Pathways of pain and its mechanisms. Pain receptors. Nociceptive sensitivity and its physiological role. Projection and referred pain Pain. Pain sensitivity. Nociceptors. Pathways of pain sensitivity. Pain assessment. Gate of pain. Opiate

Pain is a symptom of many diseases and injuries to the body. A person has developed a complex mechanism for the perception of pain, which signals damage and forces one to take measures to eliminate the causes of pain (pulling the hand, etc.).

Nociceptive system

The so-called nociceptive system. In a simplified form, the mechanism of pain can be represented as follows (Figure ⭣).

When pain receptors (nociceptors) are irritated, localized in various organs and tissues (skin, blood vessels, skeletal muscles, periosteum, etc.), a flow of pain impulses occurs, which travel through afferent fibers to the dorsal horns of the spinal cord.

Afferent fibers are of two types: A-delta fibers and C-fibers.

A-delta fiber are myelinated, which means they are fast-conducting - the speed of impulses through them is 6-30 m/s. A-delta fibers are responsible for transmitting acute pain. They are excited by high-intensity mechanical (pinprick) and sometimes thermal irritations of the skin. They rather have an informational value for the body (they force you to withdraw your hand, jump away, etc.).

Anatomically, A-delta nociceptors are represented by free nerve endings, branched in the form of a tree. They are located primarily in the skin and at both ends of the digestive tract. They are also found in the joints. The transmitter (nerve signal transmitter) of A-delta fibers remains unknown.

C-fibers- unmyelinated; they conduct powerful but slow impulse flows at a speed of 0.5-2 m/s. These afferent fibers are thought to be dedicated to the perception of secondary acute and chronic pain.

C-fibers are represented by dense, non-encapsulated glomerular bodies. They are polymodal nociceptors, therefore they respond to both mechanical and thermal and chemical stimuli. They are activated by chemicals that occur during tissue damage, being at the same time chemoreceptors, they are considered optimal tissue-damaging receptors.

C-fibers are distributed throughout all tissues with the exception of the central nervous system. Fibers that have receptors that sense tissue damage contain substance P, which acts as a transmitter.

In the dorsal horns of the spinal cord, the signal switches from the afferent fiber to the interneuron, from which, in turn, the impulse branches off, exciting motor neurons. This branch is accompanied by a motor reaction to pain - withdrawing the hand, jumping away, etc. From the interneuron, the flow of impulses, rising further through the central nervous system, passes through the medulla oblongata, which contains several vital centers: respiratory, vasomotor, vagus nerve centers, cough center, vomiting center. That is why pain in some cases has vegetative accompaniment - heartbeat, sweating, surges in blood pressure, salivation, etc.

Next, the pain impulse reaches the thalamus. The thalamus is one of the key links in pain signal transmission. It contains the so-called switching (SNT) and associative nuclei of the thalamus (AT). These formations have a certain, fairly high threshold of excitation, which not all pain impulses can overcome. The presence of such a threshold is very important in the mechanism of pain perception; without it, any slightest irritation would cause a painful sensation.

However, if the impulse is strong enough, it causes depolarization of the PAT cells, impulses from them enter the motor areas of the cerebral cortex, determining the very sensation of pain. This path of pain impulses is called specific. It provides a pain signaling function - the body perceives the occurrence of pain.

In turn, activation of the AYT causes impulses to enter the limbic system and hypothalamus, providing an emotional coloring of pain (a nonspecific pain pathway). It is because of this pathway that the perception of pain has a psycho-emotional connotation. In addition, thanks to this pathway, people can describe the perceived pain: sharp, throbbing, stabbing, aching, etc., which is determined by the level of imagination and the type of nervous system of the person.

Antinociceptive system

Throughout the nociceptive system there are elements of the antinociceptive system, which is also an integral part of the mechanism of pain perception. The elements of this system are designed to suppress pain. The mechanisms of analgesia development, controlled by the antinociceptive system, involve the serotonergic, GABAergic and, to the greatest extent, the opioid system. The functioning of the latter is realized due to protein transmitters - enkephalins, endorphins - and opioid receptors specific to them.

Enkefapins(met-enkephalin - H-Tyr-Gly-Gly-Phe-Met-OH, leu-enkephalin - H-Tyr-Gly-Gly-Phe-Leu-OH, etc.) were first isolated in 1975 from the brain of mammals . According to their chemical structure, they belong to the class of pentapeptides, having a very similar structure and molecular weight. Enkephalins are neurotransmitters of the opioid system, functioning throughout its entire length from nociceptors and afferent fibers to brain structures.

Endorphins(β-endophin and dynorphin) are hormones produced by corticotropic cells of the middle lobe of the pituitary gland. Endorphins have a more complex structure and larger molecular weight than enkephalins. Thus, β-endophin is synthesized from β-lipotropin, being, in fact, the 61-91 amino acid part of this hormone.

Enkephalins and endorphins, stimulating opioid receptors, carry out physiological antinociception, and enkephalins should be considered as neurotransmitters, and endorphins as hormones.

Opioid receptors- a class of receptors that, being targets for endorphins and enkephalins, are involved in the implementation of the effects of the antinociceptive system. Their name comes from opium - the dried milky juice of the sleeping pill poppy, known since ancient times as a source of narcotic analgesics.

There are 3 main types of opioid receptors: μ (mu), δ (delta), κ (kappa). Their localization and the effects that occur when they are excited are presented in table ⭣.

Enkephalins and endorphins, stimulating opioid receptors, cause activation of the G₁ protein associated with these receptors. This protein inhibits the enzyme adenylate cyclase, which under normal conditions promotes the synthesis of cyclic adenosine monophosphate (cAMP). Against the background of its blockade, the amount of cAMP inside the cell decreases, which leads to activation of membrane potassium channels and blockade of calcium channels.

As you know, potassium is an intracellular ion, calcium is an extracellular ion. These changes in the functioning of ion channels cause the release of potassium ions from the cell, while calcium cannot enter the cell. As a result, the membrane charge decreases sharply, and hyperpolarization develops - a condition in which the cell does not perceive or transmit excitation. As a consequence, suppression of nociceptive impulses occurs.

Sources:
1. Lectures on pharmacology for higher medical and pharmaceutical education / V.M. Bryukhanov, Ya.F. Zverev, V.V. Lampatov, A.Yu. Zharikov, O.S. Talalaeva - Barnaul: Spektr Publishing House, 2014.
2. General human pathology / Sarkisov D.S., Paltsev M.A., Khitrov N.K. - M.: Medicine, 1997.

Somatic and visceral sensitivity

Sensory sensations are divided into 3 physiological classes: mechanoreceptive, temperature And painful. Mechanoreceptive sensations include tactile(touch, pressure, vibration) and proprioceptive(postural) - a sense of posture, static position and position during movement.

According to the place where sensations arise, sensitivity is classified as exteroceptive(sensations arising from the surface of the body), visceral(sensations arising in the internal organs) and deep(sensations come from deep-lying tissues - fascia, muscles, bones).

· Somatic sensory signals transmitted with high speed, high accuracy of localization and determination of minimal gradations of intensity or changes in the strength of the sensory signal.

· Visceral signals are characterized by a lower conduction speed, a less developed system of spatial localization of signal perception, a less developed system of gradation of the strength of stimulation and a lesser ability to transmit rapid changes in the signal.

Somatosensory signals

Tactile sensitivity

Tactile sensations of touch, pressure and vibration are separate types of sensations, but are perceived by the same receptors.

· Feeling touch- the result of stimulation of sensitive nerve endings of the skin and underlying tissues.

· Feeling pressure occurs as a result of deformation of deep tissues.

· Vibration feeling occurs as a result of rapid, repeated sensory stimuli applied to the same receptors as those that sense touch and pressure.

Tactile receptors

Proprioceptive feeling

For material in this section, see the book.

Transmission routes somatosensory signals

Almost all sensory information from the body segments (see Fig. 9–8) enters the spinal cord through the central processes of the sensory neurons of the spinal ganglia passing through the dorsal roots (Fig. 9–2, 9–3). Having entered the spinal cord, the central processes of sensory neurons either go directly to the medulla oblongata (lemniscal system: thin or delicate fasciculus of Gaulle and cuneate fasciculus of Burdach), or end on interneurons, the axons of which go to the thalamus as part of the ventral, or anterior and lateral , or lateral spinothalamic ascending tract.

Rice . 9 – 2. Spinal cord . View from the back. Explanations in the text. For maps of the nuclei, laminae, and tracts of the spinal cord, see "Nuclei and Tracts of the Spinal Cord" in Chapter 13.

· Thin And wedge-shaped bunches - conductive ways proprioceptive And tactile sensitivity- pass as part of the posterior cord of the same side of the spinal cord and end in the thin and sphenoid nuclei of the medulla oblongata. The axons of the neurons of these nuclei along the medial loop (hence the name - lemniscal system) move to the opposite side and go to the thalamus.

· Spinothalamic path ventral- projection afferent pathway passing in the anterior cord of the opposite side. Peripheral processes of the first neurons located in the spinal ganglia carry out tactile And pressor Feel from mechanoreceptors skin. The central processes of these neurons enter through the dorsal roots into the dorsal funiculi, where they ascend 2–15 segments and form synapses with interneurons of the dorsal horns. The axons of these neurons move to the opposite side and pass further in the anterior peripheral zone of the anterolateral funiculi. From here, the fibers of the pathway ascend to the posterolateral ventral nucleus of the thalamus along with the lateral spinothalamic tract.

· Spinothalamic path lateral- projection afferent pathway passing in the lateral cord. Peripheral receptors are free nerve endings of the skin. The central processes of pseudounipolar neurons of the spinal ganglia enter the opposite part of the spinal cord through the lateral sections of the dorsal roots and, having risen 1–2 segments in the spinal cord, form synapses with neurons Roland's gelatinous substances. The axons of these neurons actually form the lateral spinothalamic tract. They go to the opposite side and rise in the lateral sections of the lateral cords. The spinothalamic tracts pass through the brainstem and terminate in the ventrolateral nuclei of the thalamus. This main path carrying out painful And temperature sensitivity.

Rice . 9 – 3. Ascending Paths sensitivity. A . The path from the sensory neurons of the spinal ganglia (the first, or primary sensory neuron) through the second neurons (interneurons of the spinal cord or nerve cells of the sphenoid and thin nucleus of the medulla oblongata) to the third neurons of the path - thalamic. The axons of these neurons project to the cerebral cortex. B . The location of neurons transmitting different modalities in the laminae (Roman numerals) of the spinal cord.

The posterior cord consists of thick myelinated nerve fibers that conduct signals at speeds from 30 to 110 m/s; spinothalamic tracts consist of thin myelinated fibers that conduct AP at speeds ranging from a few meters to 40 m/s.

Somatosensory bark

For material in this section, see the book.

Signal Processing in Ascending Projection Paths

For material in this section, see the book.

Painful sensitivity

Pain is an unpleasant sensory and emotional sensation associated with actual or potential tissue damage or described in terms of such damage. Pain is a protective signaling mechanism for the body and can occur in any tissue where signs of damage have appeared. Pain is divided into fast and slow, acute and chronic.

· Fast pain felt 0.1 seconds after the application of a painful stimulus. Rapid pain is described under many names: cutting, stabbing, sharp, electric, etc. From pain receptors to the spinal cord, pain signals are transmitted along small diameter fibers A d at speeds from 6 to 30 m/s.

· Slow pain occurs over 1 second or more and then slowly increases over many seconds or minutes (for example, slow burning, dull, throbbing, bursting, chronic pain). Slow chronic pain is transmitted along C fibers at a speed of 0.5 to 2 m/s.

The existence of a dual system for transmitting pain signals leads to the fact that strong sharp irritation often causes a double pain sensation. Fast pain is transmitted immediately, and a second or a little later slow pain is transmitted.

Reception of pain

Pain is caused by many factors: mechanical, thermal and chemical pain stimuli. Fast pain is generated mainly by mechanical and temperature stimuli, slow pain is generated by all types of stimuli. Some substances are known as chemical pain stimulants: potassium ions, lactic acid, proteolytic enzymes. Prostaglandins increase the sensitivity of pain endings, but do not directly excite them. Pain receptors ( nociceptors) are free nerve endings (see Fig. 8–1A). They are widely distributed in the superficial layers of the skin, periosteum, joints, and arterial walls. Other deep tissues have fewer free nerve endings, but extensive tissue damage can cause pain in almost all areas of the body. Pain receptors practically do not adapt.

· Action chemical incentives, causing pain, manifests itself when an extract from damaged tissue is injected into a normal area of ​​​​the skin. The extract contains all the chemical factors described above that cause pain. The most severe pain is caused by , which made it possible to consider it the main cause of pain when tissue is damaged. In addition, the intensity of pain correlates with a local increase in potassium ions and an increase in the activity of proteolytic enzymes. The appearance of pain in this case is explained by the direct influence of proteolytic enzymes on nerve endings and an increase in membrane permeability for K + , which is the direct cause of pain.

· Fabric ischemia, which occurs when blood circulation in the tissue stops, causes severe pain after a few minutes. It has been noticed that the higher the metabolism in the tissue, the faster the pain appears when blood flow is disrupted. For example, placing a cuff on the upper limb and pumping air until the blood flow completely stops causes pain to appear in the working muscle after 15–20 seconds. Under the same conditions, pain in the non-working muscle occurs a few minutes later.

· Dairy acid. A possible cause of pain during ischemia is the accumulation of large amounts of lactic acid, but it is no less likely that other chemical factors (for example, proteolytic enzymes) are formed in the tissue, and it is the latter that stimulate pain nerve endings.

· Muscular spasm leads to pain, which underlies many clinical pain syndromes. The cause of pain may be the direct effect of spasm on the mechanosensitive pain receptors of the muscles. It is more likely that the cause of pain is the indirect effect of muscle spasm, which compresses the blood vessels and causes ischemia. Finally, spasm increases the rate of metabolic processes in muscle tissue, creating conditions for increasing the effect of ischemia and the release of substances that induce pain.

· Painful receptors practically Not adapt. In some cases, the excitation of pain receptors not only does not decrease, but also continues to progressively increase (for example, in the form of a dull arching pain). Increased sensitivity of pain receptors is called hyperalgesia. A decrease in the threshold of pain sensitivity is detected with prolonged temperature stimulation. The lack of adaptive capacity in nociceptors does not allow the subject to forget about the harmful effects of painful stimuli on the tissues of his body.

Transmission of pain signals

Fast and slow pain correspond to their own nerve pathways: path carrying out fast pain And path carrying out slow chronic pain.

Carrying out quick pain

The conduction of rapid pain (Fig. 9–7A) from receptors is carried out by fibers of the Ad type, entering the spinal cord along the dorsal roots and synaptically contacting the neurons of the dorsal horn of the same side. After the formation of synapses with second-order neurons on the same side, the nerve fibers move to the opposite side and rise up to the brain stem as part of the spinothalamic tract in the anterolateral cords. In the brain stem, some fibers synaptically contact the neurons of the reticular formation, while the bulk of the fibers pass to the thalamus, ending in the ventro-basal complex along with the fibers of the lemniscal system, which carry tactile sensitivity. A small part of the fibers ends in the posterior nuclei of the thalamus. From these thalamic areas, signals are transmitted to other basal brain structures and to the somatosensory cortex (Figure 9-7A).

Rice . 9 – 7. Pathways of pain transmission sensitivity(A) and antinociceptive system (B).

· Localization fast pain in various parts of the body more distinct than slow chronic pain.

· Broadcast painful impulses(Fig. 9–7B, 9–8). Glutamate is involved in the transmission of pain stimuli as an excitatory neurotransmitter in the synapses between the central processes of sensory neurons of the spinal ganglion and the perikaryons of neurons of the spinothalamic tract. Blocking the secretion of substance P and relieving pain are realized through opioid peptide receptors built into the membrane of the terminal of the central process of a sensory neuron (an example of the phenomenon of presynaptic inhibition). The source of the opioid peptide is the interneuron.

Rice . 9–8. Pathway for pain impulses (arrows). Substance P transmits excitation from the central process of the sensory neuron to the neuron of the spinothalamic tract. Through opioid receptors, enkephalin from the interneuron inhibits the secretion of substance P from the sensory neuron and the transmission of pain signals.[ 11 ].

Carrying out slow chronic pain

The central processes of sensory neurons end on neurons of laminae II and III. The long axons of the second neurons pass to the other side of the spinal cord and, as part of the anterolateral cord, ascend into the brain. These fibers, which carry signals of slow chronic pain as part of the paleospinothalamic tract, have extensive synaptic connections in the brain stem, ending in the reticular nuclei of the medulla oblongata, pons and midbrain, in the thalamus, in the tegmental area and in the gray matter surrounding the aqueduct of Sylvius. From the brain stem, pain signals arrive to the intraplate and ventrolateral nuclei of the thalamus, the hypothalamus and other structures at the base of the brain (Fig. 9-7B).

· Localization slow chronic pain. Slow chronic pain is not localized in individual points of the body, but in large parts of it, such as the arm, leg, back, etc. This is explained by polysynaptic, diffuse connections of the pathways conducting slow pain.

· Central grade slow pain. Complete removal of the somatosensory cortex in animals does not impair their ability to sense pain. Therefore, pain impulses entering the brain through the reticular formation of the brainstem, the thalamus and other underlying centers can cause conscious perception of pain. The somatosensory cortex is involved in assessing the quality of pain.

· Neurotransmitter slow pain at the endings of C‑fibers - . Type C pain fibers entering the spinal cord release the neurotransmitters glutamate and substance P at their endings. Glutamate acts within a few milliseconds. Substance P is released more slowly, reaching its effective concentration within seconds or even minutes.

Pain suppression system

The human body not only senses and determines the strength and quality of pain signals, but is also able to reduce and even suppress the activity of pain systems. The range of individual responses to pain is unusually wide, and the response to pain largely depends on the brain’s ability to suppress pain signals entering the nervous system using the antinociceptive (analgesic, anti-pain) system. The antinociceptive system (Fig. 9–7B) consists of three main components.

1 . Complex braking pain, located in the posterior horns of the spinal cord. Here pain is blocked before it reaches the receptive parts of the brain.

2 . Big core seam, located in the midline between the pons and the medulla oblongata; reticular paragiant cell core, located in the lateral part of the medulla oblongata. From these nuclei, signals travel along the posterolateral columns to the spinal cord.

3 . Okolovoprovodnoe gray substance And periventricular region the midbrain and upper pons, surrounding the aqueduct of Sylvius and parts of the third and fourth ventricles. Neurons from these analgesic areas send signals to the raphe nucleus magnus and the reticular paragiant cell nucleus.

Electrical stimulation of the periaqueductal gray matter or raphe nuclei magnus almost completely suppresses pain signals passing through the dorsal roots of the spinal cord. In turn, stimulation of overlying brain structures excites the periventricular nuclei and the forebrain medial fascicle of the hypothalamus and thereby causes an analgesic effect.

· Neurotransmitters antinociceptive systems. The mediators released at the endings of the nerve fibers of the analgesic system are and. Various parts of the analgesic system are sensitive to morphine, opiates and opioids ( b -endorphin, enkephalin, dynorphin). In particular, enkephalins and dynorphin were found in the structures of the analgesic system of the brain stem and spinal cord.

Nerve fibers containing synapses form synapses with the neurons of the raphe nuclei. The axons of these neurons terminate in the dorsal horn of the spinal cord and discharge from their endings. Serotonin, in turn, excites enkephalinergic neurons in the dorsal horn of the spinal cord (Fig. 9–8). Enkephalin causes presynaptic inhibition and postsynaptic inhibition at type C and A pain fiber synapses d in the dorsal horns of the spinal cord. It is assumed that presynaptic inhibition occurs as a result of blockade of calcium channels in the membrane of nerve endings.

Central braking And distracting irritation

· From the standpoint of activation of the analgesic system, the well-known fact of forgetting pain by the wounded during battle (stress analgesia), and the reduction of pain when stroking or vibrating a damaged area of ​​the body, known to many from personal experience, is explained.

· Stimulating the painful area with an electric vibrator also provides some pain relief. Acupuncture has been used for over 4,000 years to prevent or relieve pain, and in some cases, acupuncture is used to perform major surgical procedures.

· The inhibition of pain signals in the central sensory pathways can also explain the effectiveness of distracting stimulation used to stimulate the skin in the area of ​​inflammation of the internal organ. So, mustard plasters and pepper plasters work on this principle.

Referred pain

Irritation of the internal organs often causes pain, which is felt not only in the internal organs, but also in some somatic structures located quite far from the place where the pain is caused. This kind of pain is called referred (radiating).

The best known example of referred pain is cardiac pain that radiates to the left arm. However, the future doctor should know that areas of pain reflection are not stereotypical, and unusual areas of reflection are observed quite often. Heart pain, for example, can be purely abdominal, it can radiate to the right arm and even to the neck.

Rule dermatomers . Afferent fibers from the skin, muscles, joints and internal organs enter the spinal cord along the dorsal roots in a certain spatial order. Cutaneous afferent fibers from each dorsal root innervate a limited area of ​​skin called the dermatomere (Figure 9-9). Referred pain usually occurs in structures developing from the same embryonic segment, or dermatomere. This principle is called the “dermatomer rule.” For example, the heart and left arm have the same segmental nature, and the testicle migrated with its nerve supply from the urogenital ridge, from which the kidneys and ureters arose. Therefore, it is not surprising that pain that originates in the ureters or kidneys radiates to the testicle.

Rice . 9 – 9. Dermatomers

Convergence and relief in the mechanism of referred pain

Not only the visceral and somatic nerves that enter the nervous system at one segmental level, but also a large number of sensory nerve fibers passing through the spinothalamic tracts take part in the development of referred pain. This creates conditions for the convergence of peripheral afferent fibers on thalamic neurons, i.e. somatic and visceral afferents converge on the same neurons (Fig. 9–10).

· Theory convergence. Greater speed, consistency and frequency of information about somatic pain helps the brain to consolidate information that signals entering the corresponding nerve pathways are caused by painful stimuli in certain somatic areas of the body. When the same nerve pathways are excited by the activity of visceral pain afferent fibers, the signal reaching the brain is not differentiated, and pain is projected to the somatic area of ​​the body.

· Theory relief. Another theory of the origin of referred pain (the so-called relief theory) is based on the assumption that impulses from internal organs lower the threshold of spinothalamic neurons to the effects of afferent pain signals from somatic areas. Under conditions of relief, even minimal pain activity from the somatic area passes to the brain.

Rice . 9 – 10. Referred pain

If convergence is the only explanation for the origin of referred pain, then local anesthesia of the area of ​​referred pain should have no effect on the pain. On the other hand, if subthreshold relieving influences are involved in the occurrence of referred pain, then the pain should disappear. The effect of local anesthesia on the area of ​​referred pain varies. Severe pain usually does not go away, moderate pain may stop completely. Therefore, both factors are convergence And relief- participate in the occurrence of referred pain.

Unusual and long lasting pain

In some people, damage and disease processes affecting the peripheral nerves cause severe, debilitating, and abnormally persistent pain.

· Hyperalgesia, in which stimuli that normally lead to a moderate feeling of pain cause severe, long-lasting pain.

· Causalgia- a persistent burning sensation, usually developing after vascular damage to the sensory fibers of the peripheral nerve.

· Allodynia- painful sensations in which neutral stimuli (for example, a slight breath of wind or the touch of clothing cause intense pain).

· Hyperpathy- a painful sensation in which the pain threshold is increased, but when it is reached, intense, burning pain flares up.

· Phantom pain is a painful sensation in a missing limb.

The causes of these pain syndromes are not fully established, but it is known that these types of pain are not relieved by local anesthesia or nerve cutting. Experimental studies indicate that nerve damage leads to intensive proliferation and branching of noradrenergic nerve fibers in the sensory ganglia, from where the dorsal roots emerge towards the damaged area. Apparently, sympathetic discharges contribute to the appearance of unusual pain signals. Thus, a vicious circle arises on the periphery. The damaged nerve fibers related to it are stimulated by norepinephrine at the level of the dorsal roots. a -Adrenergic blockade reduces painful causalgic sensations.

Thalamic syndrome. Spontaneous pain may occur at the level of the thalamus. In thalamic syndrome, there is damage to the posterior thalamic nuclei, usually caused by obstruction of the branches of the posterior cerebral artery. Patients with this syndrome experience bouts of prolonged, severe, extremely unpleasant pain that occur spontaneously or in response to various sensory stimuli.

Pain can be relieved by using adequate doses of analgesics, but this does not happen in all cases. To alleviate unbearable pain, the method of chronic irritation of the dorsal roots with implanted electrodes is used. The electrodes are connected to a portable stimulator, and the patient can stimulate himself if necessary. Relief from pain is achieved, apparently, by antidromic conduction of impulses through collaterals to the antipain system of the dorsal roots. Self-stimulation of the periaqueductal gray matter also helps reduce unbearable pain, probably due to the release.

Visceral pain

In practical medicine, pain that occurs in internal organs is an important symptom of inflammation, infectious diseases and other disorders. Any stimulus that overstimulates nerve endings in the internal organs causes pain. These include ischemia of visceral tissue, chemical damage to the surface of internal organs, spasm of the smooth muscles of hollow organs, stretching of hollow organs and stretching of the ligamentous apparatus. All types of visceral pain are transmitted through pain nerve fibers passing through the autonomic nerves, mainly sympathetic. Pain fibers are represented by thin C-fibers that conduct chronic pain.

Causes of visceral pain

· Ischemia causes pain as a result of the formation of acidic metabolic products and tissue breakdown products, as well as proteolytic enzymes that irritate pain nerve endings.

· Spasm hollow organs(such as a section of the intestine, ureter, gallbladder, bile ducts, etc.) causes mechanical irritation of pain receptors. Sometimes mechanical irritation is combined with ischemia caused by spasm. Often pain sensations from a spasmodic organ take the form of an acute spasmodic attack, increasing to a certain extent, and then gradually decreasing.

· Chemical irritation may occur in cases where damaging substances enter the abdominal cavity from the gastrointestinal tract. The entry of gastric juice into the abdominal cavity covers a wide area of ​​irritation of pain receptors and generates unbearably acute pain.

· Overextension hollow organs mechanically irritates pain receptors and disrupts blood flow in the wall of the organ.

Headache

Headache is a type of referred pain, perceived as a painful sensation that occurs on the surface of the head. Many types of pain arise from painful stimuli inside the skull, others from stimuli located outside the skull.

Headache intracranial origin

· Sensitive To pain region inside skulls. The brain itself is completely devoid of pain sensitivity. Even an incision or electrical stimulation of the sensory cortex can only accidentally cause pain. Instead of pain in the areas represented in the somatosensory cortex, a slight tingling sensation occurs - paresthesia. Therefore, it is unlikely that most headaches are caused by damage to the brain parenchyma.

· Pressure on venous sinuses surrounding the brain, damage to the tentorium or stretching of the dura mater at the base of the brain can cause intense pain, defined as a headache. All types of trauma (crushing, stretching, twisting of the vessels of the meninges) cause headaches. The structures of the middle cerebral artery are especially sensitive.

· Meningeal pain- the most severe type of headaches that occur during inflammatory processes of the meninges and are reflected over the entire surface of the head.

· Pain at decrease pressure in the cerebrospinal fluid occur due to a decrease in the amount of fluid and stretching of the meninges by the weight of the brain itself.

· Pain at migraine occurs as a result of spastic vascular reactions. It is believed that migraine occurs as a result of prolonged emotions or stress that cause spasm of certain arterial vessels of the head, including those supplying the brain. As a result of ischemia caused by spasm, loss of tone of the vascular wall occurs, lasting from 24 to 48 hours. Pulse fluctuations in blood pressure more intensely stretch the relaxed atonic vascular walls of the arteries, and this overstretching of the arterial walls, including extracranial ones (for example, the temporal arteries) leads to an attack of headache.

The origin of migraine is also explained by emotional abnormalities leading to spreading cortical depression. Depression causes a local accumulation of potassium ions in the brain tissue, initiating vascular spasm.

· Alcoholic pain caused by the direct toxic irritant effect of acetaldehyde on the meninges.

Headaches of extracranial origin

· Head ones pain V result muscular spasm occur when there is emotional tension in many muscles attached to the skull and shoulder girdle. The pain is reflected across the surface of the head and resembles intracranial pain.

· Head ones pain at irritation nasal cavities And subordinate clauses sinuses nose do not have great intensity and are reflected on the frontal surface of the head.

· Head ones pain at violations functions eye can occur with strong contractions of the ciliary muscle, when trying to achieve better vision. This can cause a reflex spasm of the facial and outer eye muscles and headaches. The second type of pain can be observed when the retina is “burned” by ultraviolet radiation, as well as when the conjunctiva is irritated.

Physiology of pain

In the narrow sense of the word, pain is an unpleasant sensation that occurs under the action of super-strong stimuli that cause structural and functional disorders in the body. The difference between pain and other sensations is that it does not inform the brain about the quality of the stimulus, but indicates that the stimulus is damaging. Another feature of the pain sensory system is its most complex and powerful efferent control.

The pain analyzer launches several programs in the central nervous system for the body's response to pain. Therefore, pain has several components. The sensory component of pain characterizes it as an unpleasant, painful sensation; affective component – ​​as a strong negative emotion; motivational component – ​​as a negative biological need that triggers the body’s behavior aimed at recovery. The motor component of pain is represented by various motor reactions: from unconditioned flexion reflexes to motor programs of anti-pain behavior. The vegetative component characterizes dysfunction of internal organs and metabolism in chronic pain. The cognitive component is associated with self-assessment of pain, in which pain acts as suffering. When other systems operate, these components are weakly expressed.

The biological role of pain is determined by several factors. Pain acts as a signal about threat or damage to body tissues and warns them. Pain has a cognitive function: through pain, a person learns to avoid possible dangers of the external environment. The emotional component of pain performs the function of reinforcement in the formation of conditioned reflexes. Pain is a factor in mobilizing the body’s protective and adaptive reactions when its tissues and organs are damaged.

There are two types of pain – somatic and visceral. Somatic pain is divided into superficial and deep. Superficial pain can be early (fast, epicric) and late (slow, protopathic).

There are three theories of pain.

1. The intensity theory was proposed by E. Darwin and A. Goldsteiner. According to this theory, pain is not a specific feeling and does not have its own special receptors. It occurs when super-strong stimuli act on the receptors of the five known sense organs. Convergence and summation of impulses in the spinal cord and brain are involved in the formation of pain.

2. The theory of specificity was formulated by the German physiologist M. Frey. According to this theory, pain is a specific feeling that has its own receptor apparatus, afferent fibers and brain structures that process pain information. This theory later received more complete experimental and clinical confirmation.

3. The modern theory of pain is based primarily on the theory of specificity. The existence of specific pain receptors has been proven. At the same time, the modern theory of pain uses the position about the role of central summation and convergence in the mechanisms of pain. The largest achievements of the modern theory of pain are the development of mechanisms for the central perception of pain and the triggering of the body's anti-pain system.

Pain receptors

Pain receptors are the free endings of sensitive myelinated nerve fibers Aδ and non-myelinated C fibers. They are found in the skin, mucous membranes, periosteum, teeth, muscles, joints, internal organs and their membranes, and blood vessels. They are not found in the nervous tissue of the brain and spinal cord. Their greatest density is found at the border of dentin and tooth enamel.

The following main types of pain receptors are distinguished:

1. Mechanonociceptors and mechanothermal nociceptors of Aδ-fibers react to strong mechanical and thermal stimuli, conduct rapid mechanical and thermal pain, quickly adapt; located mainly in the skin, muscles, joints, periosteum; their afferent neurons have small receptive fields.

2. Polysensory nociceptors of C-fibers respond to mechanical, thermal and chemical stimuli, conduct late, poorly localized pain, and adapt slowly; their afferent neurons have large receptive fields.

Pain receptors are stimulated by three types of stimuli:

1. Mechanical irritants that create a pressure of more than 40 g/mm 2 when squeezing, stretching, bending, twisting.

2. Thermal irritants can be thermal (> 45 0 C) and cold (< 15 0 С).

3. Chemical irritants released from damaged tissue cells, mast cells, platelets (K +, H +, serotonin, acetylcholine, histamine), blood plasma (bradykinin, kallidin) and the endings of nociceptive neurons (substance P). Some of them excite nociceptors (K +, serotonin, histamine, bradykinin, ADP), others sensitize them.

Properties of pain receptors: pain receptors have a high threshold of excitation, which ensures their response only to extreme stimuli. Nociceptors of C-afferents adapt poorly to long-acting stimuli. It is possible to increase the sensitivity of pain receptors - a decrease in the threshold of their irritation with repeated or prolonged stimulation, which is called hyperalgesia. In this case, nociceptors are capable of responding to stimuli of subthreshold magnitude, as well as being excited by stimuli of other modalities.

Pathways of pain sensitivity

Neurons that perceive pain impulses. From the pain receptors of the trunk, neck and limbs, Aδ- and C-fibers of the first sensory neurons (their bodies are located in the spinal ganglia) go as part of the spinal nerves and enter through the dorsal roots into the spinal cord, where they branch in the dorsal columns and form synaptic connections directly or through interneurons with second sensory neurons, the long axons of which are part of the spinothalamic tracts. At the same time, they excite two types of neurons: some neurons are activated only by painful stimuli, others - convergent neurons - are also excited by non-painful stimuli. The second neurons of pain sensitivity are predominantly part of the lateral spinothalamic tracts, which conduct most of the pain impulses. At the level of the spinal cord, the axons of these neurons move to the side opposite to the stimulation; in the brain stem they reach the thalamus and form synapses on the neurons of its nuclei. Part of the pain impulses of the first afferent neurons are switched through interneurons to motor neurons of the flexor muscles and participate in the formation of protective pain reflexes. In the lateral spinothalamic tract, the evolutionarily younger neospinothalamic tract and the ancient paleospinothalamic tract are distinguished.

The neospinothalamic pathway conducts pain signals along Aδ fibers mainly to specific sensory (ventral posterior) nuclei of the thalamus, which have a good topographic projection to the periphery of the body. In addition, a small part of the impulses enters the reticular formation of the trunk and then to the nonspecific nuclei of the thalamus. The transmission of excitation at the synapses of this pathway is carried out using the fast-acting transmitter glutamate. From specific nuclei of the thalamus, pain signals are transmitted predominantly to the sensory cortex of the cerebral hemispheres. These features form the main function of the neospinothalamic pathway - conducting “fast” pain and perceiving it with a high degree of localization.

The paleospinothalamic pathway conducts pain signals along C-fibers mainly to the nonspecific nuclei of the thalamus directly or after switching in the neurons of the reticular formation of the brainstem. The transmission of excitation at synapses in this pathway occurs more slowly. The mediator is substance P. From nonspecific nuclei, impulses enter the sensory and other parts of the cerebral cortex. A small part of the impulse also enters specific nuclei of the thalamus. Basically, the fibers of this pathway end on neurons of 1) nonspecific nuclei of the thalamus; 2) reticular formation; 3) central gray matter; 4) blue spot; 5) hypothalamus. “Late”, poorly localized pain is transmitted through the paleospinothalamic pathway, and affective and motivational manifestations of pain sensitivity are formed.

In addition, pain sensitivity is partially carried out through other ascending pathways: the anterior spinothalamic, thin and cuneate pathways.

The above pathways also conduct other types of sensitivity: temperature and tactile.

The role of the cerebral cortex in pain perception

Full sensory perception of pain by the body without the participation of the cerebral cortex is impossible.

The primary projection field of the pain analyzer is located in the somatosensory cortex of the posterior central gyrus. It provides the perception of “quick” pain and identification of its location on the body. To more accurately identify the location of pain, the process necessarily includes neurons of the motor cortex of the anterior central gyrus.

The secondary projection field is located in the somatosensory cortex at the border of the intersection of the central sulcus with the superior edge of the temporal lobe. The neurons of this field have bilateral connections with the nuclei of the thalamus, which allows this field to selectively filter painful excitations passing through the thalamus. And this, in turn, allows this field to be involved in processes associated with retrieving the engram of the necessary behavioral act from memory, its implementation in the activities of effectors and assessing the quality of the achieved useful result. The motor components of pain behavior are formed in the joint activity of the motor and premotor cortex, basal ganglia and cerebellum.

The frontal cortex plays an important role in pain perception. It provides self-assessment of pain (its cognitive component) and the formation of targeted pain behavior.

The limbic system (cingulate gyrus, hippocampus, dentate gyrus, amygdala complex of the temporal lobe) receives pain information from the anterior nuclei of the thalamus and forms the emotional component of pain, triggers autonomic, somatic and behavioral reactions that provide adaptive reactions to the painful stimulus.

Some types of pain

There are pains that are named projection or phantom. Their occurrence is based on the law of pain projection: no matter what part of the afferent pathway is irritated, pain is felt in the area of ​​the receptors of this sensory pathway. According to modern data, all parts of the pain sensory system are involved in the formation of this type of pain.

There are also so-called reflected pain: when pain is felt not only in the affected organ, but also in the corresponding dermatome of the body. The areas of the body surface of the corresponding dermatome where the sensation of pain occurs are called Zakharyin–Ged zones. The occurrence of referred pain is due to the fact that the neurons carrying pain impulses from the receptors of the affected organ and the skin of the corresponding dermatome converge on the same neuron of the spinothalamic tract. Irritation of this neuron from the receptors of the affected organ in accordance with the law of pain projection leads to the fact that pain is also felt in the area of ​​skin receptors.

Antinociceptive system

The anti-pain system consists of four levels: spinal, brainstem, hypothalamic and cortical.

1. Spinal level of the antinociceptive system. Its important component is the “gate control” of the spinal cord, the concept of which has the following basic principles: the transmission of pain nerve impulses from the first neurons to the neurons of the spinothalamic tract (second neurons) in the posterior columns of the spinal cord is modulated by the spinal gate mechanism - inhibitory neurons located in the gelatinous substance spinal cord. The branching axons of various sensory pathways end on these neurons. In turn, neurons of the gelatinous substance exert presynaptic inhibition at the sites of switching of the first and second neurons of pain and other sensory pathways. Some neurons are convergent: neurons form synapses on them not only from pain receptors, but also from other receptors. Spinal portal control is regulated by the ratio of impulses arriving along afferent fibers of large diameter (non-pain sensitivity) and small diameter (pain sensitivity). The intense flow of impulses along large-diameter fibers limits the transmission of pain signals to the neurons of the spinothalamic pathways (closes the “gate”). On the contrary, an intense flow of pain impulses along the first afferent neuron, inhibiting inhibitory interneurons, facilitates the transmission of pain signals to the neurons of the spinothalamic pathways (opens the “gate”). The spinal gate mechanism is under the constant influence of nerve impulses from brain stem structures, which are transmitted along descending pathways to both neurons of the substantia gelatinosa and neurons of the spinothalamic tract.

2. Brainstem level of the antinociceptive system. The stem structures of the analgesic system include, firstly, the central gray matter and raphe nuclei, forming a single functional block, and secondly, the magnocellular and paragiant cell nuclei of the reticular formation and the locus coeruleus. First complex blocks the passage of pain impulses at the level of relay neurons of the nuclei of the dorsal horns of the spinal cord, as well as relay neurons of the sensory nuclei of the trigeminal nerve, forming the ascending pathways of pain sensitivity. The second complex excites almost the entire antinociceptive system (see Fig. 1).

3. The hypothalamic level of the antinociceptive system, on the one hand, functions independently, and on the other, acts as a setting that controls and regulates antinociceptive mechanisms at the stem level due to connections between hypothalamic neurons of different nuclear affiliations and different neurochemical specificities. Among them, neurons were identified, in the endings of which enkephalins, β-endorphin, norepinephrine, and dopamine are released (see Fig. 2).

4. Cortical level of the antinociceptive system. The somatosensory area of ​​the cerebral cortex unites and controls the activity of antinociceptive structures at various levels. In this case, the most important role in activation spinal and stem structures plays the secondary sensory area. Its neurons form the largest number of fibers of descending control of pain sensitivity, heading to the dorsal horns of the spinal cord and the nuclei of the brain stem. The secondary sensory cortex modifies the activity of the stem complex of the antinociceptive system. In addition, the somatosensory fields of the cerebral cortex control the conduction of afferent pain impulses through the thalamus. In addition to the thalamus, the cerebral cortex regulates the passage of pain impulses in the hypothalamus, limbic system, reticular formation, and spinal cord. The leading role in providing cortico-hypothalamic influences is assigned to neurons of the frontal cortex.

Mediators of the antinociceptive system

Mediators of the analgesic system include peptides that are formed in the brain, adenohypophysis, adrenal medulla, gastrointestinal tract, placenta from inactive precursors. Now opiate mediators of the antinociceptive system include: 1) ά-, β-, γ-endorphins; 2) enkephalins; 3) dynorphins. These mediators act on three types of opiate receptors: μ-, δ-, κ-receptors. The most selective stimulator of μ-receptors are endorphins, δ-receptors are enkephalins, and κ-receptors are dynorphins. The density of μ- and κ-receptors is high in the cerebral cortex and spinal cord, and average in the brain stem; the density of δ-receptors is average in the cerebral cortex and spinal cord, low in the brain stem. Opioid peptides inhibit the action of substances that cause pain at the level of nociceptors, reduce the excitability and conductivity of pain impulses, and inhibit the evoked reaction of neurons located in the circuits that transmit pain impulses. These peptides reach the neurons of the pain sensory system with blood and cerebrospinal fluid. Opioid mediators are released in the synaptic endings of neurons of the analgesic system. The analgesic effect of endorphins is high in the brain and spinal cord, the effect of enkephalins in these structures is medium, the effect of dynorphins in the brain is low, and in the spinal cord it is high.

Fig.1. Interaction of the main elements of the first level analgesic system: brain stem - spinal cord. (open circles are excitatory neurons, black circles are inhibitory).

Fig.2. The mechanism of operation of the body's second-level pain-relieving system (hypothalamus - thalamus - brain stem) using opioids.

Light circles are excitatory neurons, black circles are inhibitory.

The severity of pain is not determined by the strength of exogenous or endogenous pain alone. It largely depends on the ratio of the activities of the nociceptive and antinociceptive parts of the pain system, which has adaptive significance.

Pain receptors (nociceptors) respond to stimuli that threaten the body with damage. There are two main types of nociceptors: Adelta mechanonociceptors and polymodal C nociceptors (there are several other types). As their name suggests, mechanonociceptors are innervated by thin myelinated fibers, and polymodal C-nociceptors are innervated by unmyelinated C-fibers. Delta-mechanonociceptors respond to strong mechanical irritation of the skin, for example, a needle prick or a pinch with tweezers. They generally do not respond to thermal and chemical painful stimuli unless they have been previously sensitized. In contrast, multimodal C-nociceptors respond to pain stimuli of various types: mechanical, temperature (Fig. 34.4) and chemical.

For many years, it was unclear whether pain results from the activation of specific fibers or from overactivity of sensory fibers that normally have other modalities. The latter possibility seems to be more consistent with our ordinary experience. With the possible exception of smell, any sensory stimulus of excessive intensity—blinding light, ear-piercing sound, heavy blow, heat or cold outside the normal range—results in pain. This common sense view was stated by Erasmus Darwin in the late 18th century and William James in the late 19th century. Common sense, however, here (as elsewhere) leaves something to be desired. Currently, there is little doubt that in most cases the sensation of pain arises as a result of stimulation of specialized nociceptive fibers. Nociceptive fibers do not have specialized endings. They are present in the form of free nerve endings in the dermis of the skin and in other places in the body. Histologically, they are indistinguishable from C-mechanoreceptors (MECHANSENSITIVITY) and - and A-delta thermoreceptors (chapter THERMAL SENSITIVITY). They differ from the mentioned receptors in that the threshold for their adequate stimuli is higher than the normal range. They can be divided into several different types based on the criterion of which sensory modality provides an adequate stimulus for them. Noxious thermal and mechanical stimuli are detected by small diameter myelinated fibers, Table 2.2 shows that these are classified as category A delta fibers. Polymodal fibers, which respond to a wide variety of stimulus intensities of different modalities, are also small in diameter but are not myelinated. Table 2.2 shows that these fibers are class C. A delta fibers conduct impulses with a frequency of 5-30 m/s and are responsible for “fast” pain, a sharp stabbing sensation; C-fibers conduct more slowly - 0.5 - 2 m/s and signal “slow” pain, often prolonged and often turning into dull pain. AMT (Mechano-thermo-nociceptors with A delta fibers) are divided into two types. AMT type 1 is mainly found in non-hairy skin. Type 2 AMTs are found mainly in hairy skin. Finally, C-fiber nociceptors (CMT fibers) have a threshold in the range of 38°C - 50°C and respond with a constant activity that depends on the intensity of the stimulus (Fig. 21.1a). AMT and CMT receptors, as their names indicate, respond to both thermal and mechanical stimuli. The physiological situation, however, is far from simple. The mechanism of transmission of these two modalities is different. Application of capsaicin does not affect sensitivity to mechanical stimuli, but inhibits the response to thermal ones. Moreover, while capsaicin has an analgesic effect on the thermal and chemical sensitivity of multimodal C-fibers in the cornea, it does not affect mechanosensitivity. Finally, it has been shown that mechanical stimuli that generate the same level of activity in the SMT fibers as thermal ones nevertheless cause less pain. Perhaps inevitably, the wider surface area covered by a thermal stimulus involves the activity of more CMT fibers than would be the case with a mechanical stimulus.

Sensitization of nociceptors (increased sensitivity of afferent receptor fibers) occurs after their response to a harmful stimulus. Sensitized nociceptors respond more intensely to a repeated stimulus because their threshold is lowered (Fig. 34.4). In this case, hyperalgesia is observed - more severe pain in response to a stimulus of the same intensity, as well as a decrease in the pain threshold. Sometimes nociceptors generate a background discharge that causes spontaneous pain.

Sensitization occurs when chemical factors such as K+ ions, bradykinin, serotonin, histamine, eicosanoids (prostaglandins and leukotrienes) are released near the nociceptive nerve endings as a result of tissue damage or inflammation. Let's say a harmful stimulus hits the skin and destroys the cells of the tissue area near the nociceptor (Fig. 34.5, a). K+ ions emerge from dying cells, which depolarize the nociceptor. In addition, proteolytic enzymes are released; when they interact with blood plasma globulins, bradykinin is formed. It binds to the receptor molecules of the nociceptor membrane and activates the second messenger system, which sensitizes the nerve ending. Other released chemicals, such as platelet serotonin, mast cell histamine, and eicosanoids of various cellular elements, contribute to sensitization by opening ion channels or activating second messenger systems. Many of them also affect blood vessels, immune system cells, platelets, and other effectors involved in inflammation.

In addition, activation of the nociceptor terminal can release regulatory peptides such as substance P (SP) and calcitonin gene-encoded peptide (CGRP) from other terminals of the same nociceptor via the axon reflex (Fig. 34.5b). A nerve impulse arising in one of the branches of the nociceptor is directed along the maternal axon to the center. At the same time, it spreads antidromically along the peripheral branches of the axon of the same nociceptor, resulting in the release of substance P and CGRP in the skin (Fig. 34.5, b). These peptides cause

Factors leading to activation of muscle pain receptors are also described: mechanical trauma, disruption of the integrity of blood vessels and muscle fibers, increased concentration of hydrogen ions.

Muscle pain receptors (nociceptors)

The concept of nociceptive pain

Pain is a special type of sensitivity associated with the action of a pathogenic stimulus and characterized by subjectively unpleasant sensations. Pain is also characterized by significant changes in the body, up to and including serious disruption of its vital functions and even death.

Nociceptive call pain caused by the influence of any factor (mechanical trauma, burn, inflammation, etc.) on peripheral pain receptors in the absence of damage to other parts of the nervous system.

Sensory nerves and receptors

Sensory fibers of type Aδ and C-fibers are responsible for pain sensitivity. These fibers are excited only by very strong painful stimulation. When they are blocked, pain sensitivity completely disappears. The endings of Aδ and C fibers are pain receptors. These fibers innervate the skin, deep tissues, internal organs and muscles.

Location of muscle pain receptors (nociceptors)

Painful nerve endings are distributed unevenly throughout the body. They cover the entire skin like a network. They are present in smaller quantities in muscles. Muscle pain receptors are located diffusely between muscle fibers, in the connective tissue sheaths surrounding the muscle fibers and the muscle as a whole and in the area of ​​the musculotendinous junction. They conduct pain impulses from the muscle along A δ -fibers and C-fibers to the cerebral cortex, where an increase in impulse activity from nociceptors is perceived as a feeling of pain.

Activation of muscle nociceptors

Muscle nociceptors are easily excited by intense damaging mechanical effects. Activation and increased sensitivity of pain receptors located between muscle fibers and in the tendon can be caused by a variety of pathophysiological conditions. The most well-known option is acute trauma.

Activation of muscle pain receptors can be caused not only mechanically, but also by a violation of the integrity of blood vessels and muscle fibers. As a result, there is an increase in the concentration of endogenous substances in the tissue, causing an increase in the sensitivity of nociceptors. Substances that cause pain include a high concentration of hydrogen ions (H +). It is known that when performing strength exercises aimed at hypertrophy of muscle fibers, lactate accumulates in them and the concentration of hydrogen ions increases. This is one of the reasons that causes pain in the muscles.

Literature

1. Alekseev V.V. Myogenic pain syndromes: pathogenesis and therapy // Effective pharmacotherapy, 2011.- T. 17. P. 30-34.
2. Boxer O.Ya., Grigoriev K.I. The science of pain: pathophysiological and medical-psychological aspects // Nurse, 2005.- 8.- P.2-5.