia are still unclear. Several potential mechanisms have been proposed to explain the impaired exercise-induced hypoalgesia in chronic pain and older individuals (e.g., endogenous opioid, cardiovascular, and immune system). Exercise training appears to induce physiological changes in those systems, however, further investigations are necessary to test whether this will lead to improved exercise-induced hypoalgesia. Future research should consider including a time- and age-matched non-training group and utilizing the same exercise protocol for testing exercise-induced hypoalgesia across intervention groups.

Pain intensity and pain sensitivity are not increased by a single session of high-intensity interval aerobic exercise in individuals with chronic low back pain: A randomized and controlled trial.

BACKGROUND: Evidence on the acute impact of high-intensity interval aerobic exercise on pain is scarce. This type of exercise might be perceived as increasing pain intensity and pain sensitivity negatively impacting adherence. More evidence on the acute effects of high-intensity interval aerobic exercise in individuals with low back pain (LBP) is needed. OBJECTIVES: To compare the acute effects of a single session of high-intensity interval aerobic exercise, continuous moderate-intensity aerobic exercise, and no exercise on pain intensity and pain sensitivity in patients with chronic non-specific LBP. DESIGN: Randomized controlled trial with three arms. METHOD: Participants were randomly assigned to one of three groups (i) continuous moderate-intensity aerobic exercise, ii) high-intensity interval aerobic exercise, and iii) no intervention. Measures of pain intensity and pressure pain threshold (PPT) at the lower back and at a distant body site (upper limb) were taken before and after 15 min of exercise. RESULTS: Sixty-nine participants were randomized. A significant main effect of time was found for pain intensity (p = 0.011; η2p = 0.095) and for PPT at the lower back (p < 0.001; η2p = 0.280), but not a time versus group interaction (p > 0.05). For PPT at the upper limb, no main effect of time or interaction was found (p > 0.5). CONCLUSIONS: Fifteen minutes of high-intensity interval aerobic exercise does not increase pain intensity or pain sensitivity compared to both moderate-intensity continuous aerobic exercise and no exercise, suggesting that high-intensity interval aerobic exercise can be used in clinical practice and patients reassured that it is unlikely to increase pain.

Elucidation of the mechanisms of exercise-induced hypoalgesia and pain prolongation due to physical stress and the restriction of movement.

Persistent pain signals cause brain dysfunction and can further prolong pain. In addition, the physical restriction of movement (e.g., by a cast) can cause stress and prolong pain. Recently, it has been recognized that exercise therapy including rehabilitation is effective for alleviating chronic pain. On the other hand, physical stress and the restriction of movement can prolong pain. In this review, we discuss the neural circuits involved in the control of pain prolongation and the mechanisms of exercise-induced hypoalgesia (EIH). We also discuss the importance of the mesolimbic dopaminergic network in these phenomena.

The role of spontaneous vs. experimentally induced attentional strategies for the pain response to a single bout of exercise in healthy individuals.

OBJECTIVES: Exercise-induced pain and exercise-induced hypoalgesia (EIH) are well described phenomena involving physiological and cognitive mechanisms. Two experiments explored whether spontaneous and instructed mindful monitoring (MM) were associated with reduced exercise-induced pain and unpleasantness, and increased EIH compared with spontaneous and instructed thought suppression (TS) in pain-free individuals. METHODS: Eighty pain-free individuals participated in one of two randomized crossover experiments. Pressure pain thresholds (PPTs) were assessed at the leg, back and hand before and after 15 min of moderate-to-high intensity bicycling and a non-exercise control condition. Exercise-induced pain and unpleasantness were rated after bicycling. In experiment 1 (n=40), spontaneous attentional strategies were assessed with questionnaires. In experiment 2, participants (n=40) were randomly allocated to use either a TS or MM strategy during bicycling. RESULTS: In experiment 1, the change in PPTs was significantly larger after exercise compared with quiet rest (p<0.05). Higher spontaneous MM was associated with less exercise-induced unpleasantness (r=-0.41, p<0.001), whereas higher spontaneous TS was associated with higher ratings of exercise-induced unpleasantness (r=0.35, p<0.05), but not with pain intensity or EIH. In experiment 2, EIH at the back was increased in participants using instructed TS compared with participants using instructed MM (p<0.05). CONCLUSIONS: These findings suggest that spontaneous and presumably habitual (or dispositional) attentional strategies may primarily affect cognitive-evaluative aspects of exercise, such as feelings of exercise-induced unpleasantness. MM was related to less unpleasantness, whereas TS was related to higher unpleasantness. In terms of brief experimentally-induced instructions, TS seems to have an impact on physiological aspects of EIH; however, these preliminary findings need further research.

The effects of a 15-week physical exercise intervention on pain modulation in fibromyalgia: Increased pain-related processing within the cortico-striatal- occipital networks, but no improvement of exercise-induced hypoalgesia.

Dysfunctional top-down pain modulation is a hallmark of fibromyalgia (FM) and physical exercise is a cornerstone in FM treatment. The aim of this study was to explore the effects of a 15-week intervention of strengthening exercises, twice per week, supervised by a physiotherapist, on exercise-induced hypoalgesia (EIH) and cerebral pain processing in FM patients and healthy controls (HC). FM patients (n = 59) and HC (n = 39) who completed the exercise intervention as part of a multicenter study were examined at baseline and following the intervention. Following the exercise intervention, FM patients reported a reduction of pain intensity, fibromyalgia severity and depression. Reduced EIH was seen in FM patients compared to HC at baseline and no improvement of EIH was seen following the 15-week resistance exercise intervention in either group. Furthermore, a subsample (Stockholm site: FM n = 18; HC n = 19) was also examined with functional magnetic resonance imaging (fMRI) during subjectively calibrated thumbnail pressure pain stimulations at baseline and following intervention. A significant main effect of exercise (post > pre) was observed both in FM patients and HC, in pain-related brain activation within left dorsolateral prefrontal cortex and caudate, as well as increased functional connectivity between caudate and occipital lobe bordering cerebellum (driven by the FM patients). In conclusion, the results indicate that 15-week resistance exercise affect pain-related processing within the cortico-striatal-occipital networks (involved in motor control and cognition), rather than directly influencing top-down descending pain inhibition. In alignment with this, exercise-induced hypoalgesia remained unaltered.

The autonomic and nociceptive response to acute exercise is impaired in people with knee osteoarthritis.

Objectives: An acute bout of exercise typically leads to short term exercise induced hypoalgesia (EIH), but this response is more variable in many chronic pain populations, including knee osteoarthritis (OA) and fibromyalgia (FM). There is evidence of autonomic nervous system (ANS) dysfunction in some chronic pain populations that may contribute to impaired EIH, but this has not been investigated in people with knee OA. The aim of this study was to assess the acute effects of isometric exercise on the nociceptive and autonomic nervous systems in people with knee OA and FM, compared to pain-free controls. Methods: A cross-sectional study was undertaken with 14 people with knee OA, 13 people with FM, and 15 pain free controls. Across two experimental sessions, baseline recordings and the response of the nociceptive and autonomic nervous systems to a 5-min submaximal isometric contraction of the quadriceps muscle was assessed. The nociceptive system was assessed using pressure pain thresholds at the knee and forearm. The ANS was assessed using high frequency heart rate variability, cardiac pre-ejection period, and electrodermal activity. Outcome measures were obtained before and during (ANS) or immediately after (nociceptive) the acute bout of exercise. Results: Submaximal isometric exercise led to EIH in the control group. EIH was absent in both chronic pain groups. Both chronic pain groups showed lower vagal activity at rest. Furthermore, people with knee OA demonstrated reduced vagal withdrawal in response to acute isometric exercise compared to controls. Sympathetic reactivity was similar across groups. Discussion: The findings of reduced tonic vagal activity and reduced autonomic modulation in response to isometric exercise raise the potential of a blunted ability to adapt to acute exercise stress and modulate nociception in people with knee OA. The impairment of EIH in knee OA may, in part, be due to ANS dysfunction.

Assessment of exercise-induced hypoalgesia in chronic low back pain and potential associations with psychological factors and central sensitization symptoms: A case-control study.

INTRODUCTION: Exercise is the most recommended treatment for chronic low back pain (CLBP) and is effective in reducing pain, but the mechanisms underlying its effects remain poorly understood. Exercise-induced hypoalgesia (EIH) may play a role and is thought to be driven by central pain modulation mechanisms. However, EIH appears to be disrupted in many chronic pain conditions and its presence in people with CLBP remains unclear. As people suffering from chronic pain often exhibit psychological factors and central sensitization symptoms influencing pain perception, EIH might be associated with these factors. OBJECTIVE: The aim of this study is to compare the level of EIH between participants with and without CLBP following back and wrist exercises and to assess the associations between EIH, psychological factors, and symptoms of central sensitization (using the central sensitization inventory - CSI) in CLBP. METHOD: Twenty-eight participants with CLBP and 23 without pain were recruited. Pressure pain thresholds (PPT) were measured at 4 sites (2 bony sites = capitate, S1|2 muscle sites = wrist flexors, lumbar erector spinae) before and after each of two exercises (wrist flexion and lumbar extension). Exercise-induced hypoalgesia was defined as percent change in PPT from pre- to post-exercise. Participants with CLBP also completed questionnaires to measure psychological factors (e.g., kinesiophobia, catastrophizing, anxiety, and self-efficacy) and symptoms of central sensitization (CSI), and correlations with EIH were calculated. RESULTS: After wrist exercise, EIH measured at the muscle sites was lower in the CLBP group compared with the pain-free group (p = 0.047) but no differences were found at bony sites (p = 0.49). No significant differences for EIH were observed following back exercise at muscle sites (p = 0.14) or at bony sites (p = 0.65). Exercise-induced hypoalgesia was not correlated with any psychological factors or with the CSI score. CONCLUSION: The lower EIH following wrist exercises may represent an alteration in pain modulation control in CLBP. However, psychological factors and central sensitization symptoms may not explain the differences observed.

Response to experimental cold-induced pain discloses a resistant category among endurance athletes, with a distinct profile of pain-related behavior and GABAergic EEG markers: a case-control preliminary study.

Pain is a major public health problem worldwide, with a high rate of treatment failure. Among promising non-pharmacological therapies, physical exercise is an attractive, cheap, accessible and innocuous method; beyond other health benefits. However, its highly variable therapeutic effect and incompletely understood underlying mechanisms (plausibly involving the GABAergic neurotransmission) require further research. This case-control study aimed to investigate the impact of long-lasting intensive endurance sport practice (≥7 h/week for the last 6 months at the time of the experiment) on the response to experimental cold-induced pain (as a suitable chronic pain model), assuming that highly trained individual would better resist to pain, develop advantageous pain-copying strategies and enhance their GABAergic signaling. For this purpose, clinical pain-related data, response to a cold-pressor test and high-density EEG high (Hß) and low beta (Lß) oscillations were documented. Among 27 athletes and 27 age-adjusted non-trained controls (right-handed males), a category of highly pain-resistant participants (mostly athletes, 48.1%) was identified, displaying lower fear of pain, compared to non-resistant non-athletes. Furthermore, they tolerated longer cold-water immersion and perceived lower maximal sensory pain. However, while having similar Hß and Lß powers at baseline, they exhibited a reduction between cold and pain perceptions and between pain threshold and tolerance (respectively -60% and - 6.6%; -179.5% and - 5.9%; normalized differences), in contrast to the increase noticed in non-resistant non-athletes (+21% and + 14%; +23.3% and + 13.6% respectively). Our results suggest a beneficial effect of long-lasting physical exercise on resistance to pain and pain-related behaviors, and a modification in brain GABAergic signaling. In light of the current knowledge, we propose that the GABAergic neurotransmission could display multifaceted changes to be differently interpreted, depending on the training profile and on the homeostatic setting (e.g., in pain-free versus chronic pain conditions). Despite limitations related to the sample size and to absence of direct observations under acute physical exercise, this precursory study brings into light the unique profile of resistant individuals (probably favored by training) allowing highly informative observation on physical exercise-induced analgesia and paving the way for future clinical translation. Further characterizing pain-resistant individuals would open avenues for a targeted and physiologically informed pain management.

Effects of Exercise-Induced Hypoalgesia at Different Aerobic Exercise Intensities in Healthy Young Adults.

Purpose: Exercise-induced hypoalgesia (EIH) is a reduction in pain sensitivity that occurs following a single bout of exercise. However, little research has compared the EIH effects of exercise at different intensities, including low intensity, in the same participant. It is unclear as to which exercise intensities demonstrate EIH more effectively. The aim of this study was to examine and compare the effect of different intensities of exercise on pain sensitivity in the same participant. Methods: We included 73 healthy young adult volunteers (35 female and 38 male) in this experimental cross-over study. Each participant completed four experimental sessions of 30 min, consisting of aerobic exercise at 30% heart rate reserve (HRR), aerobic exercise at 50% HRR, aerobic exercise at 70% HRR, and quiet rest. EIH was assessed using the pressure pain threshold (PPT) and temporal summation of pain (TSP) in the quadriceps, biceps, and trapezius. Results: Low- and moderate-intensity exercise increased the multisegmental PPT and reduced TSP (all P < 0.05). High-intensity exercise increased the multisegmental PPT (all P < 0.05), but decreased TSP in only the quadriceps and biceps (P < 0.05), not the trapezius (P = 0.13). We found no difference in relative PPT and TSP changes between exercise intensities (P > 0.05) except for relative PPT change at the quadriceps (P < 0.05). Conclusion: Our results show that not only moderate- and high-intensity exercise, but also low-intensity exercise can produce a hypoalgesic response.