Exercise-induced hypoalgesia in temporomandibular disorders—a narrative review of literature

Introduction

Temporomandibular joint disorder (TMD) is an umbrella term for musculoskeletal conditions associated with pain and/or functional dysfunction involving the temporomandibular joint (TMJ), masticatory muscles, and related anatomical structures (1,2). Temporomandibular disorders (TMDs) are a significant public health problem, with prevalence estimates ranging from 7% to 30% in adolescents and approximately 5–12% in the general population, making them the most common cause of chronic nondental orofacial pain (3,4). Although the term “temporomandibular disorders” encompasses both joint-related (arthrogenous) and muscle-related (myogenous) conditions, the current review includes evidence across these subtypes, reflecting their overlapping mechanisms and shared clinical relevance. A patient with TMD presents with a multitude of symptoms, including facial pain, TMJ pain, neck pain, jaw popping or clicking, limited mandibular range of motion, headache, and tinnitus, thereby compromising an individual’s daily functional activities (2,5). The possible causes for TMDs are micro- and macro-trauma, occlusal overloading, increased joint friction, dental malocclusion, functional shift, stress, anxiety, and depression (6,7). In addition, recent findings confirm that the lateral pterygoid muscle exhibits variable attachment patterns to the disc and dorsal capsular complex, which may contribute to internal derangement of the TMJ (8). However, current evidence supports that TMD etiology is multifactorial and best explained through a biopsychosocial model, involving the interaction between biological, psychological, and social factors. Large-scale prospective studies such as the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project have identified somatic symptom burden, poor sleep quality, genetic vulnerability, and stress-related mechanisms as significant predictors of TMD development (9). Moreover, bruxism is no longer regarded as a parafunctional habit but rather as a sleep or awake motor behavior that may act as a risk, protective, or neutral factor for orofacial pain (10). Recent studies emphasize the role of central sensitization (CS) in chronic TMDs, characterized by amplified central pain processing and reduced inhibitory control. Evidence shows that patients with TMD exhibit lower pressure pain thresholds (PPTs) and greater somatization associated with enhanced CS and masticatory muscle pain, reflecting disturbed descending modulation and neuroplastic changes. These findings support a biopsychosocial neurophysiological framework for understanding persistent TMD pain (11,12).

Exercise therapy has been widely studied in chronic musculoskeletal pain conditions such as fibromyalgia, low-back pain, and myofascial pain (13-16). This transient reduction in pain sensitivity after physical activity, known as exercise-induced hypoalgesia (EIH), may, however, vary across individuals, and in some chronic pain populations, pain sensitivity can remain unchanged or even increase (14,17). EIH is thought to involve complex interactions among the opioid, endocannabinoid, serotonergic, and hypothalamic-pituitary-adrenal systems (18-20), and is further influenced by sex-related and psychosocial factors (18,21-24). Although these mechanisms have been described in generalized chronic pain disorders, their specific relevance to temporomandibular disorders remains insufficiently understood (19).

Myalgia has been reported as the most frequent chronic pain condition in TMDs, resulting in peripheral sensitization (25,26). Current reports suggest that both pain amplification, which may occur due to peripheral and CS mechanisms, and dysfunctional pain inhibition can contribute to chronic TMJ pain (27). van Grootel et al. elucidated the role of myogenous (external trauma or injury that may initiate peripheral sensitization of nociceptors in masticatory muscles), psychobiological (CS induced by dysfunctional descending pain facilitation and inhibition systems), and psychosocial factors (stress, emotion, and somatic awareness) in the aetiology of TMDs (28). Multimodal management strategies such as non-surgical conservative treatment (patient education, self-care techniques, jaw and neck exercises, intraoral appliances, pharmacological and physical therapies, psychological interventions) and invasive surgical treatment are available to treat TMD patients with variable success rates; however, primarily conservative multidisciplinary treatment is recommended due to the complexity of TMDs (29,30). In addition, new treatment strategies that include photo biomodulation, acupuncture, and combination strategies (photo biomodulation-acupuncture) have shown promising therapeutic outcomes, including decreased pain intensity, improved function, and improved quality of life in TMD patients. However, limitations remain, as evidence has not been consistently pooled, certainty is low, and heterogeneity in PBMT protocols makes it challenging to establish a standard treatment approach (31-37). Different exercises, such as aerobic, isometric resistance, and exercises to improve muscle strength and flexibility, can reduce widespread peripheral sensitization (38). Aerobic exercise (AE) and static muscle contraction have hypoalgesic effects, elevate pressure-pain thresholds, and reduce pain perception in patients with myofascial pain and chronic musculoskeletal pain (27).

Rationale and knowledge gap

TMDs are common non-odontogenic orofacial pain conditions, affecting the masticatory muscles (myogenous TMDs) and the TMJ (arthrogenous TMDs) (39). Pain aggravated by manipulation or jaw function, and mandibular dysfunction involving limitations in mouth opening, impacts patients’ quality of life (1). As TMD is a psycho-physiological disorder with complex and multifactorial aetiology, the treatment of TMDs requires a multidisciplinary approach to manage chronic pain (40). Conservative, reversible treatment is preferred for the initial management of TMDs; therefore, home care and exercise therapies are considered safe and effective treatment options for improving an individual’s painful symptoms and motor function (41). Exercise interventions, such as high-intensity AE, have pain-relieving effects in pain-free subjects, a phenomenon referred to as EIH (14). Clinical reductions in pain are usually observed after 8 to 12 weeks of exercise, and a single exercise session can also produce EIH (19). A single bout of aerobic or resistance exercise increases pain threshold and tolerance in pain-free individuals, with effects lasting up to 30 minutes post-exercise. Still, results are variable in chronic pain populations, with pain sensitivity decreasing, remaining unchanged, or, in some cases, increasing in response to an acute bout of physical activity or exercise (14,19). The aggravation of painful symptoms reduces patients’ adherence to exercise training programs, eventually worsening their pain and associated disability (42). Current evidence for exercise therapy in chronic TMD pain remains weak and inconsistent (27,38,42). While some studies report benefits, others show impaired or variable EIH responses (14,19). Further clinical research is needed to identify the most effective exercise modalities, including optimal dose, intensity, and duration (27,38), and to develop clear guidelines for non-pharmacological management of TMDs (42). Developing recommended guidelines for non-pharmacological approaches to managing TMD patients is essential to improve patient adherence to the specific exercise program.

Objective

This review aims to explore the effects of physical activity and exercise on reducing pain intensity in patients with chronic TMD pain. It also summarizes the literature on possible biological mechanisms of EIH, provides an overview of gender differences in EIH, and examines the influence of the immune system and psychosocial factors on EIH in healthy, pain-free individuals and in subjects with musculoskeletal pain, including TMD. We present this article in accordance with the Narrative Review reporting checklist (available at https://joma.amegroups.com/article/view/10.21037/joma-25-14/rc).

Methods

Search strategy and data extraction

Two authors (R.N. and J.K.) independently searched for relevant literature up to March 2025 by using PubMed, Scopus, Web of Science, Cochrane Library, and Embase electronic databases and a combination of keywords based on Medical Subject Headings (MeSH), such as “temporomandibular joint”, “TMJ”, “temporomandibular disorders”, “temporomandibular joint disorders”, “pain”, “exercise”, and “hypoalgesia”. Screening of titles and selection of relevant literature for inclusion in this review were carried out by two authors (J.K. and R.N.) and cross-checked by other authors (A.K., M.E., S.S.K., and G.S.S.). Any disagreement was resolved by mutual discussion between the authors until a consensus was reached (Tables 1,2, and Figure 1).

Figure 1 Flow chart of included studies. EIH, exercise-induced hypoalgesia; TMD, temporomandibular disorders.

Eligibility criteria

Inclusion criteria included case reports, case series, original research, short communications, and reviews on EIH after exercise in TMDs and chronic pain musculoskeletal conditions published in English to avoid bias. Original research articles detailing the results of clinical studies, descriptive surveys, cross-sectional studies, randomized controlled trials, retrospective or prospective cohort studies, case-control studies, in vitro studies, and animal studies were considered. In contrast, letters to the editor and commentaries were excluded (Table 2 and Figure 1). Inclusion of lower-level evidence (e.g., case reports, case series) may increase bias, and restriction to English-language studies may introduce language bias. A total of 8,092 records were identified across the databases. After duplicate removal and screening, 8 studies met the inclusion criteria and were included in this narrative review. All tables and figures included in this manuscript are original and created by the authors.

Methodological quality appraisal

The methodological quality of this narrative review was guided by the Joanna Briggs Institute (JBI) checklist for narrative reviews (43). The review question, inclusion criteria, and search strategy were clearly defined. Two reviewers independently screened and appraised the studies; sources were considered appropriate, and methods were transparently reported. Although quantitative pooling was not attempted, the likelihood of publication bias was considered low given the comprehensive search strategy.

Discussion

Biological mechanisms for EIH in chronic pain conditions

Investigators have reported elevated pain thresholds and reduced pain during and after single episodes of exercise in healthy young adults. Additionally, exercise could also promote analgesia in chronic pain conditions such as low back pain, fibromyalgia, osteoarthritis, myofascial pain, and chronic fatigue syndrome (44). Previous literature has described the therapeutic effects of various modes of exercise, including AE (running, cycling), resistance exercise (weight lifting), and isometric exercise (static muscle contractions), in reducing pain perception and improving an individual’s psychological health (44). Moleirinho-Alves et al., in a prospective clinical study, observed an increase in PPT and a decrease in Numeric Rating Scale (NRS) score in muscular TMD patients 30 minutes after therapeutic exercises (45). De la Corte-Rodriguez et al. stated that when a healthy, pain-free subject performs an acute bout of exercise, a period of hypoalgesia ensues, with a decrease in sensitivity to painful stimuli of variable duration, and, in athletes, a reduction in pain sensitivity is observed after 120 minutes of AE (46). Sluka et al., in a review, referred to physical inactivity as the “diseasome of physical inactivity” and considered it a potential risk factor for pain, whereas physical activity reduces the risk (18).

For chronic pain, exercise and physical therapy have been recognized as an effective and safe therapeutic approach with fewer adverse effects than pharmacological or invasive surgical treatment modalities in reducing pain intensity, associated disability, and health care costs (18,44). Contrary to this, exercise has been observed to increase or exacerbate pain in experimental and clinical settings, mainly when a musculoskeletal pain is already established. Dailey et al. (47) reported that people with fibromyalgia had increases in pain and fatigue after completion of a cognitive and physical fatigue task or a dual fatigue task (P<0.001) compared to healthy controls. Vaegter et al. reported an association between pain flares and impaired EIH in chronic pain conditions. Almost 30% of participants with lower back pain showed increased clinical pain and pain sensitivity, and reduced EIH during walking (48). Pain flares during physical activity in patients with low back pain may result from facilitation of pronociceptive mechanisms and impaired conditioned pain modulation (CPM), suggesting that when CPM is impaired, exercise or physical activity results in milder hypoalgesic effects (48). Therefore, participation in rehabilitation can be challenging for the chronic pain patient due to an increase in pain following exercise (18). The exact underlying mechanisms responsible for EIH are still not precise, and evidence from animal studies has revealed multiple biological mechanisms, including opioid and non-opioid systems, leading to variations in pain response (exacerbation or increase) to exercise.

Endogenous opioid system

The endogenous opioid system is one of the most investigated mechanisms underlying EIH. Exercise stimulates the release of β-endorphins and enkephalins, which act on opioid receptors at peripheral, spinal, and supraspinal sites to reduce pain perception (49-51). Human and animal studies support this pathway; for example, β-endorphin release has been demonstrated in response to moderate-intensity exercise and has been linked to mesolimbic dopaminergic activation (51). However, the role of opioids is not exclusive. Studies administering the opioid antagonist naltrexone before exercise found persistent hypoalgesic effects in some participants, indicating that opioid-insensitive mechanisms also contribute to EIH (50,52). These findings emphasize that while endogenous opioids contribute significantly to analgesic responses, they cannot fully explain the variability observed across individuals and chronic pain populations. Variability in opioid responsiveness suggests that some patients with TMD or other chronic pain conditions may require tailored exercise prescriptions, as opioid-mediated pathways alone may not determine treatment benefit.

Endocannabinoid system

The endocannabinoid system has also been recognized as a non-opioid pathway contributing to EIH. Exercise elevates circulating concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), which bind to cannabinoid cannabinoid receptor type 1 (CB1) receptors in pain-processing regions of the brain and spinal cord, producing analgesic effects (50,52-54). Increases in related lipids such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) have also been reported following isometric exercise (50). Experimental trials indicate partial overlap with opioid mechanisms: Crombie et al. found that naltrexone pretreatment blocked increases in AEA and OEA, but not in 2-AG and 2-oxoglutarate (2-OG), suggesting a complex interaction between systems (52). Importantly, reduced CB1 activation and impaired endocannabinoid signaling have been observed in chronic pain states (14), which may explain the inconsistent EIH response in clinical populations. Activation of the endocannabinoid system by moderate-intensity exercise may account for beneficial effects even when opioid-mediated pathways are insufficient, highlighting the importance of dose selection in exercise programs for TMD patients.

CPM and temporal summation

CPM reflects the efficiency of descending inhibitory systems, often described as the “pain inhibits pain” phenomenon. CPM is typically reduced in patients with chronic pain conditions such as fibromyalgia, low back pain, and TMD (55-57). Evidence shows that individuals with stronger CPM responses are more likely to experience robust EIH. In contrast, those with impaired CPM may experience reduced or even paradoxical increases in pain during exercise (55,58).

Temporal summation of pain (TSP), in contrast, reflects central pronociceptive processes; repetitive noxious stimulation can amplify second-order neuronal activity in the dorsal horn (“wind-up”), leading to hyperalgesia (59-61). Exaggerated TSP has been linked to poor analgesic response and may coexist with reduced CPM in chronic pain cohorts (62). Together, CPM and TSP can serve as potential biomarkers to predict who may benefit most from exercise interventions. Vaegter et al. reported that nearly 30% of patients with low back pain experienced pain flares and reduced EIH during walking, linking impaired CPM with activity-related exacerbations (48). Petersen et al. demonstrated variability in modulation profiles, with fibromyalgia and osteoarthritis patients more often presenting with high TSP and low CPM, indicating central pain dysregulation (63). In TMJ pain, Zhang et al. showed that repeated jaw movements amplified pain scores over time compared to controls, consistent with facilitated temporal summation in craniofacial muscles (64).

Ye et al. showed that EIH and CPM involve partly overlapping but distinct inhibitory pathways: isometric wall-squat exercise and cold-water immersion each produced hypoalgesia. At the same time, their combination yielded the most potent pain inhibition, suggesting additive descending control (65). Subsequent studies confirmed CPM as a reliable psychophysical biomarker reflecting the net efficiency of descending pain modulation and as a predictor of treatment response in chronic pain patients (66,67). TSP represents the opposite—facilitatory—aspect of central processing; repetitive noxious stimulation above 0.3 Hz can amplify dorsal horn neuronal activity (“wind-up”), leading to hyperalgesia (67). Increased TSP and reduced CPM often coexist in chronic pain syndromes and have been associated with a greater risk of postoperative pain, poor analgesic response, and suboptimal outcomes from exercise-based therapies (63). In orofacial pain, TSP appears particularly relevant: females with TMD show up-regulated temporal summation, and Zhang et al. (64) reported progressive pain amplification during repeated jaw-movement tasks compared with controls, indicating heightened central excitability. These findings highlight that evaluating both CPM and TSP may help clinicians individualize exercise intensity and anticipate which TMD patients are prone to pain flares or limited hypoalgesic benefit.

Autonomic nervous system in EIH

The autonomic nervous system (ANS) plays a key role in modulating pain. It is frequently altered in conditions such as fibromyalgia, rheumatoid arthritis, irritable bowel syndrome, and complex regional pain syndrome (68). In healthy individuals, acute pain activates sympathetic outflow as an adaptive response that suppresses nociceptive transmission via descending inhibition (59). In contrast, chronic pain is characterized by reduced vagal tone and persistent sympathetic overactivity, resulting in impaired autonomic adaptability to stress and noxious stimuli (10,14,68,69). This dysregulation contributes to higher pain sensitivity and reduced thresholds to sympathetic stimulation (70).

Rice et al. reported that lower parasympathetic activity, rather than excessive sympathetic drive, correlates with higher pain intensity in widespread chronic pain. In healthy subjects, elevated blood pressure induces hypoalgesia, whereas in chronic pain, the same hemodynamic change enhances pain perception, likely reflecting altered baroreceptor reflexes (14). Animal studies further support this mechanism: hypertension-induced hypoalgesia has been described in rats, and regular exercise—such as wheel running or treadmill training—restores baroreceptor sensitivity, reduces heart rate, and prevents autonomic dysfunction (60,61).

Heart-rate variability (HRV) is the leading indicator of ANS balance; higher HRV reflects greater parasympathetic modulation, while low HRV denotes sympathetic predominance (71). Evidence suggests that moderate AE improves HRV and post-exercise hypotension, enhancing parasympathetic tone (61). Although data remain limited, studies indicate that impaired autonomic regulation may underlie the variability in EIH, as reduced cardiovascular adaptability correlates with blunted hypoalgesic responses (14). Gradual, sustained AE appears beneficial for restoring autonomic balance and may enhance endogenous pain-inhibitory capacity in patients with TMD and other chronic musculoskeletal disorders.

Psychological factors in EIH

Psychological factors may modulate the EIH response in pain-free and chronic pain populations. Depression, anxiety, catastrophizing, and kinesiophobia have been associated with greater pain sensitivity and smaller EIH responses, although findings are inconsistent across conditions (66,72,73). Experimental work also implicates stress-related neuroendocrine pathways: EIH has been linked to growth hormone release during exercise, yet Kemppainen et al. reported dental pain-threshold elevation not explained by GH; moreover, dexamethasone blunted exercise-induced ACTH release and attenuated analgesia (48,74,75). In chronic pain cohorts, several studies found no clear association between psychological variables and changes in PPT after exercise, and self-paced exercise may function as a physiological/psychological stressor that can exacerbate symptoms in some patients (14). Overall, psychological influences on EIH remain uncertain and likely vary by population, outcome, and exercise paradigm (14,66,72-75).

Immune system in EIH

Exercise can trigger immune responses, with inflammation recognized as a feature of chronic musculoskeletal pain (14,76). Pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) may sensitize nociceptors, and a single bout of exercise can elicit variable inflammatory cascades depending on the type and intensity of the exercise (77,78). While excessive intensity may provoke immune activation, moderate exercise has been described as a potential long-term anti-inflammatory strategy (77). Overall, evidence linking immune alterations with post-exercise pain or impaired EIH remains inconclusive, and further clinical studies are needed (14,77,78).

Sex differences in EIH

Sex differences in pain are well documented, with women generally reporting greater sensitivity and higher prevalence of chronic pain conditions (14,78). Biological and psychosocial factors, including sex hormones, coping, and mood disturbances, are thought to contribute (26,79,80). Estrogen may promote inflammation in TMJ structures, whereas testosterone in men may have anti-nociceptive effects (26,79). Findings on sex differences in EIH, however, are inconsistent: some studies report impaired responses in women, while others show comparable or even greater hypoalgesia compared with men (14,78). Overall, the role of sex in EIH remains unclear and requires further targeted research.

Chronic pain in TMDs

Persistent pain in TMD is common and can lead to an increase in emotional distress, maladaptive thoughts and behaviour, functional disability, pain-related disability, and interfere with daily activities (81,82). Chronic TMDs often co-exist with chronic overlapping pain conditions (COPC), such as fibromyalgia, chronic migraine, tension-type headache, chronic lower back pain, and irritable bowel syndrome (83). Herrero Babiloni et al. reported that painful TMD patients could also present with pain fluctuations over time, and changes in pain intensity of at least 20 in a 0–100 pain scale have been identified in TMD patients in both short- and long-term periods (84). Several factors, including stress, menstrual cycle, weather, and treatment strategy, could contribute to pain fluctuations. Still, the literature on pain fluctuations and their determinants in painful TMDs is limited (84). The Graded Chronic Pain Scale (GCPS) is widely used to assess pain-related disability, measure chronic pain intensity, and differentiate between low and high impact pain (84,85). Individuals with high-impact TMD pain can have higher levels of physical and psychological symptoms. In contrast, individuals with low-impact TMD pain have lower psychological distress, better ability to cope with pain, and have favourable treatment outcomes (84). High-impact TMD patients had 5 times the odds of experiencing short-term jaw pain fluctuations than low-impact TMD patients (P=0.03), and these fluctuations were not correlated with PPT fluctuations, indicating complex, diverse mechanisms responsible for short-term pain fluctuations (84). Miller et al. reported that the characteristics that differ between high and low impact TMD pain patients include clinical pain features and the ability to cope with pain. One-third of chronic TMD patients were found to experience high-impact pain associated with jaw limitation, catastrophizing, and painful body sites (86). To address the clinical differences in chronic pain, a simplified GCPS Revised (GCPS-R) was developed, which grades chronic pain severity as mild, bothersome, and high-impact chronic pain (87). CS has been implicated in the pathophysiology of chronic TMD pain, leading to increased pain responses to noxious stimuli (hyperalgesia) and to non-noxious stimuli (allodynia) (88).

Upregulation of the autonomic nervous system, characterized by high sympathetic tone even at rest, could contribute to the chronicity of TMD pain (83). As a result, TMD patients have decreased response to physical and psychological stressors and have low cardiac parasympathetic tone at all times compared to healthy pain-free subjects (83). In addition, genetic variations have been implicated in the pathogenesis of TMD pain; catechol-O-methyltransferase (COMT) gene variants [single-nucleotide polymorphisms (SNPs)] play a crucial role in regulating the nociceptive process in patients with TMD pain (83,89). Genetic variations in the COMT gene have been linked to pain hypersensitivity, an insufficient opioid system, anxiety, and cognitive dysfunction in TMD patients (89). Emerging evidence indicates that CS is also driven by neuroinflammation in the peripheral and central nervous systems (90). The four distinct features of neuroinflammation are activation of glial cells (microglia and astrocytes), release of proinflammatory cytokines (IL-1, IL-6, IL-1β, TNF-α, and nuclear factor-kappa B) and chemokines, migration of peripheral immune cells, and localized tissue damage (90,91). Thus, neuroinflammation may be essential to the persistence of TMD pain, and the transition from acute to chronic pain is called chronification. Sabsoob et al. demonstrated that myofascial pain was associated with a higher risk of transitioning from acute to chronic TMD pain at 6-month follow-up, and this transition risk was greater in females (92). Though depression and somatoform disorders were more common in chronic TMD patients, psychological factors did not increase the risk of transition; instead, pain intensity at baseline was associated with more intense TMD pain at a 6-month follow-up (92). Therefore, it is essential to prevent the transition of acute to chronic TMD pain by early recognition of risk factors and by a biopsychosocial multimodal approach for pain management (93).

Management strategies for TMDs

Clinicians use multimodal management strategies that include conservative non-surgical treatment options (self-care, occlusal splints, physical therapy, exercise training programs, pharmacological and cognitive-behavioral therapies) and invasive surgical treatment to treat TMDs (94). Yao et al., in a systematic review and network meta-analysis comprising 233 randomized controlled trials (RCTs), aimed to explore the comparative effectiveness of available interventions for chronic pain secondary to TMDs. They reported several conservative, pharmacological, and invasive management strategies for patients with chronic TMD pain, but the comparative effectiveness of these therapies is uncertain. However, the interventions that increase pain coping and encourage movement and activity were found to be more effective in reducing chronic TMD pain. The three interventions (cognitive behavioural therapy augmented with biofeedback or relaxation therapy, therapist-assisted jaw mobilisation, and manual trigger point therapy) were found to be probably most effective in reducing TMD pain compared to placebo/sham procedures. In contrast, moderate to high certainty evidence revealed that although five interventions that included cognitive behavioural therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, self-massage, and education) were less effective for relieving TMD pain, but were more effective than placebo and sham procedures (37).

Conservative treatment is recommended as the primary treatment option to manage TMJ pain. Among these, physiotherapy, including exercise interventions, is widely used for painful TMD conditions due to its non-invasive and cost-effective advantages (64,95). The patient can perform exercises independently at home, and physiotherapists could provide manual therapy techniques such as joint stabilization, soft-tissue release, and massage to reduce TMJ and muscle pain, reduce muscle tension around the jaw, and improve joint mobility. Shimada et al. described four types of exercise therapies, including mobilisation therapies (manual therapy, passive jaw mobilisation with oral appliances, voluntary jaw opening exercise), muscle-strengthening or resistance training exercises (isotonic jaw opening exercise and isotonic jaw closing exercise), and coordination and postural exercises (96). Several studies and literature reviews have found therapeutic exercises effective for reducing muscle and joint pain and restoring TMJ function. Dickerson et al. (95), in a systematic review, demonstrated that mobility-type exercises using passive pressure on intraoral muscles during active stretching, and mixed therapy approaches incorporating motor control, postural education, patient education on self-care, and a home exercise program, were beneficial for pain reduction in TMJ patients. In contrast, occlusal splint and mobility exercises incorporating the contract-relaxation technique for active jaw stretching showed no significant change in pain. Mixed exercise therapy approaches twice weekly were reported to be most effective for the treatment of TMJ pain. Exercise therapy provided moderate short-term and variable long-term treatment effects in the reduction of pain and improvement of range of motion in patients with TMJ dysfunction (95). Zhang et al. reported that patients with painful TMDs have reduced blood flow to the masseter muscle due to vasoconstriction caused by muscle hyperactivity, and the accumulation of byproducts could trigger pain. Mobilisation therapy applied to the TMJ stimulates parasympathetic activity, increases local blood flow to the muscles, and induces analgesia. In addition, stretching exercises also contribute to the reduction of pain intensity and to improving mandibular function; however, the effectiveness of exercise therapy was observed to be comparable to occlusal splints for painful TMDs, which requires high-quality, well-designed randomised controlled trials on larger populations to validate the efficacy of exercise programs (36). Shimada et al. suggested mobilisation therapies as a promising management option for painful TMJ conditions such as myalgia and arthralgia, but intensity and duration of exercise should be considered according to the specific TMD (96).

Chronic TMD has been associated with joint dysfunctions, such as anterior disc displacement with reduction (ADDwR) and without reduction (ADDwoR) (97). Disc displacement with reduction (DDwR) accounts for 41% of TMD clinical diagnoses and occurs in 33% of asymptomatic individuals (98). ADDwR is characterized by joint pain, clicking or popping sounds in TMJ, and disc returns to normal position on jaw opening, whereas in ADDwoR, the disc remains displaced, and joint sounds typically do not occur with limitation of mouth opening and restricted mandibular movements (99). Several treatment options, such as physical therapy, analgesics, occlusal splints, arthrocentesis, arthroscopic lysis or lavage, and disc repositioning by arthroscopy or open surgery, are available to manage anterior disc displacement (100). Still, there is limited evidence regarding the most effective approach to managing DDwoR (101). Yamaguchi et al. (29) investigated the benefits of early intervention in TMD patients; manual therapy (TMJROME) performed by the dentist and home exercise [self-traction therapy (STT)] conducted by the patient as a single exercise therapy under the supervision of the dentist were the protocol for TMJ patients with ADDwoR, and the control group received only an explanation of the pathology. Clinical symptoms, including maximum painless opening distance, pain on motion and mastication, and degree of difficulty in daily life, were evaluated in TMJ patients with ADDwoR at the first and 2-week follow-up visits and compared with the control group. For both groups, maximum painless opening distance (P=0.001) and degree of difficulty in daily life improved significantly. In the treatment group, pain on motion (P=0.001) and pain on mastication (P=0.007) increased considerably throughout the assessment period. The findings suggested that early exercise may improve outcomes in patients with ADDwoR, and it is recommended to determine the appropriate force for manual therapy (29).

Pain sensitization is common in musculoskeletal patients, causing significant disability and lower quality of life (38). Pain is a defining feature of TMDs that is aggravated by manipulation or jaw function during chewing, yawning, or clenching (1). Exercises for chronic pain conditions, including TMDs, include aerobic, isometric, and isotonic exercises, tailored to the specific needs and abilities of the patient, as responses to exercise vary and some individuals with chronic pain may experience pain exacerbation following an acute bout of exercise (102). AEs involve rhythmic, repetitive activity that uses large muscle groups and joint movements and is performed over an extended period of 20–60 minutes (42). Regular AE enhances cardiovascular health, reduces anxiety, and improves the quality of life of individuals with chronic pain conditions (103). AE influences anatomical and functional changes in individuals with pain and helps normalize abnormal brain activity that affects pain transmission (104). Previous studies have suggested that different types of AE, such as walking, stationary cycling, or stepping, involve physical exercise of low to high intensity that may reduce pain sensitivity to noxious stimuli and decrease pain perception through EIH in chronic pain conditions (16,38,105). Tan et al. found that AE involving walking or cycling, performed at a submaximal intensity but with incremental increases, for a 4–60 min duration and up to 12 weeks can produce a median (minimum, maximum) percentage improvement of 10.6% (2.2%, 24.1%) in pain sensitisation, however further research is needed to determine the improved clinical outcomes including reduced disability and greater quality of life after AEs (105). In a systematic review, de Oliveira-Souza et al. reported the positive effects of AE on pain in chronic pain conditions such as chronic neck pain, TMD, tension-type headache, and low back pain, which have similar features of abnormal pain processing in the central nervous system and CS related to nociplastic pain (16). Moleirinho-Alves et al. reported that TMD patients in the therapeutic exercise group and in the therapeutic exercise plus AE group experienced reductions in pain intensity (P<0.001) and improvements in Oral Health Impact Profile-14 scores (P<0.001) after 8–12 weeks. In the AE-only group, a reduction in pain intensity was also observed (P=0.001), although this change did not translate into improved oral health-related quality of life (P=0.55). The authors emphasized that these findings reflect the occurrence of EIH following therapeutic and AE interventions. They also highlighted the importance of considering multiple components—such as frequency, duration, type, and intensity—when designing individualized exercise programmes for patients with chronic pain (106). Tables 3,4 summarize key characteristics from recent studies on the EIH response following exercise therapy in patients with TMDs and chronic musculoskeletal pain conditions (27,38,107-112).

EIH in temporomandibular disorders

Studies have investigated the presence of EIH after high-intensity AE in healthy populations; in contrast, dysfunctional EIH and deficient pain-inhibiting are observed locally and at remote sites in most chronic pain conditions (22) (Tables 3,4). Lanefelt et al. (27) determined the effects of static contraction of the jaw-closing muscles (tooth clenching) until exhaustion on endogenous pain inhibition, both locally (masseter muscle) and remotely [brachioradialis (BR) muscle], in healthy, pain-free volunteers and in patients with chronic TMD myalgia. In their study, PPTs were recorded at the masseter and BR muscles on the right or left side at baseline by an electronic pressure algometer in healthy volunteers. In contrast, PPTs were recorded at the most painful side in the chronic TMD myalgia patients. EIH was determined by recording PPTs in the masseter and BR muscles during clenching until exhaustion. PPT was evaluated at the beginning of clenching (20 to 30 seconds after contraction onset), mid-time, end, and 10 minutes after contraction. Maximum voluntary force (MVF) was measured using a bite-force transducer on the same side as the PPT recordings. Pain intensity and fatigue were assessed before and after clenching. Pain amplification was performed by applying mechanical pressure to the masseter muscle for 2 minutes, with pain evaluated every 30 seconds. Results showed that tooth clenching until exhaustion could activate EIH locally; the magnitude of EIH was similar in women with TMD myalgia and in pain-free women with no deficient EIH. Pain intensity was higher in women with TMD (P<0.001) than in healthy pain-free women. Pain amplification was observed only in women with TMD (P<0.001), regardless of normal EIH. These results suggest a local EIH response even in chronic TMD myalgia, although the small, sex-specific sample and non-standardized testing times limit generalization. Because all TMD participants were women and the study did not control for menstrual-cycle or diurnal variations, the findings should be interpreted as preliminary evidence that preserved but imbalanced pain modulation may exist in female TMD patients. In TMD patients, static muscle contraction (clenching) triggers the release of sensitizing substances, which restrict blood flow, leading to muscle ischaemia and damage. As a result, lower baseline PPT in the masseter muscle was observed in the TMD group. Moreover, baseline PPT was also lower in the remote, pain-free BR muscle in the TMD group, indicating the involvement of central mechanisms, and women with TMD showed pain amplification at the masseter muscle on application of continuous painful pressure, which suggests the involvement of pain facilitatory and descending mechanisms in driving nociceptive pain despite the normal EIH. Furthermore, gender differences in EIH and pain sensitivity were observed in Lanefelt et al.’s study; pain-free women had less effective pain inhibition than men during contraction of the masseter and BR muscles, attributed to less efficient CPM in women. MVF during clenching of the teeth and fist was higher in men compared to women. Higher pressure was used to evoke pain in men, as higher pain sensitivity to continuous painful pressure was observed in men [corresponding to 64/100 on the visual analogue scale (VAS)] than women (corresponding to 55/100 on the VAS) (27).

Myofascial pain is characterized by localized hyperirritable taut bands of skeletal muscle known as myofascial trigger points, which are induced by peripheral and CS and systemic inflammation. Therefore, the goal of intervention for myofascial pain is to increase blood flow to the trigger point, thereby reducing pain and inflammation. AE can reduce trigger points by increasing blood flow and oxygen saturation, allowing more blood and metabolic substrates to enter the myofascial trigger point. AEs may modulate CS mechanisms, increase PPTs in muscle tissue, and induce EIH. Regular AE might enhance endogenous pain-inhibitory capacity and reduce pain sensitivity by increasing the release of serotonin, opioids, catecholamines, endocannabinoids, and endomorphins in central pathways involved in nociception modulation, thereby inducing hypoalgesia (42). In a systematic review, Ahmed et al. reported that AE in fibromyalgia patients reduced circulating levels of proinflammatory cytokines (IL-6 and IL-8) to normal levels and reduced substance P compared with strengthening exercises (113). Similarly, AEs combined with muscle-strengthening and stretching could be more beneficial for managing myofascial pain syndrome (MPS) and chronic pain conditions. Patients with myogenic TMD tend to present with low PPT at local and remote areas, due to the presence of widespread peripheral sensitisation. AEs are a useful therapeutic strategy to treat widespread peripheral sensitization in myogenic TMD patients. These exercises increase blood flow, allowing mechanical reorganization of muscle fibres and decreasing peripheral sensitization. Dantony et al. evaluated the efficacy of AEs on widespread peripheral sensitization in patients with myogenic TMD. TMD patients were divided into two groups: a control group that received physical therapy comprising education, manual therapy (distraction of the TMJ, mobilisation of the occipital atlas segment, manual pressure), and therapeutic exercises (opening and closing of TMJ, isometrics, deep cervical muscle training), and each physical therapy session lasted for 30 minutes. The second group received physical therapy and performed high-intensity interval AE on a stationary bike. Both groups completed six sessions over four weeks; the primary outcome, PPT of the Achilles tendon, and the secondary outcome, the CS inventory (CSI), were recorded at baseline (T0), post-intervention (T1), and after 12 weeks (T3). Significant differences were observed between the groups, favouring the AE plus physical therapy group at T1 and T2 for the left Achilles PPT (T1, P<0.01; T2, P<0.001) and CSI (T1, P<0.001; T2, P<0.01), and at T2 for the right Achilles PPT (P<0.001). The findings suggested that incorporating AE into physical therapy may be associated with improvements in widespread sensitization among myogenic TMD patients; however, the small sample size limits the generalizability of the results. Further studies are warranted to confirm the durability and magnitude of these effects, particularly in arthrogenic TMD populations (38).

Xu et al. reported that different resistance exercises, including proprioceptive neuromuscular facilitation (PNF), isotonic, and isometric exercises, may have local and global effects on EIH in patients with MPS. This may be due to altered endogenous pain modulation (110). MPS can progress to CS, characterized by pain hypersensitivity, due to disruption of the balance between descending facilitatory and inhibitory systems, which may attenuate the EIH response. However, regarding endogenous pain modulation, it has been postulated that sensory input during exercise, particularly proprioception and C fibres, can influence the EIH response. PNF exercises can increase C-fibre and proprioceptive inputs, thereby positively affecting EIH in patients with chronic pain, including MPS. Therefore, it is important to evaluate and compare the impact of various resistance exercises on EIH in MPS patients. In an RCT by Xu et al., PNF exercise had a more significant analgesic effect on MPS after intervention (P=0.01) compared with the control group and other exercises, due to enhanced proprioception and C-fibre inputs from additional eccentric and dynamic muscle contractions. PNF (P<0.001) and isotonic exercise (P=0.02) produced the most significant change in PPT at the trigger point compared to controls, suggesting the onset of hypoalgesia during the CPM test. The CPM test provides a cold stimulus that can activate the C-fibre afferent and descending pain-inhibition system, which may overlap with EIH response. The findings showed that PNF and isotonic exercises positively affected CPM responses in MPS patients and elicited EIH at trigger-point, arm, and leg sites. Thus, exercise with optimal intensity and type could affect endogenous pain modulation, and various resistance exercises may enhance descending inhibition and reduce pain by activating endocannabinoids, endogenous opioids, and the 5-hydroxytryptamine (5-HT) system. Isometric exercise showed the opposite effect, with no significant positive impact on EIH in MPS patients compared with PNF. Isotonic exercises (114), which are consistent with the Staud et al. study, in which isometric exercises increased pain sensitivity in fibromyalgia patients, may be due to altered central pain mechanisms, abnormal descending inhibition, or excessive activation of muscle nociceptive afferents (115).

The association of TMDs with cervical spine disorders, particularly neck pain, has been widely recognized (114). Investigators have found that tender points are common in TMD patients, and neck pain is associated with TMD in 70% of cases (42,114). A significant correlation was observed between jaw and neck disability (P=0.08); thus, TMD patients experience more pain during neck movements than asymptomatic individuals (116). Subjects with myogenic TMDs typically exhibit greater masticatory and cervical muscle sensitivity, self-reported neck disability, and reduced pressure-pain thresholds in the anterior temporalis, sternocleidomastoid, and upper trapezius muscles. de Oliveira-Souza et al. [2024] demonstrated that an 8-week neck-motor-control training program significantly improved orofacial pain intensity, jaw function, and oral-health-related quality of life in women with chronic TMD involving the neck (117). Thus, exercise interventions targeting the cervical muscles could also benefit patients with TMDs. However, it is important to determine the exercise parameters capable of producing the most substantial hypoalgesic effects, which can help select a suitable exercise intervention for patients with chronic TMD pain. Tavares et al. designed the protocol to elucidate the positive effects of neck motor control and AEs on EIH in individuals with TMDs and neck pain. Participants with neck pain and/or TMD will be randomized into neck motor control and AE training groups. They will be assessed before, immediately after, and 15 minutes after three treatment sessions within a 12-week exercise programme. Pain intensity, PPTs, tolerance of masticatory and neck muscles, and self-perception of improvement will be measured using the Global Rating of Change Scale, and EIH response will be recorded. Thus, assessing patients’ perceptions of changes after treatment and tailoring the intervention based on EIH responses can improve clinical outcomes and adherence to the exercise training programme (42).

Clinical implications and future recommendations

Effective exercise prescription for patients with temporomandibular disorders should be individualized according to pain severity, psychosocial profile, and baseline physical capacity. A gradual, low-to-moderate-intensity approach is recommended to minimize symptom flares and improve tolerance. Monitoring pressure-pain thresholds before and after exercise and considering indicators of CPM or TSP may help clinicians adjust intensity and frequency appropriately. To enhance adherence, exercise programs should integrate patient education, pacing strategies, relaxation or breathing components, and regular feedback or follow-up. Choice of aerobic, isometric, or resistance exercise can be guided by patient preference, comorbid musculoskeletal involvement, and overall treatment goals, ideally in combination with standard conservative measures such as manual therapy and self-care education.

Exercise interventions are considered a preferable, non-invasive, and cost-effective adjunct therapy to conservative or surgical treatment options for the management of TMD patients (16,113). Various exercises, such as aerobic, isometric, and isotonic, have been shown to produce hypoalgesia and reduce pain intensity in patients with chronic musculoskeletal pain and myogenic TMD (16,42). Moderate intensity AE performed for more than ten minutes is capable of reducing pain perception, possibly by activation of endogenous mechanisms of pain control and modulation; therefore, various AEs such as cycling, running, hiking, swimming, and walking could be a beneficial therapeutic option for patients with chronic orofacial and musculoskeletal pain conditions (16). Adding AEs to other management strategies, such as strengthening exercises and manual therapy, could reduce the pain intensity and health-related quality of life in subjects with chronic pain. Geneen et al. concluded that the quality of evidence about the effects of physical activity and exercise on chronic pain is low (118). Exercise had a small to moderate impact on reducing pain severity and improving physical function, and produced variable effects on psychological function and quality of life. In TMD patients, a single bout of exercise has been found to exacerbate the pain and lower the pain threshold in chronic TMD pain patients. In contrast, regular exercise has been shown to effectively reduce the severity of chronic TMD pain by activating the endogenous pain-inhibitory system. Furthermore, widespread peripheral sensitization in remote areas is present in myogenic TMD patients; therefore, in addition to usual standard treatment and physical therapy, myogenic TMDs should include exercise training programmes (38). In a Lanefelt et al. study, the magnitude of EIH in the contracting masseter muscle was similar between women with TMD myalgia and pain-free women during isometric muscle contractions (tooth clenching), without deficient EIH in women with TMD myalgia (27). However, no definitive conclusions could be drawn from the previously published studies about the effects of single-session exercise on EIH in TMD patients; therefore, to address the evidence gap, more RCTs and experimental studies should be conducted to understand the underlying biological mechanisms and the presence of EIH in TMD patients following the single bout of exercise.

Strengths and limitations

The strength of this review is that we compiled evidence on the EIH response to exercise in pain-free individuals and in individuals with chronic pain conditions, including TMD. Another strength is that we have identified several possible biological mechanisms that may reduce pain sensitivity and lead to EIH in TMD patients, and we have emphasized the effects of different types of exercise, with a focus on exercise intensity and duration in chronic pain. The impact of regular physical activity and exercise on the TMD population in local and remote sites have been discussed through the findings reported in the studies. The limitation was in the extraction of high-quality evidence, particularly about the effect of different exercise interventions in TMDs, and there was heterogeneity in outcome measures (pain intensity, pain tolerance, PPT, and EIH response), including the variations in EIH response to a single session of exercise in both pain-free and chronic pain populations. The inclusion of lower-level evidence and the restriction to English-language studies may also introduce bias and limit the generalizability of the findings. Although some studies reported moderate to large effect sizes, many did not provide effect estimates, which limits the ability to judge the clinical magnitude of observed changes (107-109).

Conclusions

Emerging evidence indicates that exercise can modulate pain sensitivity and contribute to hypoalgesia in individuals with temporomandibular disorders. Nevertheless, variability in study design, exercise protocols, and outcome measures, together with the limited number of rigorously conducted trials, constrains definitive conclusions regarding clinical efficacy. Future research should prioritize the development of standardized outcome frameworks, direct comparisons between aerobic, isometric, and isotonic regimens, and mechanistic investigations incorporating CPM and endocannabinoid biomarkers. Advancing these research directions will be essential to elucidate the pathways mediating EIH and to establish optimized, evidence-based exercise prescriptions for chronic TMD pain management.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Mythili Kalladka & Ming Xia) for the series “Current Status and Latest Research Progress in the Pain Management of Temporomandibular Disorders (TMDs)” published in Journal of Oral and Maxillofacial Anesthesia. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://joma.amegroups.com/article/view/10.21037/joma-25-14/rc

Peer Review File: Available at https://joma.amegroups.com/article/view/10.21037/joma-25-14/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-25-14/coif). The series “Current Status and Latest Research Progress in the Pain Management of Temporomandibular Disorders (TMDs)” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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