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Pain tolerance

Pain tolerance refers to the maximum intensity or duration of a painful stimulus that an individual is able or willing to endure before it becomes intolerable.^[1] It is distinct from pain threshold, which is the minimum stimulus intensity perceived as painful, as tolerance reflects a voluntary endpoint influenced by psychological and physiological factors rather than an automatic sensory response.^[2] This psychobiological construct plays a key role in how people respond to acute and chronic pain, varying widely among individuals due to a complex interplay of genetic, demographic, and environmental influences.^[3] Pain tolerance is commonly assessed in experimental settings using methods like the cold pressor test, where participants immerse their hand in ice water and indicate when the pain exceeds their endurance limit, providing a quantifiable measure of tolerance duration.^[4] Other techniques include thermal heat stimulation or pressure algometry, which gauge the highest tolerable level of heat or pressure applied to the skin.^[5] These standardized procedures help researchers distinguish tolerance from mere perception, revealing that tolerance often decreases with repeated exposure in some contexts while potentially increasing through conditioning or cognitive strategies.^[6] Numerous factors modulate pain tolerance, including biological elements such as genetics, which can account for up to 60% of variability in pain responses, including through polymorphisms in genes like COMT and OPRM1.^[7] Demographic variables also contribute: women generally exhibit lower tolerance than men, possibly due to hormonal differences and sex-related expectations,^[8] while older age is associated with higher pain thresholds but reduced pain tolerance.^[9] Ethnic differences further influence tolerance, with studies showing African Americans reporting lower thresholds and tolerance compared to non-Hispanic whites, linked to both genetic and socio-cultural factors.^[10] Psychosocial elements profoundly affect pain tolerance, with negative affect, anxiety, and pain catastrophizing—characterized by exaggerated negative thoughts about pain—predicting decreased endurance.^[11] Conversely, positive coping mechanisms, such as optimism or social support, can enhance tolerance by altering pain appraisal and emotional processing.^[12] In clinical contexts, low pain tolerance is a risk factor for chronic pain disorders, opioid misuse, and poorer outcomes in conditions like fibromyalgia or postoperative recovery, underscoring its relevance to pain management strategies.^[13]

Definition and Fundamentals

Definition and Conceptual Overview

Pain tolerance refers to the maximum intensity of a noxious stimulus that an individual is willing to endure before the sensation becomes intolerable, marking a subjective endpoint where pain shifts from bearable to overwhelming. This concept is often quantified in experimental settings using self-report scales, such as the visual analog scale (VAS), where participants mark their perceived pain intensity on a continuous line from "no pain" to "worst imaginable pain," or the numeric rating scale (NRS), which assigns a number from 0 to 10 to the pain experience.^[14] Unlike pain threshold, which denotes the initial onset of pain perception, tolerance represents the upper limit of endurance.^[15] A core aspect of pain tolerance is its high degree of individual variability, with tolerance levels differing markedly among people due to multifactorial influences, though it remains fundamentally distinct from nociception—the physiological process by which nociceptors detect and transmit signals of potentially harmful stimuli via neural pathways.^[16] Nociception provides the sensory input for pain, but tolerance involves the subjective appraisal and endurance of that input, highlighting pain as a complex psychobiological phenomenon rather than a purely reflexive response.^[17] The notion of pain tolerance traces its origins to 19th-century psychophysics, where early experimental psychologists began quantifying sensory limits, including the endurance of painful stimuli, as part of broader efforts to measure perceptual thresholds.^[18] It gained formal conceptualization in 20th-century pain research, particularly through Ronald Melzack and Patrick Wall's gate control theory of 1965, which posited that pain perception—and by extension, tolerance—is modulated by a spinal "gate" mechanism influenced by psychological factors like attention and emotion, overlaying physiological signals with central nervous system processing. This theory shifted understanding from a simplistic stimulus-response model to one emphasizing tolerance as a dynamic interplay between bodily sensation and mental state.^[19] Note that while widely used in research, pain tolerance lacks a formal definition in major pain terminology standards, such as those from the International Association for the Study of Pain (IASP).^[20]

Distinction from Pain Threshold and Intensity

Pain threshold refers to the minimum intensity of a stimulus that is perceived as painful by an individual, and it is often measured using standardized methods such as thermal heat application or mechanical pressure to determine the point at which sensation transitions to pain perception.^[21] This measure is relatively consistent within a given stimulus modality across individuals but can vary based on factors like the testing site and stimulus type.^[21] In contrast, pain intensity describes the subjective magnitude or strength of the ongoing pain experience, typically assessed through self-report scales such as the Numeric Rating Scale (NRS) or Visual Analog Scale (VAS), where individuals rate their pain from 0 (no pain) to 10 (worst possible pain).^[14] Unlike threshold, which marks the onset of pain detection, intensity captures the perceived severity during sustained exposure and is not fixed as an endpoint but rather a dynamic rating that can fluctuate.^[14] Pain tolerance differs from both threshold and intensity by representing the maximum level of pain an individual is willing or able to endure before seeking relief or withdrawing from the stimulus, often tested by extending exposure until the participant signals cessation. For instance, a person might first perceive pain at a low intensity (marking their threshold) but tolerate it up to a much higher level before stopping, illustrating tolerance as an upper endurance limit rather than initial detection or momentary rating. Research indicates that threshold and tolerance are distinct constructs with low to moderate correlations across modalities, meaning sensitivity to pain onset does not reliably predict endurance capacity.^[22] These distinctions are critical in pain research and clinical practice, as conflating threshold with tolerance can lead to inaccurate assessments of pain coping abilities, potentially resulting in inappropriate treatment strategies that overlook individual differences in endurance versus detection.

Historical Development of the Concept

The concept of pain tolerance, referring to the maximum level of pain an individual can endure, has roots in ancient observations of variations in human endurance to painful stimuli. The Hippocratic Corpus, compiled around 400 BCE, includes references to pain as a clinical variable with detailed descriptors for location and duration, laying early groundwork for recognizing differences in pain experience.^[23] Medieval accounts, particularly in the context of judicial torture during the Inquisition from the 13th to 15th centuries, further documented disparities in pain endurance; inquisitorial records described how some individuals confessed rapidly under duress while others withstood prolonged agony, influencing legal assessments of reliability in testimony.^[24] The modern scientific study of pain tolerance emerged in the 19th and early 20th centuries within experimental psychology, with systematic quantification beginning in the 1940s and 1950s through the development of the dolorimeter by James D. Hardy, Harold G. Wolff, and Helen Goodell at Cornell University. Their studies used radiant heat to measure not only pain thresholds but also tolerance levels, establishing reproducible methods to assess how subjects sustained painful stimuli before withdrawal, which shifted the focus from anecdotal reports to empirical data.^[25] A pivotal contribution came from Henry K. Beecher's observations during World War II, detailed in his 1946 analysis of wounded soldiers at Anzio, where he found that only 25% requested analgesics despite severe injuries—far lower than civilian rates—attributing this elevated tolerance to motivational factors like the meaning of wounds in combat, thus highlighting psychological influences on pain endurance.^[26] By the late 20th century, the concept integrated into formalized frameworks, with the International Association for the Study of Pain (IASP) adopting its inaugural definition of pain in 1979, which implicitly encompassed tolerance by emphasizing the subjective sensory and emotional dimensions of pain experience.^[20] In the late 1980s and 1990s, early neuroimaging studies using positron emission tomography (PET) began linking pain modulation, including aspects of sustained perception related to tolerance, to specific brain regions such as the anterior cingulate cortex.^[27] This era marked a broader evolution from predominantly physiological perspectives to the biopsychosocial model, proposed by George L. Engel in 1977 and increasingly applied to pain research post-1970s, which incorporated biological, psychological, and social elements in understanding tolerance variations.^[28]

Biological and Physiological Factors

Genetic and Neurobiological Influences

Genetic factors play a significant role in individual differences in pain tolerance, with variations in specific genes influencing pain modulation pathways. Polymorphisms in the COMT gene, which encodes catechol-O-methyltransferase—an enzyme involved in the degradation of catecholamines such as dopamine—have been linked to variations in pain sensitivity and tolerance. For instance, certain haplotypes of the COMT gene, designated as low pain sensitivity (LPS), high pain sensitivity (HPS), and average pain sensitivity (APS), result in differing enzymatic activity levels that affect prefrontal dopamine clearance and, consequently, pain processing; individuals with the LPS haplotype exhibit higher tolerance to experimental pain stimuli compared to those with HPS.^[29] Polymorphisms in the OPRM1 gene, encoding the mu-opioid receptor, also influence pain tolerance. The A118G single nucleotide polymorphism (SNP) in OPRM1 has been associated with altered pain sensitivity and opioid responsiveness, with the G allele linked to higher pain thresholds and tolerance in some experimental pain models.^[30] Mutations in the SCN9A gene, which encodes the voltage-gated sodium channel Nav1.7 expressed in nociceptive neurons, can lead to extreme pain tolerance or insensitivity. Biallelic loss-of-function mutations in SCN9A cause congenital insensitivity to pain (CIP), a rare autosomal recessive disorder characterized by the complete inability to perceive physical pain, often resulting in unrecognized injuries during childhood.^[31]^[32] Heritability estimates from twin studies indicate that genetic factors contribute substantially to pain tolerance, with variance explained ranging from 20% to 50% depending on the pain modality and population studied. These estimates derive from comparisons of monozygotic and dizygotic twins, highlighting a moderate to strong genetic influence on evoked pain phenotypes such as thermal or pressure pain tolerance.^[33] Neurobiological mechanisms underlying pain tolerance involve intricate neural circuits and neurotransmitter systems that modulate nociceptive signaling. Endogenous opioids, released from sites like the periaqueductal gray (PAG), activate descending inhibitory pathways to suppress pain transmission at the spinal level by binding to mu-opioid receptors on dorsal horn neurons.^[34] Serotonin (5-HT) pathways, originating from raphe nuclei and projecting via the PAG-rostral ventromedial medulla (RVM) axis, further contribute to this inhibition by enhancing presynaptic inhibition of excitatory neurotransmitters in the spinal cord.^[35] Functional magnetic resonance imaging (fMRI) studies reveal the prefrontal cortex's involvement in modulating pain tolerance limits through cognitive and emotional integration. Activation in the dorsolateral and anterolateral prefrontal cortex during pain anticipation or reappraisal tasks correlates with increased tolerance, as this region engages descending controls to dampen nociceptive activity in subcortical structures like the thalamus and PAG.^[36]^[37]

Age, Sex, and Hormonal Variations

Pain tolerance exhibits notable variations across the lifespan, influenced by physiological changes in neural processing and overall health. In pediatric populations, children often demonstrate higher pain sensitivity compared to adults, with lower thresholds and tolerance levels in experimental settings, though relative tolerance may appear elevated in contexts adjusted for developmental differences in pain reporting and processing. As individuals progress into young adulthood (approximately 20-40 years), pain tolerance typically peaks, reflecting optimal neural plasticity and fewer comorbidities that could exacerbate pain perception.^[38]^[39]^[40] With advancing age, particularly beyond 60 years, pain tolerance tends to decline slightly, despite an increase in pain thresholds that indicates reduced sensitivity to initial noxious stimuli. This decline is attributed to diminished neural plasticity in pain-modulating pathways and the accumulation of comorbidities such as arthritis and neuropathy, which amplify overall pain experience and reduce endurance. Meta-analyses confirm that while thresholds rise progressively with age—showing large effect sizes between younger and older groups—tolerance remains largely stable until late adulthood, when subtle reductions emerge due to these age-related factors.^[41]^[42]^[43]^[40] Sex differences in pain tolerance are well-documented, with females generally exhibiting lower tolerance than males in experimental paradigms, as evidenced by meta-analyses reporting moderate effect sizes (Cohen's d ≈ 0.57). These disparities are consistent across various stimuli, such as thermal and pressure pain, and persist even after controlling for psychological factors, though the gaps are small in magnitude. Hormonal fluctuations contribute significantly, with estrogen variations in females linked to cyclical changes; tolerance is often reduced during the luteal and menstrual phases, when pain ratings are higher due to elevated progesterone and lower estrogen levels relative to the follicular phase.^[44]^[44]^[45]^[46] In males, higher testosterone levels are associated with enhanced pain tolerance, as demonstrated in studies showing positive correlations between endogenous testosterone and pain thresholds, potentially through modulation of opioid and enkephalin systems. Exogenous testosterone administration further supports this, improving tolerance in hypogonadal individuals with chronic pain. Cortisol, as a key stress hormone, plays a bidirectional role in pain modulation; acute elevations during stress can decrease tolerance by heightening sensitivity, with negative correlations observed between cortisol levels and pain thresholds in both sexes.^[47]^[48]^[49]^[50]^[49] Longitudinal cohort studies, including analyses from the UK Biobank, highlight how hormonal profiles contribute to variability in pain tolerance over time, with declining gonadal hormones in aging populations linked to increased chronic pain prevalence and reduced tolerance, particularly in women during menopause. These findings underscore the interplay of age, sex, and hormones in shaping pain responses across the lifespan.^[51]^[52]

Early Life and Neonatal Experiences

Early life experiences, particularly neonatal injuries and procedural pains, significantly influence the development of pain tolerance through programming of neural and stress response systems. Preterm infants in neonatal intensive care units (NICUs) often endure hundreds of painful procedures, such as heel sticks for blood sampling, which can lead to heightened pain sensitivity persisting into childhood and adolescence. For instance, very preterm infants exposed to repeated heel sticks demonstrate altered pain reactivity, including both hypersensitivity to acute stimuli like brief heat and hyposensitivity to prolonged heat, as observed in school-aged children.^[53] In animal models, neonatal pain in rat pups induces central sensitization, characterized by long-term enhancements in spinal nociceptive processing and reduced thresholds to thermal and mechanical stimuli in adulthood.^[54] The programming hypothesis posits that early pain experiences alter the hypothalamic-pituitary-adrenal (HPA) axis, resulting in dysregulated stress responses and diminished pain tolerance later in life. In human cohorts of NICU survivors, greater cumulative neonatal procedural pain correlates with blunted cortisol responses during stress challenges at 8 months corrected age and altered reactivity into school age, suggesting enduring HPA axis reprogramming.^[53] This programming contributes to lower pain tolerance by sensitizing pain pathways and impairing adaptive coping mechanisms, with evidence from longitudinal studies of preterm infants showing associations between early pain exposure and increased pain sensitivity in adolescence.^[55] Epigenetic modifications provide a mechanistic link between neonatal trauma and long-term pain outcomes, with early pain inducing DNA methylation changes in genes involved in pain and stress regulation. For example, pain-related stress in preterm infants is associated with increased methylation of the serotonin transporter gene (SLC6A4), which persists at 3 months and may influence emotional and sensory pain processing.^[56] In rat models, repetitive neonatal pain elevates DNA methylation of the mu-opioid receptor gene (Mor-1) in the spinal cord, correlating with heightened nociceptive responses in adulthood. These changes are potentially reversible through supportive interventions; kangaroo care (skin-to-skin contact) during procedures reduces immediate pain responses in preterm neonates and may mitigate long-term programming by stabilizing HPA axis function and limiting epigenetic alterations.^[57] Specific neonatal procedures, such as circumcision and vaccinations, exemplify how early pain can reduce adult pain tolerance. Neonatal circumcision without adequate analgesia heightens pain responses to subsequent immunizations in infancy and is linked to altered socio-affective pain processing in adulthood, including increased emotional reactivity to pain.^[58] Similarly, unmitigated pain from routine vaccinations in infancy correlates with heightened pain responses at later vaccinations in early infancy (up to 6 months), supporting the role of procedural pain in programming neural hypersensitivity during sensitive developmental periods.^[59]

Psychological and Cognitive Factors

Mental Health Conditions and Coping Mechanisms

Mental health conditions significantly influence pain tolerance through emotional and cognitive pathways, often amplifying negative affect that heightens pain perception and reduces endurance. Depression and anxiety are associated with lowered pain tolerance, as induced negative emotions like these lead to decreased ability to withstand experimental pain stimuli, such as pressure tasks, compared to neutral states.^[60] This effect stems from amplified negative affect, which exacerbates pain reports and shortens tolerance duration in affected individuals.^[61] Pain catastrophizing, a cognitive pattern involving rumination, magnification, and helplessness, serves as a key predictor of reduced pain tolerance, as measured by the Pain Catastrophizing Scale developed by Sullivan et al.^[62] Coping mechanisms play a pivotal role in modulating pain tolerance, with active strategies generally enhancing endurance while passive ones diminish it. Active coping, such as problem-solving or distraction, correlates with improved pain adjustment and higher tolerance levels by fostering perceived control over pain experiences.^[63] In contrast, passive avoidance, including catastrophizing or withdrawal, is linked to decreased tolerance and poorer pain outcomes, as it reinforces threat appraisals that heighten sensitivity.^[64] Mindfulness-based interventions exemplify effective coping, demonstrating increases in pain endurance in cold pressor tests through enhanced present-moment awareness and reduced emotional reactivity.^[65] Specific psychiatric disorders exhibit distinct impacts on pain tolerance tied to their core symptoms, though findings are mixed. Post-traumatic stress disorder (PTSD) is associated with altered pain sensitivity, including potentially lower sensitivity and longer tolerance times in some experimental tasks compared to healthy controls, possibly due to dissociation rather than hypervigilance.^[66] Schizophrenia shows no overall differences in pain sensitivity compared to controls, with hypersensitivity to mechanical stimuli in subgroup analyses, contrary to earlier reports of hyposensitivity; ongoing research explores perceptual alterations.^[67] These patterns highlight debates in how emotional dysregulation and perceptual changes affect pain processing. Therapeutic interventions targeting these mental health factors can enhance pain tolerance effectively. Cognitive-behavioral therapy (CBT) protocols, which address maladaptive thoughts and promote adaptive coping, have been shown to improve pain management and increase tolerance in chronic pain patients by altering emotional responses to pain signals.^[68] For instance, CBT reduces pain interference and catastrophizing, leading to greater endurance in daily functioning and experimental settings.^[69]

Attention, Expectation, and Association Techniques

Attention diversion techniques involve redirecting cognitive focus away from painful stimuli to mitigate perceived pain intensity and enhance tolerance. In laboratory settings, tasks such as counting backward from 100 by sevens have been shown to increase pain tolerance during thermal or pressure pain tests, as measured by prolonged endurance times before reporting intolerable pain. Neuroimaging studies corroborate this effect, revealing reduced activation in the insula—a brain region associated with pain perception—during distraction, suggesting that attentional shifts compete for neural resources otherwise devoted to pain processing. Expectation plays a pivotal role in modulating pain tolerance through anticipatory mechanisms, where beliefs about impending pain can either amplify or attenuate the experience. Placebo analgesia, for instance, leverages positive expectations to boost tolerance, effectively reversing nocebo effects (negative expectations that heighten pain) in controlled trials using heat pain paradigms. Seminal work by Wager et al. (2004) demonstrated that anticipated pain relief activates prefrontal and rostral anterior cingulate cortices, which in turn downregulate nociceptive signaling in the spinal cord, thereby extending tolerance durations in functional MRI-monitored experiments. Association and dissociation represent contrasting cognitive strategies for managing pain, rooted in perceptual control frameworks. Association techniques encourage focused attention on the pain sensation itself—such as athletes mentally tracking bodily signals during exertion—to foster long-term tolerance by promoting adaptive coping and reducing fear-avoidance behaviors, as outlined in Melzack and Wall's gate control theory of pain (1965), which posits that selective attention can "gate" sensory inputs at the spinal level.^[70] In contrast, dissociation involves mentally escaping the pain through imagery or mental travel to neutral or pleasant scenarios, providing short-term relief by disengaging from the immediate experience; this approach has been effective in clinical settings for acute pain, increasing tolerance in electromyographic biofeedback studies. Experimental evidence further validates these techniques, particularly through virtual reality (VR) distraction trials. In cold pressor tests—where participants immerse hands in ice water—VR interventions, such as immersive games or scenic environments, have significantly enhanced pain endurance compared to non-VR controls, with participants reporting lower subjective pain ratings and sustained submersion times.^[71] These findings underscore the practical utility of attention, expectation, and association methods in both research and therapeutic contexts, building on broader psychological coping mechanisms without delving into underlying mental health conditions.

Handedness and Perceptual Biases

Handedness influences pain tolerance through brain lateralization, with right-handers typically exhibiting lower pressure pain thresholds (higher sensitivity) in the non-dominant left hand compared to the dominant right hand, reflecting hemispheric specialization in sensory processing. This asymmetry arises from differences in how the brain's hemispheres handle nociceptive signals, where the right hemisphere may process pain from the left side with greater intensity due to contralateral dominance in somatosensory pathways. Studies using automated algometers on the third digits have demonstrated this effect in right-handed individuals, while left-handers show no such lateral bias; however, literature on handedness effects is mixed, with some reports of no differences or opposite patterns.^[72] Perceptual biases in pain perception are linked to hemispheric asymmetries, particularly the left hemisphere's dominance in processing positive affect, which can facilitate greater pain tolerance by counteracting negative emotional responses to nociception. The left prefrontal cortex, associated with approach-oriented emotions and resilience, may modulate pain signals from the right side of the body, enhancing overall endurance during sustained stimuli. Split-brain studies, including those on patients with callosal sectioning, indicate the corpus callosum's critical role in interhemispheric transfer of pain information, as unilateral stimuli elicit reduced or altered perceptions ipsilaterally without intact callosal connections, underscoring how disconnection impairs balanced sensory integration.^[73] Experimental evidence from pressure pain tests reveals asymmetries related to dominance, with mixed findings on which hand shows lower tolerance; ongoing research suggests attentional and motor factors may contribute, but no consistent quantitative differences like 200-300 kPa are established across studies. This pattern holds across multiple sessions, suggesting an innate perceptual skew rather than temporary factors.^[72] Clinically, these asymmetries have implications for unilateral pain therapies, such as targeted injections or nerve blocks, where handedness assessment may optimize efficacy, though evidence is preliminary due to inconsistent findings. For instance, in procedures involving the upper limbs, considering dominance could inform personalized protocols in pain management.^[74]

Cultural and Ethnic Differences

Cultural norms significantly influence how individuals perceive, report, and tolerate pain, with collectivist societies often promoting stoic responses that result in underreporting of symptoms compared to more expressive behaviors in individualist cultures. In East Asian collectivist contexts, such as among Chinese populations, cultural emphasis on endurance and restraint leads to lower verbal expressions of pain during experimental tasks, potentially masking underlying sensitivity; however, behavioral measures like the cold pressor test often show shorter immersion times for East Asians compared to Europeans (e.g., 93 seconds vs. 116 seconds as of 2025 studies), aligning with findings of higher pain sensitivity despite stoic norms.^[75]^[76]^[77] Ethnic variations in pain tolerance have been documented in experimental settings, particularly in the United States, where African Americans often demonstrate lower thresholds and tolerance to stimuli like ischemic pain compared to non-Hispanic Whites, potentially influenced by chronic exposure to socioeconomic stressors rather than inherent differences. A seminal study involving chronic pain patients found that African American participants exhibited significantly lower ischemic pain tolerance (mean duration shorter by 35 seconds) and reported higher clinical pain severity and disability than their White counterparts. Similar patterns emerge in thermal and cold pressor tests, where African Americans show heightened sensitivity, though these findings are confounded by factors like access to healthcare. Recent research as of 2025 continues to highlight these disparities, with debates on genetic versus environmental contributions.^[10]^[78]^[79] Acculturation plays a key role in modulating these ethnic differences, as immigrants adapt pain reporting and tolerance to align with host culture norms over generations. First-generation Asian Americans, for example, display lower pain thresholds and tolerance in cold pressor tasks compared to second-generation individuals, reflecting less acculturation and higher stress from cultural transition, while second- and third-generation individuals report pain levels comparable to European Americans. Cross-cultural cold pressor data from South Asian immigrants in the UK further indicate that higher acculturation scores correlate with reduced prevalence of widespread pain, suggesting environmental adaptation influences tolerance expressions.^[76]^[80] Methodological caveats in cross-cultural pain research, including biases in self-report scales translated across languages, can exaggerate or obscure differences, as cultural idioms for pain vary and may lead to inconsistent interpretations. For instance, stoic cultural norms in collectivist groups may result in underestimation of pain intensity on Western-designed visual analog scales, while socioeconomic disparities affect participant recruitment and baseline health, necessitating standardized experimental protocols like the cold pressor test to minimize confounds. These challenges highlight the need for culturally sensitive assessment tools to accurately capture tolerance variations.^[10]^[81] Social support dynamics play a crucial role in modulating pain tolerance, with interpersonal interactions often serving as a buffer against pain through mechanisms such as empathy and affiliation. Passive support, characterized by the mere presence of others without direct intervention, has been shown to enhance pain tolerance in experimental settings. For instance, in cold pressor tasks, the presence of a friend or observer significantly increases pain threshold and tolerance compared to solitary conditions, potentially due to empathetic responses that reduce perceived pain intensity.^[82] Studies involving romantic partners further demonstrate this effect, where the simple proximity of a spouse or partner elevates pain endurance by altering sensory processing and emotional comfort, with participants exhibiting higher thresholds during pressure pain tests when accompanied.^[83] Active forms of social support, such as verbal encouragement or physical touch, provide more pronounced enhancements to pain tolerance by directly engaging affiliation motives and reducing physiological arousal. Verbal encouragement during endurance tasks, like sustained muscle contractions, has been found to improve performance and delay pain onset, with participants reporting lower perceived exertion and sustaining efforts longer than in unsupported conditions.^[84] Similarly, empathetic touch from a partner during experimental pain induction leads to measurable analgesia, where higher levels of observed empathy correlate with greater reductions in pain ratings, as evidenced in laser-evoked pain paradigms.^[85] A meta-analysis of experimental pain studies supports these findings, indicating that active social support consistently lowers pain perception and related autonomic responses across various paradigms, though effects vary by support quality and relationship closeness.^[86] Conversely, negative social dynamics, such as rejection, can exacerbate pain sensitivity by amplifying stress responses that lower tolerance thresholds. Experimental manipulations of social exclusion, using paradigms like Cyberball, result in decreased heat pain tolerance, particularly among individuals with high chronic stress, as exclusion heightens cortisol reactivity and sensitizes nociceptive pathways.^[87] This stress amplification effect underscores how interpersonal rejection transforms social pain into heightened physical vulnerability, reducing overall endurance to noxious stimuli. The effectiveness of social support often differs based on relational context, with familiar supporters like family members yielding stronger benefits than strangers in clinical and laboratory trials. In pain induction experiments, tolerance is notably higher with family observers compared to strangers, attributed to greater perceived empathy and security in familial bonds, as seen in cold pressor and pressure algometry tasks.^[88] Clinical trials involving chronic pain patients similarly show that spousal or familial support during procedures enhances endurance more than neutral stranger presence, highlighting relational familiarity as a key modulator.^[89]

Environmental and Contextual Modifiers

Environmental stressors such as noise and elevated ambient temperatures can significantly impair pain tolerance by heightening sensory sensitivity and perceived intensity. Exposure to loud noise bursts has been shown to induce hyperalgesia in men, reducing pain thresholds through surprise-related mechanisms, while producing hypoalgesia in women via fear conditioning.^[90] Similarly, acute exposure to warmer ambient temperatures, such as 30°C or 35°C, results in marked decreases in pain thresholds compared to neutral conditions at 24°C, likely due to enhanced thermal sensitivity and vasodilation.^[91] In contrast, optimal environmental conditions like exposure to bright natural lighting can enhance pain control; for instance, hospital rooms with 46% more natural light led to 22% less analgesic medication use and lower reported pain levels among postoperative patients.^[92] Contextual demands in high-stakes situations often elevate pain tolerance through stress-induced analgesia mediated by adrenaline and endogenous opioid release. Acute psychological stress, such as that encountered in threatening or performance-demanding scenarios, can temporarily suppress pain perception, allowing individuals to endure noxious stimuli longer despite the arousal.^[93] Conversely, relaxation-oriented environments, including those incorporating calming sensory cues, lower perceived pain limits by reducing hypervigilance and physiological arousal; relaxation techniques have demonstrated modest reductions in acute pain intensity across multiple studies.^[94] Sensory overload, particularly from multisensory pain stimuli, decreases endurance compared to isolated modalities by amplifying central sensitization and overall perceptual load. Individuals with heightened multisensory sensitivity exhibit greater static and dynamic pain responses, with combined thermal and mechanical stimuli exacerbating hyperalgesia more than single-modality exposure.^[95] Field studies on workplace ergonomics further illustrate these effects, showing that poor ergonomic setups, such as non-adjustable workstations, are positively associated with chronic musculoskeletal pain prevalence and reduced tolerance in office workers, with interventions like participatory redesign lowering pain reports by up to 25% in targeted groups.^[96]^[97]

Conditioning and Modulation

Habituation Through Repeated Exposure

Habituation through repeated exposure to pain involves a progressive decrease in the behavioral and neural response to a consistent nociceptive stimulus, allowing the body to adapt to predictable pain without escalating distress. This process is a basic form of non-associative learning observed across species, where repeated stimulation leads to reduced sensitivity in sensory pathways, helping to conserve energy and prevent overload from non-threatening inputs. In animal models, such as rats, this adaptation occurs independently of opioid signaling, with studies showing spinal cord dorsal horn neurons exhibiting reduced firing rates to repeated thermal or mechanical stimuli through local synaptic modifications.^[98] Human studies provide robust evidence for habituation via repeated exposure, particularly using the cold pressor test, where individuals immerse their hand in ice-cold water. In one study of healthy young men, daily cold pressor sessions over seven days resulted in significant increases in pain tolerance, with tolerance time rising by more than 100% in the dominant hand (from baseline to day 7, p < 0.05) and even greater in the nondominant hand, demonstrating progressive adaptation without external aids.^[99] This habituation is thought to stem from neural adaptations in the spinal cord and brain, including downregulation of NMDA receptor activity, which reduces excitatory signaling and prevents amplification of pain signals. However, limits exist; prolonged or intense exposure can reverse habituation into sensitization, where pain responses intensify, as seen in thermal pain experiments where high-temperature repetitions (48–49°C) led to heightened ratings instead of reduction.^[100] These mechanisms have practical applications in exposure therapy for phobias involving pain, such as needle phobia or dental anxiety, where gradual, controlled repetition desensitizes patients to anticipated discomfort. In chronic pain contexts with elevated pain-related fear, in vivo exposure systematically builds tolerance by confronting feared activities, reducing avoidance and improving function without pharmacological intervention.^[101]

Training and Behavioral Interventions

Behavioral training programs, such as progressive muscle relaxation (PMR), have been shown to enhance pain tolerance by teaching individuals to systematically tense and release muscle groups, promoting physical and mental relaxation that modulates nociceptive responses. In a study involving athletes trained in PMR with a warning cue prior to pain exposure, participants demonstrated significantly greater pain tolerance compared to controls, as measured by endurance on a cold pressor task, suggesting that cue-conditioned relaxation facilitates dissociation between sensory input and behavioral withdrawal.^[102] Similarly, operant conditioning approaches, pioneered by Fordyce in the 1970s, reinforce adaptive behaviors like sustained activity despite discomfort through positive contingencies, thereby increasing functional endurance and pain tolerance in chronic pain rehabilitation settings. This method has profoundly influenced multidisciplinary pain management by shifting focus from pain avoidance to rewarding persistence, with long-term applications demonstrating reduced disability and improved tolerance in patients with persistent pain conditions.^[103] Exercise regimens, particularly aerobic training, boost pain tolerance by elevating endorphin levels and activating endogenous opioid systems, leading to exercise-induced hypoalgesia (EIH). A comprehensive review indicates that moderate-intensity aerobic exercise, such as cycling or running at 70% VO2 max for 30 minutes, consistently increases pain thresholds and tolerance in healthy individuals, with effects persisting up to 30 minutes post-exercise, though responses vary in chronic pain populations.^[104] In a controlled training study, healthy participants undergoing 6 weeks of high-intensity interval cycling exhibited a 41% increase in pain tolerance on a tourniquet test, outperforming those in moderate continuous exercise, highlighting the role of intense aerobic protocols in enhancing endurance to ischemic pain.^[105] Other behavioral interventions, including hypnosis and yoga, yield sustained improvements in pain tolerance through structured protocols evaluated in randomized controlled trials (RCTs). Hypnosis protocols, often involving suggestive imagery and relaxation, have been found to elevate heat pain thresholds by approximately 0.74°C in healthy volunteers during a single VR-assisted session, with autonomic markers indicating reduced sympathetic arousal and enhanced analgesia.^[106] A meta-analysis of hypnosis RCTs confirms moderate reductions in pain intensity (effect size d = 0.60) and unpleasantness (d = 0.40), supporting its efficacy for tolerance-building over multiple sessions.^[107] Yoga interventions, typically involving 8-12 weeks of postures, breathing, and mindfulness, significantly extend cold pain tolerance; experienced practitioners endured painful stimuli more than twice as long as non-practitioners (85 seconds vs. 35 seconds), correlated with greater insular cortex gray matter volume that aids sensory reappraisal.^[108] RCTs of yoga programs report sustained gains in tolerance and reduced pain interference post-intervention, particularly in chronic low back pain cohorts.^[109] In endurance sports, training protocols explicitly target pain tolerance through progressive overload and psychological conditioning, as seen in runners and cyclists who develop superior modulation via repeated high-intensity sessions. Elite endurance athletes, such as long-distance runners, exhibit higher cold pain tolerance thresholds than non-athletes, attributed to habitual exposure in protocols like interval training that foster neural adaptations in descending pain inhibition pathways.^[2] These regimens, often incorporating psychological skills like goal-setting and imagery alongside physical drills, enable athletes to maintain performance under discomfort, with studies showing lower pain intensity ratings to thermal stimulation compared to non-athletes.^[110]

Pharmacological and Therapeutic Enhancements

Pharmacological agents play a key role in modulating pain tolerance by targeting specific receptors and pathways to inhibit nociceptive signaling. Opioids, such as morphine, bind to mu-opioid receptors in the central nervous system, elevating pain thresholds through suppression of pain transmission and enhancement of inhibitory neurotransmission.^[111] This mechanism provides potent short-term gains in tolerance, particularly for acute severe pain, but prolonged use often results in receptor desensitization, leading to analgesic tolerance and heightened risk of dependence.^[112]^[113] Non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and naproxen, contribute to improved pain tolerance by inhibiting cyclooxygenase (COX) enzymes, which reduces prostaglandin synthesis and subsequent peripheral inflammation that sensitizes nociceptors.^[114] This anti-inflammatory modulation is especially effective in conditions involving tissue damage, such as arthritis or sports injuries, where NSAIDs normalize elevated pain sensitivity without directly acting on opioid pathways.^[115] However, repeated administration can lead to tolerance to their antinociceptive effects, potentially mediated by endogenous opioid systems in descending pain modulatory circuits.^[116] Adjunct therapies further enhance tolerance through complementary mechanisms. Antidepressants like duloxetine, a serotonin-norepinephrine reuptake inhibitor, augment descending inhibitory pathways from the brainstem, restoring impaired pain modulation in chronic conditions such as fibromyalgia and diabetic neuropathy.^[117]^[118] Ketamine, functioning as an NMDA receptor antagonist, delivers acute tolerance boosts by preventing central wind-up and hyperalgesia, proving particularly beneficial in opioid-refractory or tolerant states during postoperative or neuropathic pain management.^[119]^[120] Clinical evidence underscores these benefits; a 2020 systematic review and meta-analysis of randomized trials demonstrated moderate-quality evidence that cannabinoids, such as nabiximols, reduce chronic non-cancer pain intensity by approximately 30%, indicating enhanced tolerance in long-term use.^[121] Despite these advantages, pharmacological enhancements carry limitations, including the development of tolerance to the agents themselves, which diminishes efficacy and may exacerbate pain sensitivity upon withdrawal.^[122] For opioids and ketamine, this involves adaptive changes in receptor signaling, while NSAIDs exhibit tolerance via indirect opioid involvement, necessitating careful dosing and monitoring to sustain therapeutic gains.^[123]

Applications and Implications

Clinical Pain Management Strategies

In clinical pain management, assessing individual pain tolerance profiles is integral to tailoring opioid prescribing practices, enabling clinicians to balance efficacy with risks such as dependency and overdose. The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain recommends evaluating patient-specific factors, such as the history and characteristics of pain, to inform dosing and duration, particularly for acute and chronic non-cancer pain scenarios.^[124] Similarly, the International Association for the Study of Pain (IASP) emphasizes a biopsychosocial evaluation in its interprofessional pain curriculum, incorporating sensory, emotional, and contextual elements of pain tolerance to guide comprehensive assessment and avoid over-reliance on pharmacological interventions alone.^[125] This approach helps mitigate adverse outcomes by considering patient-specific factors in opioid therapy.^[126] Multimodal therapy strategies integrate tolerance-building techniques with analgesics to optimize pain control while minimizing opioid use. These protocols combine non-opioid medications, such as acetaminophen and nonsteroidal anti-inflammatory drugs, with behavioral interventions like graded exposure to enhance endogenous pain modulation mechanisms.^[127] In postoperative settings, protocols adjust for patient-specific factors to customize analgesia regimens, reducing the incidence of severe pain and complications like prolonged recovery. For instance, enhanced recovery after surgery pathways employ this multimodal framework, achieving lower opioid consumption and improved functional outcomes by addressing individual variability in pain thresholds from the outset.^[127] Such strategies draw briefly on pharmacological enhancements, like gabapentinoids, to support tolerance modulation without escalating doses.^[128] For chronic conditions like fibromyalgia, cognitive behavioral therapy (CBT) targeted at pain tolerance offers a non-pharmacological avenue to improve symptom management. CBT interventions, including cognitive restructuring, have been shown to increase heat pain tolerance thresholds in fibromyalgia patients, fostering adaptive coping and reducing perceived pain intensity.^[129] This tolerance-focused CBT also diminishes pain catastrophizing, leading to sustained reductions in daily pain interference as evidenced in randomized trials.^[130] However, disparities in care persist, with ethnic biases in pain assessment contributing to undertreatment; studies indicate that clinicians often underrate pain in Black and Hispanic patients compared to white patients, exacerbating inequities in tolerance evaluation and therapeutic access.^[131] These biases, rooted in implicit stereotypes, result in lower analgesic prescriptions and poorer outcomes for minority groups across pain management contexts.^[132] Optimizing pain tolerance through these integrated strategies yields measurable outcomes, including reduced healthcare utilization. Personalized assessments and multimodal interventions correlate with fewer emergency visits and hospital readmissions, as patients with enhanced tolerance require less frequent interventions for pain exacerbations.^[133] In chronic pain cohorts, higher pain tolerance profiles are associated with lower overall service use, such as reduced primary care consultations, highlighting the economic and clinical benefits of tolerance-targeted care.^[134] This optimization not only improves quality of life but also alleviates system-wide burdens by promoting self-management and decreasing reliance on high-cost acute services.^[135]

Performance in Sports and Military Contexts

In sports, enhanced pain tolerance plays a crucial role in sustaining performance during prolonged or high-intensity efforts, particularly in endurance disciplines like marathon running. Mental toughness training programs, which incorporate psychological strategies such as goal-setting and visualization, help athletes push through discomfort, enabling marathoners to maintain pace despite accumulating fatigue and muscle pain.^[136] Studies on ultra-endurance athletes, such as participants in multi-stage ultramarathons, demonstrate significantly higher pain tolerance compared to non-athletes; for instance, ultra-marathon runners tolerated cold pain stimuli for 180 seconds on average, nearly double the 96 seconds endured by controls, reflecting adaptations from repeated exposure to physical stress.^[137] In military contexts, boot camp conditioning fosters injury resilience by progressively exposing recruits to physical stressors, building the capacity to function under pain and reducing dropout rates during rigorous training phases like Navy SEAL Hell Week, where participants endure over five days of continuous exertion with minimal sleep.^[138] Historical data from combat veterans indicate elevated pain thresholds and tolerance following severe injuries, with those experiencing major trauma showing substantially higher thermal pain endurance than lightly injured peers, likely due to conditioned responses to battlefield stress in special forces operations.^[139] Techniques such as biofeedback, which trains individuals to control physiological responses like heart rate variability, are integrated into athletic and military preparation to modulate pain perception and improve focus during demanding tasks.^[140] However, over-reliance on high pain tolerance poses risks, as athletes and soldiers may neglect early injury signals, leading to exacerbated damage; for example, in endurance sports, ignoring persistent discomfort can result in chronic overuse injuries due to diminished body awareness.^[141] Case studies from Olympic-level combat sports illustrate targeted pain management approaches. Elite judo and wrestling athletes often employ a combination of problem-focused strategies, such as activity modulation and pharmacological aids under medical supervision, alongside emotion-focused techniques like attention diversion, to compete through acute injuries while minimizing long-term harm, as evidenced in qualitative analyses of injured Olympic competitors.^[142] The International Olympic Committee's consensus on pain management emphasizes multidisciplinary interventions, including psychological support, to balance performance gains with health preservation in high-contact disciplines.^[143]

Research Gaps and Future Directions

Current research on pain tolerance reveals significant gaps, particularly in the representation of non-Western populations, where studies predominantly focus on Western cohorts, leading to disparities in understanding ethnic variations in pain processing and management.^[144] For instance, historical reviews indicate that ethnic minorities, including Indigenous and non-Hispanic groups, are underrepresented, resulting in biased generalizations about pain tolerance mechanisms across global populations.^[145] Additionally, longitudinal studies examining the plasticity of pain tolerance over time remain limited, with few investigations tracking changes in tolerance due to chronic exposure or interventions across extended periods, hindering insights into adaptive neural responses.^[146] Integration of AI-driven pain prediction models into tolerance research faces challenges, such as data biases and the lack of domain-specific datasets, which complicate accurate forecasting of individual tolerance levels in clinical settings.^[147] Outdated research paradigms from the pre-2010s era often emphasized binary sex differences in pain tolerance without accounting for intersectionality, overlooking how factors like socioeconomic status, race, and gender identity interact to influence pain experiences.^[148] This narrow focus has contributed to persistent inequities in pain care, as evidenced by reviews highlighting the need for more inclusive frameworks that integrate these intersecting variables.^[149] Furthermore, the influence of the gut microbiome on neural pain pathways has been largely neglected until emerging 2020s research, which demonstrates how microbial dysbiosis modulates central sensitization and tolerance via the gut-brain axis, yet comprehensive studies remain sparse.^[150] Future directions in pain tolerance research should leverage advancements in neuroimaging, such as real-time functional MRI (fMRI), to enable dynamic monitoring and training of tolerance responses during pain provocation tasks, potentially revolutionizing behavioral interventions.^[151] Personalized medicine approaches, informed by genomics, offer promise for tailoring tolerance-enhancing therapies based on genetic variants affecting pain sensitivity and opioid responsiveness, with next-generation sequencing poised to identify biomarkers for individualized strategies.^[152] Ethical considerations in AI for tolerance assessment are paramount, addressing issues like algorithmic bias, data privacy, and explainability to ensure equitable and transparent applications in diverse populations.^[153] To advance the field, there is a pressing need for standardized global protocols, as part of the International Association for the Study of Pain (IASP)'s Global Year 2025 initiatives, which prioritize research in low- and middle-income settings and emphasize inclusive methodologies for pain tolerance studies.^[154] These protocols aim to foster cross-cultural validation of measurement tools and promote collaborative efforts to bridge existing gaps, ultimately improving translational outcomes in pain management.^[155]

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Comprehensive pain assessment and management is multidimensional (i.e., sensory, emotional, cognitive, developmental, behavioral, spiritual, cultural) and ...
[124]
[PDF] Opioid Therapy for Chronic Pain - VA.gov
Tolerance is a form of neuroadaptation to the effects of chronically administered opioids (or other medications), which is manifested by the need for increasing ...
[125]
Multimodal analgesia as an essential part of enhanced recovery ...
Enhanced recovery after surgery protocols are multimodal perioperative care pathways designed to achieve early recovery in patients after surgical procedures.
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Multimodal Approaches to Pain Management: Analgesics, Adjuvants ...
Jun 3, 2025 · These treatments help reduce medication reliance, improve functional outcomes, and enhance patients' quality of life. In addition, integrating ...
[127]
Do fibromyalgia patients benefit from cognitive restructuring and ...
Cognitive restructuring strategies were effective in increasing heat pain tolerance. · Acceptance strategies were effective in increasing heat pain tolerance.
[128]
A Randomized Controlled Neuroimaging Trial of Cognitive ...
Sep 20, 2023 · This randomized controlled mechanistic trial was designed to assess CBT's effects on pain catastrophizing and its underlying brain circuitry.
[129]
Racial bias in pain assessment and treatment recommendations ...
Apr 4, 2016 · The present work examines beliefs associated with racial bias in pain management, a critical health care domain with well-documented racial ...
[130]
Racial Bias in the Treatment and Management of Pain - JAMA Network
Jun 9, 2022 · Several studies have reported associations between Black patients' experiences of perceived bias and discrimination with worse pain outcomes.
[131]
Comprehensive Review on Personalized Pain Assessment and ...
Jun 5, 2025 · Emerging evidence indicates that combining personalized pain assessment with multimodal interventions can significantly improve clinical outcomes.
[132]
The effect of pain tolerance on healthcare utilization among patients ...
Results from this study demonstrated that patients with a lower perception of pain tolerance were more likely to have higher healthcare utilization than those ...
[133]
Prediction of healthcare utilization following an episode of physical ...
Aug 20, 2018 · Baseline disability and 4-week change in pain intensity were important global predictors of subsequent healthcare utilization. Age, insurance ...
[134]
Does mental toughness predict physical endurance? A replication ...
The purpose of this study was to replicate Crust and Clough's (2005) investigation of the relationship between mental toughness and physical endurance.
[135]
Ultra-Marathon Runners Are Different: Investigations into Pain ...
Aug 7, 2025 · Interestingly, ultra-endurance athletes seem to be very good at dealing with pain: A study with ultraendurance runners who competed in a 4487km ...
[136]
Hell Week | Navy SEALs
Hell Week is a 5 1/2 day, brutally difficult training with little sleep, testing physical and mental endurance, and only 25% of candidates make it through.
[137]
The effect of past-injury on pain threshold and tolerance - Lippincott
Veterans who had been severely injured had much higher threshold and tolerance for thermal pain as compared to lightly injured veterans.
[138]
Effects of a Heart Rate Variability Biofeedback Intervention on ...
Dec 15, 2017 · The purpose of the study was to examine whether HRV biofeedback would improve athletes' pain catastrophizing and psychological responses ...Missing: tolerance | Show results with:tolerance
[139]
[PDF] Pain tolerance in sport - Baltic Journal of Health and Physical Activity
The saying. “no pain, no gain” perfectly describes the risk of an injury in sport as well as the expectations of high tolerance of pain. Sociologists note ...
[140]
Injury‐Related Acute Pain in Elite Sport: A Model of Athletes' Pain ...
This study aims to elicit the “how” and “why” of acute pain management strategies when coping with sport injuries. A thematic analysis of qualitative data ...
[141]
[PDF] International Olympic Committee consensus statement on pain ...
This consensus paper fulfils the IOC charge by addressing the multifaceted aspects of pain physi- ology and pain management in elite athletes through the lenses ...Missing: combat | Show results with:combat
[142]
A historical review of pain disparities research - PubMed Central - NIH
This theory-guided review draws on 30 years of published data to examine and interrogate the current and future state of pain disparities research.
[143]
An integrative review of the lived experiences of chronic pain among ...
Our findings highlight the layered and complex aspects of the lived experiences of chronic pain among Indigenous people.Missing: tolerance | Show results with:tolerance
[144]
[PDF] Longitudinal studies - UQ eSpace - The University of Queensland
May 17, 2021 · Using PCs can address gaps in current knowledge by improving our understanding of pain sensitivity, and other factors, in relation to the ...
[145]
artificial intelligence in pain medicine, opportunities and challenges
May 11, 2023 · One of the pain medicine specific challenges associated with AI integration is that, unlike clinical domains such as cancer or cardiovascular ...
[146]
Chronic Pain: Analyzing Sex, Gender, and Intersectionality
Researchers have demonstrated that these gender norms can be changed and that this can impact perceived sensitivity to pain (Robinson et al., 2003). Thus, ...Missing: outdated | Show results with:outdated
[147]
Sex-Related Differences in Chronic Pain: A Narrative Review by a ...
Jun 28, 2025 · However, chronic pain research has insufficiently addressed sex and gender differences, contributing to suboptimal and inequitable care. This ...Missing: intersectionality | Show results with:intersectionality
[148]
The brain-gut axis and chronic pain: mechanisms and therapeutic ...
Feb 14, 2025 · Microbial neurotransmitters, including GABA and serotonin, interact with the CNS via the vagus nerve, influencing mood and pain perception.Missing: 2020s | Show results with:2020s
[149]
Real-time fMRI applied to pain management - PMC - PubMed Central
Traditional fMRI experiments involve engaging in or changing a specific behavioral or cognitive task in order to measure the effect on neural function.Missing: advancements tolerance
[150]
Next-generation precision medicine for pain | Molecular Psychiatry
Aug 25, 2025 · Our goal is to identify biomarkers that track pain regardless of whether the cause is due to internal biology or prompted by exogenous ...Missing: tolerance | Show results with:tolerance
[151]
4 Ethical Challenges of AI in Pain Assessment (With Solutions)
Jan 7, 2025 · AI's Role in Pain Assessment · Bias and Fairness · Transparency and Explainability · Patient Autonomy and Consent · Human Oversight · Bridging ...
[152]
Setting Clinical Pain Research Priorities in Low- and Middle-Income ...
Apr 2, 2025 · The 2025 Global Year will examine pain management and education beyond low- and middle-income countries to include low-income settings and ...
[153]
“Translating Pain Knowledge into Clinical Practice”: Published ...
Jun 23, 2025 · The program also helped establish standardized neonatal pain assessment and management protocols, now being used throughout the neonatology ...