The nociceptive system and its receptors
The pain perception system is sometimes called the pain analyzer, although in modern physiology this term is not entirely correct. Nevertheless, its structure corresponds to the general plan of an analyzer: receptor component, pathways, and cortical component.
Pain receptors — nociceptors — are free nerve endings, meaning unencapsulated dendrite terminals (unlike encapsulated Vater–Pacini or Meissner corpuscles). The cell bodies of the corresponding sensory neurons are located in the spinal ganglion.
According to the stimulus modality, nociceptors are divided into:
- mechanoreceptors — respond to mechanical stimuli;
- thermoreceptors — to temperature changes;
- chemoreceptors — to chemical agents;
- polymodal — perceive multiple types of stimuli simultaneously.
Pain sensations can also occur with excessive stimulation of receptors of other modalities (e.g., photoreceptors in bright light).
Pain sensitivity pathways
The impulse from nociceptors can travel via two pathways.
- Fast pathway — via myelinated A-delta fibers. The impulse enters the spinal ganglion, then ascends as part of the superficial and deep sensitivity pathways to the thalamus, and from there to the postcentral gyrus of the parietal lobe. This pathway provides precise pain localization.
- Slow pathway — predominantly via unmyelinated C fibers (less commonly A-delta). The impulse travels through the spinal ganglion to the reticular formation, then to the thalamus, and subsequently spreads diffusely across all cortical areas, forming the emotional and autonomic components of pain.
Impulse transmission in the synapses of the nociceptive system is mediated by: glutamate and substance P.
Causes and mechanisms of pain
The leading cause of pain, especially visceral, is ischemia. It can develop as a result of:
- vascular spasm;
- spasm or distension of a hollow organ;
- vascular occlusion.
During ischemia, blood supply is disrupted, underoxidized metabolic products accumulate, and bradykinin, kallidin, and prostaglandins are released. These substances activate chemoreceptors and polymodal nociceptors, generating a pain impulse.
Important clinical feature: there are no nociceptors in the parenchyma of internal organs (liver, spleen, kidney) — they are located in the organ capsule, serous membranes, and vascular walls. Therefore, parenchymal damage can be painless. Similarly, there are no receptors inside bone tissue; pain sensations are generated when the periosteum is irritated.
Pharmacological principles of analgesia
Prostaglandins are formed from arachidonic acid with the participation of the enzyme cyclooxygenase (COX). They maintain inflammation and sensitize nociceptors. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit COX, reducing prostaglandin synthesis, which decreases inflammation and pain signaling. This is the basic mechanism of action of most analgesic-antipyretic drugs.
Pain Classification
Pain is classified according to several criteria.
By the nature of the course:
- acute;
- chronic.
By localization:
- superficial somatic — from skin receptors;
- deep somatic — from muscles, tendons, meninges;
- visceral — from internal organs.
By the mechanism of origin and propagation:
- local — in the area of direct action of the stimulus;
- referred — occurs in skin areas during internal organ pathology; the mechanism is associated with the convergence of visceral and somatic afferents on a single spinal neuron (e.g., pain in the left arm and scapula in heart disease);
- projected — when a nerve trunk is irritated, pain is felt in its innervation zone;
- radiating — spreads from one nerve branch to another (e.g., between the branches of the trigeminal nerve);
- phantom — felt in a missing amputated limb, associated with scarring of nerve endings in the stump;
- causalgia — burning pain upon nerve trunk damage;
- psychogenic — without a clear organic substrate.
Key points
- Nociceptors are free nerve endings, neuron cell bodies lie in the spinal ganglion.
- There are mechanoreceptors, thermoreceptors, chemoreceptors, and polymodal nociceptors.
- Fast pain is conducted via A-delta fibers to the postcentral gyrus, slow pain via C fibers through the reticular formation to all cortical areas.
- The neurotransmitters of nociceptive synapses are glutamate and substance P.
- The main cause of visceral pain is ischemia with the accumulation of bradykinin, prostaglandins, and underoxidized products.
- There are no nociceptors in the parenchyma of internal organs and inside bone; pain is generated upon irritation of the capsule, serosa, or periosteum.
- NSAIDs reduce pain by inhibiting COX and decreasing prostaglandin synthesis.
- Distinctions are made among local, referred, projected, radiating, phantom, causalgic, and psychogenic types of pain.