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Theories and mechanisms of the experience of pain

This is an excerpt from Psychological Benefits of Exercise and Physical Activity, The by Jennifer L. Etnier.

The experience of pain is a hard-wired phenomenon that is expected to help us avoid situations that might cause tissue damage. As previously described, if you accidentally touch something hot like a handle on a pot, the pain you experience is a critical signal telling you to move away from the heat source to minimize tissue damage. In this example, the heat provides a noxious stimulus that signals the brain to respond. Noxious stimuli can be thermal (hot or cold), chemical (internal or external), or mechanical (force or pressure).

I triple-dog dare you. Thinking of the noxious stimulus of cold reminds me of the scene in A Christmas Story where Flick, Ralphie’s friend, was triple-dog dared to touch his tongue to the school flagpole when the temperature outside was well below freezing. Although this scene was shot using movie magic so that the actor playing Flick wasn’t actually hurt, we can all probably imagine the sensation of your tongue being frozen to something metal. The painful experience portrayed by Flick was very believable and relatable.

When we consider the physiology of pain, a series of events happens in response to a noxious stimulus (figure 8.1). When tissue is damaged, algogenic substances are released in the tissue at the point of the stimulus. These substances promote immune system activity, cause inflammation, and activate the nerve endings of the nociceptors to signal pain. Nociceptors are specialized free nerve endings or neurons that are present in nearly all of our tissues and serve the explicit and unique function of transmitting a pain signal. When nociceptors are exposed to a noxious stimulus, they generate electrical signals that transmit information to the spinal cord via the afferent nerves (peripheral nerves that deliver a signal to the central nervous system) to be delivered to the brain for interpretation. The speed at which the information is transmitted along the afferent nerves is dependent on the specific fiber type that is transmitting the information. The myelinated A-delta fibers are used for the rapid transmission of a pain message for sharp, localized, and distinct pains. These fibers pass through the thalamus on the way to the motor and sensory areas of the cortex. This allows for a quick response. By contrast, the unmyelinated C fibers provide a slow transmission of pain messages in response to noxious stimuli that are more diffuse and that would be described as dull or aching. Once transmitted to the dorsal horn of the spinal cord, substance P (a neuropeptide) and glutamate (a neurotransmitter) are released in the dorsal horn, which facilitates the transmission of the pain signal up the ascending tracts of the spinal cord to areas of the brain including the brainstem, thalamus, cerebral cortex, and limbic system. It is in these regions that the pain signal is interpreted, resulting in behavioral, emotional, and cognitive responses.

Figure 8.1 When a pain-inducing stimulus is applied, the signal is transmitted to the brain by nociceptors (A-delta fibers and C-fibers) through the spinal cord to the brain.

The gate-control theory of pain (Melzack and Wall, 1965) proposes that the spinal cord has a gating mechanism that can be opened or closed to influence the amount of signal transmitted to the brain. The gate is thought to be housed in the spinal cord dorsal horn and to exert its effects on the small-diameter A-delta and C fibers that deliver the signal of pain up the spinal cord to the brain. The aperture of the gate is thought to be controlled by inhibitory neurons in the spinal cord that might attenuate the pain signals being delivered by narrowing the gate. According to this theory, when more activity or a stronger signal is transmitted via the pain fibers, this causes the gate to open. This makes sense because a more intense noxious stimulus (e.g., a hotter iron, a harder blow, a louder noise) needs to be responded to as quickly as possible. The gate is also thought to be controlled by a person’s emotions, with positive emotions (e.g., joy or happiness) closing the gate and negative emotions (e.g., anxiety or sadness) opening the gate. This theoretical hypothesis is supported by the anecdote about Kerri Strug, which illustrates how a person who is focused completely on their competitive performance might not feel the pain of an injured ankle as strongly because the intense focus is serving to narrow the gate.

Mechanisms and Theories Explaining How Exercise Reduces Pain

Exercise might reduce the experience of pain through physiological mechanisms including increases in beta-endorphins, serotonin, and endocannabinoids (eCB); increases in activation of eCB receptors; and reductions in inflammation (Lima et al., 2017). Beta-endorphins and serotonin are increased in response to both acute and chronic exercise. Beta-endorphins are endogenous opioids that are known to decrease substance P in the periphery. As previously explained, substance P is a neuropeptide involved in the pain response (e.g., a decrease in substance P would result in a dampening of the pain experience). Evidence also suggests that increases in serotonin and beta-endorphins in response to exercise interact to promote the reduction of pain. Another pathway by which exercise can reduce pain is through its impact on eCB receptors. These receptors are present in areas of the brain and spinal cord responsible for pain modulation, and these receptors are activated by exercise. When these receptors are activated, an analgesic (pain-reducing) effect is experienced. Circulating levels of eCBs are also increased in response to both aerobic exercise and resistance training, and these work synergistically with opioids to reduce the sensation of pain. With respect to inflammation and specific to migraine headaches, numerous inflammatory markers are implicated in the experience of migraines, and exercise has been shown to lead to a reduction in these inflammatory markers (Song and Chu, 2021). All of these mechanisms can play a role in the pain-reducing effects of exercise.

Think about the times when you have experienced pain. It is likely that you have experienced many different kinds of pain: acute pain such as from a paper cut or your leg falling asleep, or longer-term pain such as a headache, broken bone, or pain experienced following a surgery. Think about exercise relative to these experiences. In which cases do you think exercise is likely to be the most beneficial? This might be prior to the insult or following the insult. In other words, exercise might reduce your frequency of headaches in advance of the experience or if you can exercise while you have a headache, it might go away faster. Consider your choices with respect to exercise and whether you use exercise as a way to reduce pain perceptions.


Treatments for pain have been developed based on theory and an understanding of the mechanisms of pain. When considering treatments, we have to recognize that their efficacy is likely to differ depending on the nature of the pain. Many techniques that are used to manage pain are primarily effective with acute pain, and some should only be used for a limited period of time. For example, pharmacological interventions should only be used for relatively short periods of time because they can have potential damaging effects (e.g., liver failure, ulcers, anemia) or because they can become addictive (e.g., opioids). That said, pharmacological treatments play an important role in pain management for both acute and chronic pain.


Cupping is the practice of heating a glass and then putting it on your skin to reduce the sensation of pain from other sources. As the glass cools, a vacuum is created that pulls the skin up into the cup and bruises it. Olympic athletes have taken to using this technique as evidenced from images of swimmers at the 2016 Olympics including Michael Phelps. The mechanisms underlying its effectiveness aren’t clear. It might be effective because it closes the pain gate as in the gate control theory. Alternatively, it might increase blood flow to promote healing and it might break down chemical toxins that delay healing.


Transcutaneous electrical nerve stimulation (TENS) is the process of putting electrodes on the skin near where a person is experiencing pain and then giving a mild electric current. TENS use is predicated on the gate theory of pain, but it is also expected to have an impact on beta-endorphins. This treatment has been popular since the 1970s, but empirical evidence in support of this method is mixed and might depend on the particular context of use. For instance, Brosseau and colleagues (2002) reviewed a small number of studies (n = 3) looking at the effectiveness of TENS in lower back pain. Although none of the results were statistically significant (likely due to the small number of participants in each study), the TENS group reported reductions in pain intensity, improved functional status, and greater patient satisfaction as compared to a sham treatment group. More recently, results from a systematic review support positive effects compared to placebo treatments for patients experiencing acute pain when TENS was administered by ambulance staff (Simpson et al., 2014). Overall, TENS continues to be used to reduce pain, but empirical evidence supporting its efficacy is limited.

Other physical methods of pain management include the use of biofeedback, general relaxation, and acupuncture. Biofeedback is particularly effective with muscle tension headaches. When using biofeedback, a person is trained to reduce muscle tension through monitoring and responding to feedback provided by electrodes placed on the muscles suspected of being the root cause of the headaches. By gaining an awareness of the existing muscle tension and learning techniques to reduce muscle tension, patients ultimately can gain some control over their headaches. General relaxation also might be effective and is a less expensive therapy because it can be learned without equipment. Acupuncture is another treatment that has been used effectively to control pain. Acupuncture, or the use of small needles to stimulate specific places in the body, has been used in traditional Chinese medicine for over 3,000 years. In 1976, acupuncture needles were approved by the United States Food and Drug Administration as medical devices for general use. Recent evidence supports its effectiveness in reducing pain from chronic musculoskeletal pain (e.g., low back, neck, shoulder, knee), headache, and arthritis as compared to sham acupuncture (ES = 0.20) and no acupuncture (ES = 0.50) controls (Vickers et al., 2018). According to traditional Chinese medicine, acupuncture is effective when used at one of the 365 meridians in the body to release qi and thus restore balance between yin and yang, which are the two interrelated forces that are foundational to Eastern medicine. Researchers from Western countries have attempted to identify physiological mechanisms to explain the benefits of acupuncture. In brief, Western researchers believe that acupuncture works because the needles stimulate both local and central pain-control mechanisms (Coutaux, 2017).

Many pharmacological interventions are effective for reducing the experience of pain. Peripherally acting analgesics (pain relievers) work by inhibiting the production of the neurochemicals that are needed for the nociceptors to sense the release of algogenic substances. Hence, these painkillers stop the signal right at its source. Examples of this type of pain reliever include acetaminophen and nonsteroidal anti-inflammatories (NSAIDs). These pain relievers are systemic in that they are typically taken orally and can reduce pain anywhere in the body. Because of the mechanism of action, NSAIDS also reduce inflammation. Local anesthetics are used to block the afferent nerve cells from generating impulses to deliver to the spinal cord. As you might guess, local anesthetics result in pain relief in a localized area. Examples of these include morphine, Novocain, and lidocaine, which are used for relatively minor surgical procedures such as having a cavity filled. Regional anesthetics can be used to block pain sensations in a larger region of the body. For example, an epidural is when pain medicine is injected into the fluid around the spine; some women request an epidural when giving birth. This regional pain medicine provides relief, but the person remains conscious. Centrally acting analgesics affect the entire body. Examples include codeine and morphine, which would be used for major surgeries where the pain is likely to be more severe and pervasive, as with spinal surgery.

Another method of pain management is to perform surgery to intervene when there is a physical cause for the pain. This is used in many situations such as to stop a toothache (e.g., removing decay and filling a cavity), to alleviate back pain (e.g., discectomy for a herniated disk), or to treat arthritis (e.g., a synovectomy to remove membranes that line a joint to reduce inflammation). These surgical methods can provide relief that can be temporary or permanent, and people tend to recover fairly quickly and manage postoperative pain using the pharmacological interventions previously discussed.

Additionally, numerous cognitive methods can be used to help control the experience of pain. These are most effective for acute forms of pain that are mild to moderate in terms of their severity. When using these methods, a person focuses on something in the environment that is nonpainful and that can serve as a distraction. An example is listening to music while at the dentist or focusing on a picture of the baby’s ultrasound during labor. Another example is using mental imagery to visualize a relaxing and peaceful scene that serves as a means of distraction from the source of the discomfort. Coping statements also can be effective, such as saying to oneself, “I can endure” or “It’s not that bad.”