The body's own pain relief system: how exercise influences pain sensitivity

There's something particularly satisfying about finishing a good run.

You might feel happier, more relaxed or mentally refreshed. There's often a sense of accomplishment, and those positive feelings can linger after you've stopped exercising.

The reasons for this are complex. Exercise influences several physiological processes involved in mood and stress regulation, while psychological factors such as enjoyment and accomplishment also contribute.

But there's another fascinating effect of physical activity that receives less attention: exercise can temporarily reduce our sensitivity to pain.

Our bodies produce chemical substances involved in regulating pain, including endogenous opioids and endocannabinoids. Exercise can influence these systems, offering an interesting insight into how physical activity affects the nervous system.

Understanding these processes gives us another reason to appreciate physical activity, including walking, cycling, swimming and other recreational activities outside structured gym sessions.

Our bodies produce their own opioids

Most people associate opioids with medications used to manage pain.

The human body also produces its own opioid substances, known as endogenous opioids.

These include beta-endorphins, enkephalins and dynorphins, which interact with opioid receptors in the nervous system.

They participate in several physiological processes, including pain modulation, stress responses and aspects of emotional regulation. [1]

Pain is influenced by complex interactions involving the brain, spinal cord and peripheral nervous system.

Endogenous opioids are part of these processes. Their activity can influence how pain-related information is transmitted and processed.

Exercise can stimulate activity within the body's opioid system.

Research has demonstrated increases in circulating endogenous opioids following physical exertion, although the response varies with factors such as exercise intensity and duration. [1]

There is also evidence that exercise can influence opioid activity within the brain itself.

In a study published in Cerebral Cortex, Boecker and colleagues used positron emission tomography (PET) to investigate opioid activity before and after prolonged running in ten trained male athletes.

Following exercise, researchers observed changes in opioid receptor binding across brain regions involved in emotional processing. These changes were also associated with participants' reported feelings of euphoria. [2]

Although the study was small, it provided evidence of central opioid activity associated with prolonged exercise.

One important distinction is that measuring endorphins in the bloodstream doesn't necessarily tell us what is happening inside the brain.

Circulating beta-endorphins and opioid activity within the central nervous system need to be considered separately. Researchers use methods such as brain imaging to investigate these central responses.

The findings provide an interesting foundation for understanding the relationship between exercise and pain regulation.

What happens to pain sensitivity after exercise?

Researchers have identified a phenomenon known as exercise-induced hypoalgesia.

Hypoalgesia refers to a reduction in pain sensitivity.

During research studies, participants may have their sensitivity to a controlled painful stimulus measured before and after exercise.

Under some conditions, participants become less sensitive to that stimulus following physical activity.

A systematic review and meta-analysis by Wewege and Jones examined this response in healthy individuals and people experiencing chronic musculoskeletal pain.

The review found evidence that aerobic exercise can reduce experimentally measured pain sensitivity in healthy participants. Dynamic resistance exercise also demonstrated a smaller effect, although the available studies involved relatively few participants. [3]

The findings suggest that physical activity can temporarily influence the way the nervous system responds to painful stimuli.

Endogenous opioids are one possible contributor.

These substances interact with pain-modulating pathways that can influence the transmission and processing of pain-related information.

However, the mechanisms behind exercise-induced hypoalgesia remain complex. Other systems, including endocannabinoids, may also contribute.

There is also an important distinction between experimental pain sensitivity and someone's experience of persistent musculoskeletal pain.

The same review found that evidence for exercise-induced hypoalgesia in people with chronic musculoskeletal pain was limited and uncertain. [3]

Some individuals experience reduced symptoms during or after activity. Others may notice little immediate change or experience increased discomfort.

The presence of exercise-induced hypoalgesia in research helps us understand pain physiology, but it doesn't establish that a particular exercise session will relieve someone's existing pain.

Endocannabinoids: another pain-regulating system

The endogenous opioid system is one part of the body's pain-modulating physiology.

Another group of naturally occurring signalling substances, called endocannabinoids, has attracted considerable research interest.

Endocannabinoids interact with cannabinoid receptors and participate in processes involving pain regulation, stress responses, mood and several other physiological functions.

Two important endocannabinoids are anandamide, also known as AEA, and 2-arachidonoylglycerol, or 2-AG.

Researchers have investigated how exercise influences circulating levels of these substances.

A review by Siebers and colleagues found that most of the included studies examining acute exercise reported increases in circulating endocannabinoids, although the responses varied across exercise protocols. [4]

This is particularly interesting because the endocannabinoid system has been implicated in both pain modulation and the pleasurable experiences sometimes associated with sustained exercise.

It has also prompted researchers to reconsider a familiar explanation of the runner's high.

Understanding the runner's high

The runner's high is a temporary experience of euphoria or unusual wellbeing that some people report during sustained running or other endurance exercise. It may continue after the activity ends.

For many years, this experience was commonly attributed to endorphins.

The relationship is now understood to be more complex.

Endocannabinoids have emerged as important candidates in explaining aspects of the runner's high.

In a human experiment published in Psychoneuroendocrinology, Siebers and colleagues investigated whether the positive emotional effects of running depended on endogenous opioid activity.

The researchers used naltrexone, a medication that blocks opioid receptors, to examine what happened when opioid signalling was inhibited.

Participants still experienced exercise-related improvements in mood and reductions in anxiety despite opioid receptor blockade. [5]

This suggests that endogenous opioid signalling is not essential for these particular effects.

The study also identified exercise-related changes in circulating endocannabinoids.

A subsequent review found that endocannabinoids remain promising candidates for explaining the runner's high, although their precise causal role in humans has not been established. [4]

These findings highlight how difficult it can be to attribute a familiar human experience to one specific chemical system.

The runner's high also needs to be distinguished from the more general sense of wellbeing someone might experience after exercise.

Feeling happier, calmer or accomplished after a run doesn't necessarily mean someone has experienced a runner's high.

Those feelings may reflect a combination of physiological and psychological influences, with considerable variation between individuals.

Does exercise intensity matter?

The type and intensity of exercise appear to influence some of these physiological responses.

Studies examining endogenous opioids and endocannabinoids have often used sustained aerobic activities such as running and cycling.

Research on endocannabinoids has identified differences in the response across exercise intensities, with moderate-intensity activity producing larger changes than lower-intensity activity in some experimental conditions. [1,4]

Similarly, research on exercise-induced hypoalgesia has investigated aerobic and resistance exercise performed under different protocols.

These findings make exercise intensity an interesting consideration when studying pain modulation.

However, there is no established intensity or duration that reliably produces a particular neurochemical response or reduction in pain for everyone.

Individual fitness and physical capacity also influence how demanding an activity feels.

A brisk walk or hilly hike may be physically challenging for one person and relatively comfortable for another.

Cycling, swimming, stair climbing and recreational activities can also involve quite different levels of effort depending on how they're performed.

And activities that don't produce a noticeable change in mood or pain sensitivity can still provide meaningful health benefits.

This is worth remembering when considering how exercise fits into everyday life.

Physical activity outside the gym

From an exercise physiology and rehabilitation perspective, I find this research particularly interesting.

When someone experiences persistent musculoskeletal pain, much of the attention can centre on clinical treatment and prescribed rehabilitation exercises.

Those interventions may play an important role in rebuilding strength, movement confidence and physical capacity.

But someone's physical activity extends well beyond their appointments or structured exercise sessions.

Walking, cycling, swimming, hiking and other recreational activities provide opportunities to move, develop physical fitness and participate in activities they enjoy.

Depending on the type, intensity and individual response, these activities may also influence pain sensitivity and some of the neurochemical systems we've discussed.

Consider someone recovering from an episode of back pain.

They may be gradually returning to resistance training or working through a structured rehabilitation program.

An enjoyable walk, swim or bike ride could provide another opportunity for movement, physical conditioning and confidence.

The activity might also help them feel more relaxed or comfortable.

There may be several reasons for that response, including physiological changes, enjoyment, stress regulation and the circumstances in which the activity takes place.

We cannot determine which mechanism is responsible for an individual's experience simply because they report feeling better afterwards.

But the broader point remains valuable: physical activity can contribute to health and wellbeing in ways that extend beyond the specific exercise adaptations we're targeting in the gym.

Putting it into practice

The idea that our bodies produce substances involved in regulating pain is fascinating.

Endogenous opioids and endocannabinoids form part of the nervous system's own chemical signalling processes, and exercise can influence their activity.

Research into these systems is helping us understand how physical activity affects pain sensitivity, stress and aspects of emotional wellbeing.

There are still important questions about how these responses differ between individuals, which exercise conditions influence them most strongly and how they relate to longer-term pain management.

Exercise-induced changes in endogenous opioids should also be distinguished from the effects of prescribed opioid medications. The research does not establish exercise as an equivalent replacement for medical pain relief.

For everyday life, the practical implications are encouraging.

Physical activity provides opportunities to develop fitness, strength and physical capacity. Individual exercise sessions may also influence pain sensitivity, stress and how we feel.

That activity can take many forms.

Running, swimming, cycling, hiking and walking outdoors can all contribute to an active lifestyle.

For people managing persistent pain, suitable leisure-time physical activity may be a valuable part of maintaining wellbeing and rebuilding physical capacity alongside appropriate rehabilitation.

Our bodies have remarkable systems for regulating pain and responding to physical activity. Understanding them gives us another perspective on why movement matters.

For further reading about pain sensitivity, beliefs and returning to meaningful activity, explore TF Allied Health's article:

Understanding pain: protection, sensitivity and rebuilding confidence →

References

1. Basso JC, Suzuki WA. The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review. Brain Plasticity. 2017;2(2):127–152. Source ↗

2. Boecker H, Sprenger T, Spilker ME, et al. The Runner's High: Opioidergic Mechanisms in the Human Brain. Cerebral Cortex. 2008;18(11):2523–2531. Source ↗

3. Wewege MA, Jones MD. Exercise-Induced Hypoalgesia in Healthy Individuals and People With Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis. The Journal of Pain. 2021;22(1):21–31. Source ↗

4. Siebers M, Biedermann SV, Fuss J. Do Endocannabinoids Cause the Runner's High? Evidence and Open Questions. The Neuroscientist. 2023;29(3):352–369. Source ↗

5. Siebers M, Biedermann SV, Bindila L, Lutz B, Fuss J. Exercise-induced euphoria and anxiolysis do not depend on endogenous opioids in humans. Psychoneuroendocrinology. 2021;126:105173. Source ↗