PAIN: PHYSIOLOGY, BRAIN PROCESSES AND RECEPTORS - GEOGRAFÍA - 2025

The pain is a phenomenon that indicates that some part of our body is suffering damage. It is characterized by a withdrawal response from the factor that is causing it; for example, removing your hand from something that burns, although in humans it can be known by verbalizations.

Pain has a protective function for our body, as occurs for example with pain from inflammation. The inflammation is often accompanied by damage to the skin and muscles.

Thus, the sensitivity of the inflamed part to painful stimuli is greatly intensified; This causes movements with the affected area to be reduced and contact with other objects is avoided. Ultimately, the mission of inflammation is to try to reduce the likelihood of new injuries and speed up the recovery process.

Those born with reduced sensitivity to pain suffer more injuries than usual, such as burns and cuts. They can also adopt positions that are harmful to the joints, but because they do not feel pain, they do not change position.

The absence of pain can have very serious health consequences, and can even lead to death. Pain perception analysis is extremely complicated. However, you can try to explain yourself simply.

The painful stimulus activates the pain receptors. The information is then transmitted to specialized nerves in the spinal cord to eventually reach the brain. Once processed there, this organ sends an impulse that forces the body to react. For example, quickly removing your hand from a hot object.

Awareness of pain and the emotional reaction it causes is controlled in the brain. Stimuli that tend to produce pain also elicit a withdrawal or flight response. Subjectively, something that causes pain is annoying and harmful. That is why we actively avoid it.

The three elements of pain

It is true that some environmental events can modulate the perception of pain. For example, a study by Beecher (1959) analyzed the pain response of a group of American soldiers who fought during World War II.

It was shown that a large part of the American soldiers who had suffered injuries in battle did not appear to show signs of pain. In fact, they did not need medication. Apparently, the perception of pain was reduced in them as they felt the relief that they had managed to survive the battle.

It can also happen that the pain is perceived, but it does not seem relevant to the person. Some tranquilizing drugs have this effect, as do some lesions in specific parts of the brain.

Lobes of the human brain. Source: Jkwchui / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)

Pain has three different effects on perception and behavior.

- The sensory aspect. It refers to the perception of the intensity of the painful stimulus.

- The direct emotional consequences that pain produces. That is, the degree of discomfort that this pain causes in the person. This is the component that decreases in wounded soldiers who survived the battle.

- The long-term emotional involvement of pain. This effect is the product of conditions associated with chronic pain. Specifically, it is about the threat that this pain poses to our future well-being.

Pain physiology

The three previous elements involve different brain processes. The purely sensory component is regulated in the pathways from the spinal cord to the ventral posterior nucleus of the thalamus. Eventually, they reach the primary and secondary somatosensory cortex of the brain.

The immediate emotional component seems to be controlled by pathways that reach the anterior cingulate cortex and the insula. It has been shown in various studies that these areas are activated during the perception of painful stimuli. Furthermore, electrical stimulation of the insular cortex has been found to cause stinging or burning sensations in subjects.

In conclusion, the primary somatosensory cortex is responsible for perceiving pain, while the anterior cingulate processes the immediate emotional effects. On the other hand, the long-term emotional component is mediated by connections that reach the prefrontal cortex.

People with damage to this area feel apathetic and tend not to be affected by the consequences of chronic diseases, including chronic pain.

Types of pain receptors

Source; Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2).

Pain receptors are free nerve endings. These receptors are present throughout the body, especially in the skin, on the surface of the joints, in the periosteum (membrane that covers the bones), the walls of the arteries, and some structures of the skull.

Interestingly, the brain itself does not have any pain receptors, therefore it is insensitive to pain.

Pain receptors respond to three types of stimuli: mechanical, thermal, and chemical. A mechanical stimulus would be putting pressure on the skin (for example). While a thermal stimulus, heat or cold. A chemical stimulus is an external substance, like an acid.

Pain receptors can also be stimulated by chemicals in the body. They are released as a result of trauma, inflammation, or other painful stimuli. An example of this is serotonin, potassium ions or acids such as lactic acid. The latter is responsible for muscle pain after exercising.

There are three types of pain receptors, also called nociceptors or noxious stimulus detectors.

High-threshold mechanoreceptors

They are free nerve endings that respond to strong pressure such as a blow or squeeze on the skin.

VR1 receivers

The second type consists of nerve endings that capture extreme heat, acids, and capsaicin (the active ingredient in hot peppers). The receptors of this type of fiber are known as VR1. This receptor is involved in pain associated with inflammation and burns.

In fact, it was shown in a study that mice that had a mutation against the expression of this receptor, could drink water with capsaicin. Since they seemed insensitive to high temperatures and spicy, although they reacted to other painful stimuli. Caterina et. to the. (2000).

ATP-sensitive receptors

ATP is the fundamental energy source for the metabolic processes of cells. This substance is released when blood circulation to a part of the body is interrupted or when a muscle is injured. It is also produced by rapidly developing tumors.

Therefore, these receptors may be responsible for pain associated with migraine, angina, muscle injury, or cancer.

Types of pain

The impulses originating in pain receptors are transmitted to the peripheral nerves through two nerve fibers: the A delta fibers, which are responsible for fast (primary) pain, and the C fibers that transmit slow (secondary) pain.

When we perceive a painful stimulus we have two sensations.

Quick pain

The first one is "quick pain". It is experienced as a sharp, stabbing and very localized pain. This activates protective mechanisms such as the withdrawal reflex.

The delta A fibers that transmit this type of pain are microscopically thinner (2 to 5 thousandths of a millimeter). This allows the stimulus to be transmitted faster (5 to 30 meters per second).

In rapid pain it is localized and does not spread. It is difficult to overcome, even with strong pain relievers.

Slow pain

After a few seconds of feeling the fast pain, the "slow pain" appears. It is persistent, deep, opaque and less localized.

It usually lasts a few days or weeks, although if the body does not process it properly, it can last longer and become chronic. This type of pain is intended to activate the tissue repair process.

The C fibers that transmit this kind of pain have a greater diameter than the delta A fibers (between 0.2 and 1 thousandth of a millimeter). That is why the impulse is slower (speed of 2 meters per second). The body's response is to hold the affected part immobile, leading to spasms or stiffness.

Opioids are very effective in slow pain, but so are local anesthetics if the appropriate nerves are blocked.

Why does analgesia occur?

When living beings have to face a harmful stimulus, they usually interrupt what they are doing to initiate withdrawal or escape behaviors. However, there are times when this reaction is counterproductive. For example, if an animal has a wound that causes pain, flight responses can interfere with daily activities, such as eating.

Therefore, it would be more convenient if chronic pain could be reduced. Analgesia also serves to decrease pain during the performance of biologically important behaviors.

Pairing example

Some examples are fighting or mating. If pain were experienced at this time, the survival of the species would be in danger.

For example, some studies have shown that copulation can cause analgesia. This has an adaptive meaning, since painful stimuli during copulation would be felt to a lesser extent so that reproductive behavior is not interrupted. This increases the probability of reproduction.

Rats

It has been shown that when rats receive painful electrical shocks that they cannot avoid, they experience analgesia. That is, they had less sensitivity to pain than control subjects. This is produced by the release of opioids dictated by the body itself.

Ultimately, if it is understood that pain is inevitable, analgesic mechanisms are activated. Whereas, if it is avoidable, the subject is motivated to give the appropriate responses to interrupt that pain.

Ways to avoid physical pain

Pain can be reduced if areas other than those affected are stimulated. For example, when a person has a wound they feel some relief if they scratch around it.

That is why acupuncture uses needles that are inserted and twisted to stimulate nerve endings near and far away from those where pain is reduced.

Some studies have proven that acupuncture produces analgesia due to the release of endogenous opioids. Although pain reduction may be more effective if the person "believes" in its effects, this is not the only reason.

Animal studies have shown a reduction in pain sensitivity. As well as the activation of Fos proteins in the somatosensory neurons of the dorsal horn of the spinal cord.

References

1. Basbaum, AI, Bautista, DM, Scherrer, G., & Julius, D. (2009). Cellular and molecular mechanisms of pain. Cell, 139 (2), 267-284.
2. Beecher, HK (1959). Measurement of subjective responses: quantitative effects of drugs. New York: Oxford University Press.
3. Carlson, NR (2006). Physiology of behavior 8th Ed. Madrid: Pearson.
4. Mayer, DJ, & Liebeskind, JC (1974). Pain reduction by focal electrical stimulation of the brain: an anatomical and behavioral analysis. Brain research, 68 (1), 73-93.
5. National Research Council (US) (2010). Recognition and alleviation of pain in laboratory animals. Washington (DC): National Academies Press (US).
6. Rainville, P., Duncan, GH, Price, DD, Carrier, B., & Bushnell, MC (1997). Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science, 277 (5328), 968-971.
7. Stucky, CL, Gold, MS, & Zhang, X. (2001). Mechanisms of pain. Proceedings of the National Academy of Sciences, 98 (21), 11845-11846.