Pain tolerance varies enormously from person to person, and if yours feels unusually low, there is almost certainly a real, biological explanation behind it. Research estimates that roughly 40 percent of the variation in pain sensitivity is heritable, with specific genetic profiles causing two- to threefold differences in how intensely people experience the same stimulus.1Philosophical Transactions of the Royal Society B: Biological Sciences. An evolutionary medicine perspective on pain and its disorders That genetic contribution, though, is only the beginning. Sleep quality, hormone levels, inflammation, psychological state, childhood experiences, and even the bacteria in your gut all dial pain sensitivity up or down in ways that are measurable and, in many cases, modifiable.
Your Genes Set the Baseline
One of the best-studied genetic players in pain sensitivity is an enzyme called COMT, which breaks down stress-related chemicals like adrenaline and dopamine. Variants of the COMT gene that slow the enzyme down lead to higher circulating levels of those chemicals, and the result is a measurably lower pain tolerance. Animal studies have confirmed that pharmacologically inhibiting COMT increases sensitivity to both pressure and heat.2PubMed Central. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors In humans, one well-known variant of this gene (the Met allele at position 158) has been linked not only to heightened experimental pain sensitivity but also to a greater risk of developing lasting pain after events like lumbar disc herniation.3PubMed. The COMT rs4680 Met allele contributes to long-lasting low back pain, sciatica and disability after lumbar disc herniation
Your body’s built-in painkilling system matters just as much. Endogenous opioids, the natural counterparts to drugs like morphine, are constantly modulating how much pain gets through to conscious awareness. People differ in both the baseline level of these natural opioids and the density of the receptors they bind to in the brain. Those differences significantly influence how pain is perceived and tolerated across different populations.4PubMed Central. Opioidergic tone and pain susceptibility: interactions between reward systems and opioid receptors If your opioid tone runs low, or your receptors are sparse, you are working with a weaker internal brake on pain signals, and you will feel things more intensely than someone whose system runs higher.
The Red Hair Connection
One of the more striking examples of genetic influence on pain comes from research on people with naturally red hair. The MC1R gene, which is responsible for red hair pigmentation, also appears to alter pain processing in surprising ways. A study in mice found that loss of MC1R function in melanocytes (skin pigment cells) lowers levels of a hormone called alpha-MSH in the bloodstream, which in turn lifts suppression on the brain’s opioid system and actually raises baseline pain thresholds.5PubMed Central. Reduced MC4R signaling alters nociceptive thresholds associated with red hair A large genetic study using data from the UK Biobank found that certain MC1R variants were associated with a reduced count of persistent pain conditions, suggesting a protective effect.6PubMed Central. Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor
The picture is not entirely straightforward, though. A narrative review examining all available evidence found that red-haired women may actually have increased sensitivity to certain types of pain, while homozygous carriers of MC1R variants sometimes show higher tolerance. Responses to anesthetics and painkillers also seem altered, with some studies reporting that redheads need more anesthetic and others finding they respond better to opioid-based pain relief.7PubMed Central. Red-Haired People’s Altered Responsiveness to Pain, Analgesics, and Hypnotics: Myth or Fact?-A Narrative Review The takeaway is that even a single gene can push pain sensitivity in different directions depending on the context, which helps explain why people with similar backgrounds can have wildly different experiences of the same stimulus.
How Poor Sleep Quietly Amplifies Pain
If you are sleeping badly, your pain tolerance is almost certainly taking a hit. A systematic review and meta-analysis found that even fragmented sleep, not just total deprivation, significantly reduces both pain threshold and pain tolerance in healthy people.8Sleep Medicine Reviews. The differential effects of sleep deprivation on pain perception in individuals with or without chronic pain: A systematic review and meta-analysis Lab experiments in young healthy adults confirmed that a single night of disrupted sleep measurably increased pain sensitivity the next day.9PubMed Central. Effects of Sleep Fragmentation and Induced Mood on Pain Tolerance and Pain Sensitivity in Young Healthy Adults
The mechanism goes deeper than just feeling groggy. One study that kept participants awake for an entire night found that total sleep deprivation impaired the brain’s descending pain-inhibition pathways, made the spinal cord more excitable, and sensitized peripheral nerves to cold and pressure.10PubMed Central. Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants In other words, bad sleep does not just make you grumpier about pain; it physically rewires the system that filters pain signals before they reach your conscious brain. If you are wondering why your pain tolerance seems worse than it used to be, evaluating your sleep habits is a reasonable first step.
Hormones and Why Pain Can Differ by Sex
Testosterone has a measurable antinociceptive effect, meaning it raises the threshold at which stimuli register as painful. A study comparing men with low testosterone to men with normal levels found that the low-testosterone group had significantly lower pain thresholds and pain tolerance, and that free testosterone levels were positively correlated with tolerance.11PubMed Central. Exploring the Influence of Testosterone on Pain Perception and Modulation Among Men with Low and Normal Testosterone Concentrations This is one factor that contributes to the well-documented sex difference in pain: on average, biological males have higher pain thresholds than biological females in experimental settings.
Estrogen’s role is more complicated. Rather than simply raising or lowering pain sensitivity, fluctuations in estrogen appear to increase pain intensity and perception, which helps explain why many women experience heightened pain at certain points in the menstrual cycle.12PubMed Central. The Role of Sex Hormones in Pain-Related Conditions If you have noticed that your pain tolerance seems to wax and wane on a monthly schedule, hormonal cycling is a likely explanation. Conditions that disrupt hormone levels, whether thyroid disorders, menopause, or low testosterone in men, can shift pain sensitivity in ways that feel sudden and confusing if you are not aware of the connection.
When Your Nervous System Gets Stuck on High Alert
Pain is not just a signal sent from an injury site to the brain. Your central nervous system actively decides how much of that signal to amplify and how much to suppress. In a healthy state, there is a balance between circuits that ramp pain up (facilitatory) and circuits that dampen it (inhibitory). When that balance tilts toward facilitation, pain perception intensifies and can become self-sustaining. Growing evidence supports the concept that disruption of this balance, favoring facilitation, may promote and maintain chronic pain states.13PubMed Central. Descending pain modulation and chronification of pain
This process, broadly called central sensitization, is especially relevant if you already live with a chronic pain condition. In fibromyalgia, for example, neuroinflammation and overactive immune cells in the spinal cord amplify pain signals well beyond what the original stimulus would warrant.14PubMed Central. Melatonin Mitigates Central Sensitization and Nociplastic Pain in Spinal Cord and Dorsal Root Ganglia of FM Rat Model Even certain medications can trigger this kind of sensitization. Chemotherapy drugs like cisplatin have been shown to activate immune-signaling pathways in spinal cord cells that heighten pain sensitivity long after treatment ends.15PubMed. Microglial P2Y12 Signaling Contributes to Cisplatin-induced Pain Hypersensitivity via IL-18-mediated Central Sensitization in the Spinal Cord The unsettling reality is that pain itself can make future pain worse by remodeling how the nervous system processes incoming signals.
Inflammation You May Not Notice
You do not need to have a visible injury or an obvious illness for inflammation to lower your pain tolerance. When researchers deliberately triggered a mild systemic inflammatory response in healthy volunteers using a bacterial component called endotoxin, pressure pain thresholds dropped by about 20 percent and electrical pain thresholds fell by about 13 percent. More participants were also unable to complete a standard cold-water pain test compared to controls.16PubMed Central. Systemic Inflammation Decreases Pain Threshold in Humans In Vivo That is a meaningful shift from a level of inflammation so mild that participants were not visibly sick.
Specific inflammatory molecules play a direct role. Cytokines like IL-6 and IL-17 sensitize pain-sensing nerve fibers by altering the ion channels those nerves use to fire, effectively lowering the activation threshold so that stimuli that would not normally hurt start registering as painful.17Exploration of Immunology. Evolving role of immunology in chronic pain medicine: tissue necrosis factor and interleukin modulatory treatments Chronic low-grade inflammation, the kind associated with obesity, autoimmune conditions, poor diet, and sedentary behavior, could be silently turning up your pain volume without producing any obvious symptoms that say “you’re inflamed.”
Your Mind Is Not Separate From the Signal
Psychological state is not a polite footnote in pain science; it is one of the strongest modulators. Research on the mechanisms of pain tolerance found that pain catastrophizing, the tendency to ruminate on and magnify the threat of pain, directly increased negative expectancies about an upcoming painful stimulus, and those expectancies in turn predicted both how intense the pain felt and how long participants could endure it.18PubMed Central. The mechanisms of pain tolerance and pain-related anxiety in acute pain Anxiety operated through the same pathway. This is not a matter of “it’s all in your head.” The expectancy and emotional state alter the actual neural processing of the pain signal before it reaches conscious awareness.
Stress history matters too. Chronic stress disrupts the hypothalamic-pituitary-adrenal (HPA) axis, the body’s central stress-response system. In people with subacute back pain, researchers found abnormal cortisol suppression patterns and altered stress feedback sensitivity compared to both healthy controls and people with established chronic pain. In that group, cortisol levels were negatively associated with pain intensity, and the relationship was mediated by cold pain thresholds and anxiety.19Elsevier. Hypothalamic-pituitary-adrenal axis feedback sensitivity in different states of back pain A stress system that is stuck in overdrive, or paradoxically burned out, changes the neurochemical environment in which every pain signal gets processed.
Childhood Experiences Leave a Lasting Mark
The relationship between early adversity and adult pain sensitivity is real, but the direction of the effect is more nuanced than you might expect. In one study of adults, the severity of childhood emotional abuse was significantly associated with decreased heat pain tolerance, even after controlling for other forms of adversity. Physical abuse, sexual abuse, and neglect did not show the same association, suggesting something specific about emotional abuse and the affective component of pain processing.20PubMed Central. Childhood adversities and laboratory pain perception
A study in high-risk adolescents found a somewhat counterintuitive pattern: across multiple maltreatment types, more severe maltreatment was actually associated with lower pain sensitivity in lab tests, meaning these individuals tolerated higher temperatures and colder temperatures before reporting pain. The largest effect was for physical neglect, where individuals above the severe neglect cutoff tolerated temperatures roughly three degrees more extreme than non-neglected peers.21The Journal of Pain. The association between childhood maltreatment and pain sensitivity in a high-risk adolescent population One interpretation is that chronic adversity can produce a kind of sensory blunting or dissociation in controlled lab settings, while simultaneously priming the person for greater clinical pain and suffering in real-world contexts. The lab measure and the lived experience can point in different directions.
Epigenetic Changes and the Pain Volume Knob
Beyond the DNA sequence you inherited, the way your genes are read can shift over your lifetime. Painful experiences themselves appear to alter chemical marks on DNA and on the histone proteins that package it, and these epigenetic changes may help maintain heightened pain sensitivity long after the initial cause resolves.22PubMed Central. Epigenetic regulation of chronic pain This is one reason chronic pain conditions sometimes worsen over time even in the absence of ongoing tissue damage. The nervous system’s gene-expression profile has been physically altered to favor pain amplification.
Your Gut May Be Involved
Research on the gut-brain axis has increasingly implicated the trillions of microbes living in your intestines as players in pain modulation. Gut microbial communities influence pain perception by regulating both central and peripheral sensitization mechanisms across multiple types of pain.23PubMed Central. Gut microbiota-mediated pain sensitization: mechanisms and therapeutic implications One of the key mediators appears to be short-chain fatty acids, metabolites produced when gut bacteria ferment dietary fiber. Butyrate, a major short-chain fatty acid, has been shown to reduce pain behaviors in animal models of nerve injury and to relieve abdominal pain in patients with inflammatory bowel conditions. Butyrate levels were found to be dramatically reduced in stool samples from patients with these conditions.24British Journal of Anaesthesia. Pain regulation by gut microbiota: molecular mechanisms and therapeutic potential A fiber-poor diet that starves these bacteria could plausibly contribute to a lower pain tolerance, though human clinical trials targeting the microbiome for pain management are still in early stages.
What You Can Actually Do About It
Exercise is one of the most accessible tools for raising pain tolerance. A meta-analysis of 36 studies found a statistically significant increase in pain threshold after exercise, with the effect being somewhat larger in women and after strength-based exercise at moderate intensity.25PubMed Central. Exercise-induced pain threshold modulation in healthy subjects: a systematic review and meta-analysis A separate trial confirmed that even low- and moderate-intensity aerobic exercise increased pressure pain thresholds across multiple body sites.26PubMed Central. Effects of Exercise-Induced Hypoalgesia at Different Aerobic Exercise Intensities in Healthy Young Adults The underlying mechanisms are thought to involve the brain’s opioid and endocannabinoid systems, along with serotonin pathways, and the combination of exercise intensity and duration matters more than either variable alone.27PubMed Central. Understanding Exercise-Induced Hypoalgesia: An Umbrella Review of Scientific Evidence and Qualitative Content Analysis
Mindfulness meditation offers a different route to the same destination. Brain imaging studies have shown that meditation reduces pain intensity and unpleasantness by activating brain regions involved in cognitive regulation of pain, while simultaneously quieting regions that relay raw sensory information to higher-order areas.28PubMed Central. Brain mechanisms supporting the modulation of pain by mindfulness meditation A more recent study confirmed that mindfulness meditation produced greater reductions in both pain intensity and pain unpleasantness than placebo cream, sham meditation, and control conditions, engaging distinct neural signatures from placebo.29PubMed Central. Mindfulness Meditation and Placebo Modulate Distinct Multivariate Neural Signatures to Reduce Pain It is not just a distraction technique; it appears to genuinely change how the brain constructs the pain experience from incoming nerve signals.
Vitamin D is worth mentioning, though the evidence is mixed. A review of supplementation studies found that five trials with 400 total participants showed a positive correlation between vitamin D supplementation and improved pain ratings, while four other trials with 220 participants found no change.30PubMed Central. Vitamin D Deficiency and Pain: Clinical Evidence of Low Levels of Vitamin D and Supplementation in Chronic Pain States If you are deficient, correcting it is unlikely to hurt and may help, but it is not a reliable standalone strategy for someone with genuinely low pain tolerance.
How Aging Changes Pain Perception
If you feel like pain has changed as you have gotten older, the science confirms that something real is happening, though not in the direction most people assume. Heat pain thresholds increase with age: in one study, older adults required temperatures averaging about 46°C to report pain, compared to about 43°C for younger adults.31Age and Ageing. Age-associated changes in multimodal pain perception That might sound like a benefit, but it is actually a sign of nerve degeneration. The pain-sensing fibers are less responsive, which means older adults may fail to detect harmful stimuli that a younger nervous system would flag immediately. Meanwhile, pressure pain thresholds do not change much with age, and the central processing of chronic pain can become more burdensome as descending inhibitory systems weaken. The net result is a paradox: older adults may seem tougher in laboratory pain tests while simultaneously experiencing more suffering from clinical pain conditions.
This is worth keeping in mind if you are comparing your pain tolerance to an older relative who seems unbothered by things that bother you. Their nervous system may simply be less sensitive to certain stimuli, not “tougher” in a way that reflects better pain modulation.