Causes of pain
The pain reaction in the body is triggered under the influence of two key factors that threaten tissue viability.
The first factor is breach of the integrity of protective integuments. Any damage to membranes poses a threat to homeostasis (constancy of the internal environment). In this case, pain performs a crucial monitoring function. It acts as a strong negative biological drive, which creates motivation for a person to get rid of the source of pain as quickly as possible.
The second factor is changes in the level of oxygen metabolism. Pain occurs when oxidative processes are disrupted or normal blood access to tissues ceases (ischemia or hypoxia develops). The body reacts to this systemically: the autonomic nervous system is activated, predominantly its sympathetic division. This is strongly compensatory in nature, as sympathetic stimulation aims to improve oxygen supply to the affected organ and restore tissue trophism (nutrition).
General principles of nociception
In physiology, there is the "specificity" theory, according to which pain is perceived by special receptors — nociceptors. Structurally, they form plexiform networks in the skin, muscles, and some internal organs.
A crucial feature of pain sensitivity is the mismatch between the excitation of a single receptor and the actual sensation of pain. A single impulse is not enough. According to the "intensity" theory, for a person to feel pain, multiple excitations of numerous receptors are necessary. The pain sensation is always the result of spatial and temporal summation of sensory irritations from a strong impact.
Classification: Mechanonociceptors (Type I)
According to L.N. Smolin's classification, the first type of pain receptors is mechanonociceptors. Their membrane depolarizes exclusively as a result of mechanical displacement. They are localized in integumentary membranes, deep tissues, visceral organs, and vessel walls. Their main function is monitoring tissue integrity.
Several groups of mechanonociceptors are distinguished:
- Cutaneous with Aδ-fiber afferents. They respond only to mechanical stimuli, ignoring heat and chemistry. They feature narrow receptive fields and rapid adaptation. They are responsible for epicritic (primary, sharp) pain.
- Epidermal with C-fiber afferents. Also activated only mechanically, unresponsive to temperature fluctuations. They have narrow fields and adapt easily.
- Muscular with Aδ-fiber afferents. Located on the surface of muscles and at the transition sites into tendons. Excited by heavy pressure from blunt objects. Adapt rapidly.
- Articular with Aδ-fiber afferents. Located in joint capsules. Activated only under extreme conditions: during excessive flexion or unnatural twisting of the joint.
Classification: Polymodal C-nociceptors (Type II)
The second type of receptors is excited by the action of a whole complex of strong stimuli: mechanical, thermal, and chemical. They respond to substances that disrupt normal oxidative processes in tissues (histamine, acetylcholine, acid solutions). Signals from them are transmitted predominantly via C-fibers. The physiological role of this group is monitoring the respiratory function of tissues.
Polymodal receptors are divided into the following subgroups:
- Cutaneous (type 1): activated by a combination of mechanical stimulus and strong cooling (down to 15 °C).
- Cutaneous (type 2): respond to mechanical impact and severe heating. Unlike many other receptors, they adapt slowly.
- Subcutaneous: require simultaneous strong pressure on the skin and the administration of chemical substances.
- Muscular: respond to all types of stimuli, including specific chemical markers of inflammation (bradykinin, histamine).
- Receptors of internal parenchymal organs: localized mainly in the walls of small arterioles.
Briefly: answers to topical questions
What types of pain are distinguished by clinical and pathophysiological classification?
According to clinical and pathophysiological classifications, several main types of pain are distinguished.
- Somatic pain — subdivided into superficial (irritation of the skin) and deep (receptors of muscles, joints, tendons).
- Visceral pain — associated with diseases of internal organs.
- Nociceptive pain — arises in response to tissue damage and activation of pain receptors.
- Neuropathic pain — caused by damage to structures of the peripheral or central nervous system.
- Nociplastic pain — mentioned as a factor in complex regional pain syndrome.
In addition, by localization and character, epicritic, protopathic, phantom, and referred pain are distinguished, and by the time of formation — early and late.
Through which pathways is the pain impulse transmitted to the brain?
The transmission of the pain impulse to the brain is carried out predominantly via the spinothalamic tracts.
- Lateral spinothalamic tract (tractus spinothalamicus) — the main highway in the lateral funiculus of the spinal cord, whose fibers cross to the opposite side and carry impulses to the thalamus.
- Neospinothalamic pathway — conducts fast, localized pain to specific nuclei of the thalamus (VPL).
- Paleospinothalamic pathway — transmits slow, affective-motivational pain to non-specific (intralaminar, reticular) nuclei of the thalamus.
From the thalamic nuclei, the signal is transmitted to the cerebral cortex (in particular, to the postcentral gyrus) via the thalamocortical tract for final analysis.
Which neurotransmitters are involved in the synaptic transmission of the pain signal in the spinal cord?
A number of neurotransmitters are involved in the synaptic transmission and modulation of the pain signal in the spinal cord. The main excitatory ("nociceptive") pain mediators released at the level of the dorsal horns of the spinal cord include:
- Glutamate — the mediator of fast pain in the neospinothalamic pathway.
- Substance P (Substance P) — a neurokinin involved in the transmission of slow pain (paleospinothalamic pathway) and exerting a modulatory enhancing effect on the transmission of nociceptive impulses.
Additionally, modulators act at the first relay station: histamine, neurotensin, cholecystokinin, norepinephrine, serotonin, as well as inhibitory mediators — GABA and enkephalins, which suppress the pain signal.
What is the antinociceptive system and what endogenous substances are involved in it?
The antinociceptive system is a regulatory system that ensures the inhibition of the activity of nociceptive neurons at the levels of the dorsal horns of the spinal cord, the reticular formation of the brainstem, and the thalamus. Its function is to suppress pain impulses and provide pain relief.
The main endogenous substances of this system are opioid peptides:
- Endorphins — include $\alpha$-, $\beta$-, and $\gamma$-fractions.
- Enkephalins — have a wider localization in the central nervous system.
These neuropeptides bind to opiate receptors, inhibit the sensitivity of second-order neurons to pain mediators, and suppress their release, inducing a state of hypoalgesia or analgesia.
To not confuse fibers: Aδ-fibers (A-delta) mean Attack (mechanical displacement) and Acute (sharp, primary, epicritic pain). C-fibers mean Composite (polymodal: gathering all stimuli — mechanical, thermal, chemical).
Class and exam questions
Does the excitation of a single nociceptor cause a feeling of pain?
No, there is a discrepancy between the excitation threshold of an individual receptor and the perception of a sensation. Pain occurs only as a result of the summation of multiple sensory stimuli.
Which chemical substances are capable of exciting polymodal C-nociceptors?
Such stimuli include solutions of acids (sulfuric, acetic, hydrochloric), acetylcholine, histamine, and bradykinin, which disrupt oxidative processes in tissues.
Why is the sympathetic nervous system activated during tissue ischemia?
This is a compensatory reaction of the body to oxygen deprivation. Activation of the sympathetic division of the autonomic nervous system helps improve blood supply to the affected organ and restore tissue trophism.
What else to study on this topic
- Morphological structure of plexiform plexuses of free nerve endings
- Receptor adaptation mechanisms: the difference between rapid and slow adaptation of nociceptors
- Characteristics of pain impulse conduction along Aδ- and C-fibers
- Intensity theory and processes of spatiotemporal pain summation
- The role of the autonomic nervous system in compensating for tissue hypoxia during pain syndrome
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