In this blog post, we will learn about the physiological principles of pain, the process of nerve transmission, and the defensive role and inhibitory mechanism of pain.
Pain is a type of sensation that acts as a defense mechanism, giving us conscious awareness when tissue damage occurs or is about to occur. Stimuli that cause pain include mechanical stimuli caused by strong physical impact, stimuli caused by high temperatures, and chemical stimuli caused by chemicals released from cells when they are injured or infected by microorganisms. These stimuli are received by the sensory nerves spread throughout the body, which are called pain receptors. Pain receptors are most abundant in the skin, so pain originating in the skin is easy to locate, but pain originating in internal organs, where there are few pain receptors, is difficult to locate precisely. For example, pain felt in the digestive organs generally feels more diffuse, making it difficult to identify the exact cause. This is because visceral pain often spreads to other parts of the internal organs or causes referred pain.
Sensory adaptation occurs in sensory receptors such as olfactory and tactile receptors, in which the response of the receptor decreases in response to continuous stimulation. However, sensory adaptation rarely occurs in pain receptors in response to continuous stimulation. This allows our bodies to respond to dangerous situations. For example, when you sprain your ankle, you feel intense pain at first, but after a while, the pain seems to dull or subside. However, this is not because the response to the pain stimulus has decreased. Rather, this pain triggers various physiological responses in the body to protect the injured area and promote healing.
Typical pain-sensing nerve fibers include Aδ fibers and C fibers. Aδ fibers contain pain receptors that respond to mechanical stimuli and high temperatures, while C fibers contain pain receptors that respond not only to mechanical stimuli and high temperatures but also to chemical stimuli. When pain signals conducted along Aδ fibers are transmitted to the cerebral cortex, the cerebral cortex senses a sharp, stinging, short initial pain and locates the source of the pain. When pain signals conducted along C fibers are transmitted to the cerebral cortex, the cerebral cortex senses a throbbing, dull, delayed pain. This is related to the characteristics of the two nerve fibers. Aδ fibers have a large diameter and fast conduction speed, while C fibers have a small diameter and slow conduction speed. The transmission of pain signals originating in the lower part of the head is accomplished by the conversion of stimuli received by nociceptors into electrical signals, which are then conducted along primary nerve fibers connected to the nociceptors and transmitted along secondary nerve fibers originating in the spinal cord to the thalamus and then to the central brain.
Primary and secondary nerve fibers form synapses in the spinal cord, and neurotransmitters must be secreted from the primary nerve fibers in order for pain signals to be transmitted. The neurotransmitter glutamate is secreted from the terminals of the primary nerve fibers and binds to AMPA receptors and NMDA receptors in the secondary nerve fibers, activating the receptors. However, NMDA receptors are inhibited by magnesium ions, so only AMPA receptors are activated first by small amounts of glutamate. When AMPA receptors are activated, sodium ions flow into the secondary nerve fibers, and pain signals conducted along the primary nerve fibers are transmitted to the secondary nerve fibers. The pain signals are then transmitted to the cerebral cortex via the thalamus. When sodium ions enter through AMPA receptors, NMDA receptors are also activated, allowing calcium ions to enter as well as sodium ions. In this case, the calcium ions prevent pain signals from being transmitted to the cerebral cortex, but they increase the sensitivity of the pain receptors, causing them to react sensitively even to weak stimuli.
The neurotransmitter substance P is secreted from the terminals of primary nerve fibers and activates NK receptors in secondary nerve fibers, transmitting pain signals to secondary nerve fibers. Pain signals pass through the thalamus to the cerebral cortex, causing pain, and are transmitted to the limbic system, which includes various parts of the brain such as the reticular formation and hypothalamus, stimulating the autonomic nervous system and endocrine system to cause behavioral and emotional responses to pain. Pain signals also trigger emotional responses and play an important role in regulating an individual’s experience of pain and response to it. This means that pain goes beyond the simple transmission of nerve signals and plays an important role on a psychological and emotional level.
Meanwhile, nerve fibers extending from the reticular formation to the terminals of primary nerve fibers secrete analgesic neurotransmitters such as endorphins, enkephalins, and dynorphins. These substances bind to opioid receptors at the terminals of primary nerve fibers, inhibiting the release of substance P from the primary nerve fibers and preventing pain signals from being transmitted to the secondary nerve fibers. This pain inhibition system plays a role in alleviating or preventing the sensation of pain in situations where the body has suffered trauma, making it possible to endure pain. For example, in situations where one must fight for survival even while injured, pain is temporarily alleviated, enabling the necessary actions to be taken. This system is also important for patients with chronic pain, as chronic pain can reduce quality of life due to continuous pain signals, making proper pain management and inhibition essential.
