The mechanism by which pain occurs is not fully understood. It is generally believed that nerve endings (injurious receptors) are exposed to various injurious stimuli (physical or chemical) and are transmitted to the brain through the conduction system (spinal cord), which causes pain sensation. At the same time, the central nervous system has a regulatory role in the occurrence and development of pain.
I. Injury receptors
Injury receptors include the free end of sensory nerves, terminal nerve vesicles and terminal axons without sheaths. According to the distribution of the body and the different stimuli received, the injury receptors can be divided into skin, muscle, joint and visceral injury receptors. From these receptors, the received stimuli are transmitted to the spinal cord, which in turn transmits to the brain through the upstream conduction bundle to form pain sensation.
II. Pain
Conduction at the terminals Pain is transmitted through fine myelinated Aa and unmyelinated C-conducting nerve fibers.
The myelinated A. fibers are fast and conduct pinpoint stabbing pain and temperature sensation; the unmyelinated C fibers are slow and conduct dull pain and burning pain. Pain is transmitted through Aa and C fibers to T cells in the posterior horn of the spinal cord, and the excited T cells then transmit pain to the brain through the thalamic tract of the spinal cord.
The thick nerve fibers do not directly transmit nociception, but the impulses transmitted by them can inhibit nociceptive transmission to the center through a “gate” mechanism. In addition, the pain-related downstream inhibitory pathway from the brainstem reticular formation, mainly through the interseptal nucleus producing 5HT, and the reticular formation producing enkephalins and endorphins, weakens the afferent signal from the posterior horn of the spinal cord.
III. Pain transmission in the center
There are two main pathways.
1.Through the thalamic tract of the spinal cord to the thalamus and then gradually to the brain layer, so that the body perceives the presence or absence of pain and the site of occurrence;
2. The spinal reticular system transmits to the brainstem reticular formation, the lower thalamus and the limbic system of the brain, causing the body’s emotional response to painful stimuli and the response of the autonomic nervous system.
IV. Pain perception and recognition
After pain impulses are transmitted to the center, their perception and recognition need to be integrated and analyzed. Among them, the central gyrus is responsible for perceiving the site of pain; the reticular formation, the limbic system, the frontal, parietal, temporal lobes and other extensive cerebral cortex are responsible for the integrated analysis and the emotional response to pain and the issuance of reflexive or conscious movements. i In addition to the above pain mechanisms, recent studies have shown that peripheral sensitization and central sensitization processes play an important role in the mechanism of pain onset.
1. Peripheral sensitization
During tissue injury and inflammatory response, cells at the damaged site, such as mast cells, macrophages and lymphocytes, release a variety of inflammatory mediators. Also, the injurious stimulus itself can lead to a neurogenic inflammatory response that further promotes the release of inflammatory mediators. These factors make it possible to cause pain even with low-intensity subthreshold stimuli, which is the process of “peripheral sensitization”.
Peripheral sensitization can occur as follows.
(1) resting pain or spontaneous pain: nociception in the absence of peripheral injurious stimuli, caused by the voluntary activation of peripheral injurious receptors;
(2) Primary nociceptive hyperalgesia: pain is intense in spite of mild painful stimuli, due to overreaction of receptors to injurious stimuli;
(3) abnormal pain: pain can be caused by non-injurious stimuli such as light pressure.
2.Central sensitization
After tissue injury, not only the response of the injured area to normal harmless stimuli is enhanced, but also the response of the uninjured area in the adjacent parts to mechanical stimuli is enhanced, which is called secondary nociceptive sensitization. This is due to the plasticity of the central nervous system after the onset of pain, and the excitability of the dorsal horn neurons of the spinal cord is increased, showing an “upward” effect, that is, the central sensitization process.
During pain transmission, many neurotransmitters act on various receptors in the spinal cord. Among them, NMDA receptors are closely related to the effect of the dorsal horn of the spinal cord, the occurrence of central sensitization, and the expansion of peripheral sensory areas.