The mechanism of pain is complex. The final perception is the result of the interaction of nociceptive and antinociceptive systems. The emergence of pain begins with a specific pain receptors – nociceptors (from lat. – POS-damage). Nociceptors are the branching of afferent nerve endings located in different organs and tissues. In the skin and dentin of the teeth were found peculiar complex of nerves with cells of innervated tissues, which are considered as complex receptors in pain sensitivity. Nociceptors respond to both exogenous and endogenous stimuluses. Sometimes playing free card games helps a lot. Among the latest textile agents (histamine, serotonin, prostaglandins, potassium ions and hydrogen), plasma (bradykinin) and substance P, released from nerve endings. Substance P is a mediator of neuronal posterior horn of the spinal cord. Activate Nociceptors can and debris in the tissue inflammation and hypoxia. Endogenously formed algogennye (causing pain) substances play an important role in the occurrence of muscular and visceral pain. Sometimes steroids have a very strong impact on humans’ health.
Implementation pain sensitivity is on high speed conduct thin myelinated fibers of the A-B-and slow amyelinic C-fibers. These fibers (A-B and C), which are the main agents of cutaneous and visceral pain sensitivity, in the rear end horns of the spinal cord. There are two types of pain: a primary, fast, pinpoint, unpainted emotional pain (the specific path of pain) and secondary – the slow, diffuse, painful, dull ache with a distinctly emotional and autonomic manifestations (pupil dilation, increased sweating, increasing frequency heart rate and respiration) – a non-specific way of pain, many neuron.
The initial pain associated with rapid activation thin myelin AB-fibers, is perceived as pain signaling effect and is accompanied by a motor reaction.
Secondary pain is caused by afferent impulses in the slow amyelinic C-fibers and causes emotional and psychological experience of pain. Rear horn of the spinal cord, which receives a-b-and C-fibers, are the first central part of sensory information. Specific and nonspecific ways of pain sensitivity starting from the rear horn neurons of the spinal cord. The specific path includes: nucleus of the medulla oblongata, ventral nucleus of the thalamus, posterior central gyrus of the cerebral cortex. Nonspecific way – gelatinous substance of spinal cord, giant-cell nucleus bulbar division, the midbrain reticular formation, hypothalamus, nonspecific thalamic nuclei, limbic system, the upper frontal, parietal gyrus of the cerebral cortex. Posterior horn neurons can be divided into 3 groups. The first consists of cells activated by nociceptive stimuli A-b-and C-fibers. The second involves the cells responsible for nenotsitseptivnye impact. Third – represented by neurons gelatinous substance that modulates activation of the cells forming the first group and the ascending afferent pathways. Afferent tracts carry pain to the midbrain reticular formation, hypothalamus, nonspecific nuclei of the thalamus. limbic system and cerebral cortex, altering the emotional evaluation of pain, autonomic and hormonal responses to it. Excitation posterior horn of the spinal cord can be transmitted to the anterior horn motor neurons, which is manifested in motor acts (active defense reaction “avoidance”) or on neurons of the lateral horns (which are localized in preganglionic sympathetic neurons), resulting in activated sympathetic impulses (there is tachycardia, increased blood pressure).
A new approach to studying the formation of pain reaction and analgesia associated with the opening of analgesic (antinociceptive) zones of the brain, electrical stimulation that causes pain relief. Antinociceptive system is a central mechanism for the regulation of pain and changes in the organism’s reaction to it. In turn, the pain is nociceptive effects are the main factors that trigger and activate endogenous Analgesic system.
The membranes of neurons involved in the conduct pain impulses, there are specific “opiate” receptors. They are excited by endogenous neuropeptides – enkefalinami (therefore sometimes referred to as “enkefalinovye receptors), or endorphins, have a more complicated structure. Initiation of opioid receptors reduces the release of neurotransmitters – chemical agents that cause pain (serotonin, histamine, acetylcholine, prostacyclin, bradikardin, substance P, etc.). There are several types of receptors: m (mu), d (delta), k (kappa), s (sigma), e (epsilon), which have different functional significance. Proved that under the action of m-receptors observed analgesic effect, respiratory depression and physical dependence; k-receptor stimulation causes analgesia, calming effect, etc.
Narcotic analgesics because of their structural similarity with molecules of enkephalins and endorphins (the presence of tyrosine residues), interact with and stimulate opiate receptors, in addition, bind enkefalinazy – enzymes that break down enkephalins, increasing thus the level of these neurotransmitters.
The drug stimulates the activity of antinociceptive systems, enhancing the braking effect on the conduct of pain and its emotional expression.
Center antinociceptive circuit is okolovodoprovodnoe gray matter of the midbrain (TSSV), which includes a large number of enkefalinovyh neurons with opiate receptors. Proximity to the structures through which the afferent fibers ascending nociceptive tracts, allows to receive projections from the spinal sensory tracts, as well as from the ascending reticular formation. An important area of antinociceptive systems are the core suture stem and midbrain. Neurons seam nuclei receive direct fibers from TSSV, and their axons are included in the ascending and descending bundles. Descending fibers of these nuclei terminate in the posterior horns of the spinal cord. Along with top-down system of nuclei seam there is a system downstream of the nuclei of the reticular formation of the brain that plays a significant role in the modulation of pain. This system, unlike the axons nuclei seam is closed not only on the neurons of posterior horn, but the lateral and anterior horns, which affects the autonomic and motor activity. Major role in the regulation of pain sensitivity belongs to the lateral reticular nucleus, one of the functions of which is a constant tonic inhibitory impulses.
The primary locus of interaction of nociceptive and antinociceptive systems are rear horn of the spinal cord, where the closing of “pain” and “nebolevoy” sensitivity. Therefore, the transfer of nociceptive signals can initially be changed at the level of the spinal cord (rear horn), resulting in an upward flow of impulses of a new quality.
Narcotic analgesics play an important role in analgesia at the level of the spinal cord, as well as to activate the flow of descending impulses antinociceptive system.
Most narcotic analgesics act in a nonspecific way mnogoneyronny nociceptive system. Drugs inhibit conduct pain impulses to nonspecific nuclei of the thalamus, hypothalamus, amygdala complex (lower autonomic and emotional responses to pain, increase the threshold of pain endurance) and to a lesser extent, affect the neurons of posterior horn of the spinal cord, raising the threshold of pain sensitivity. Strong analgesics (fentanyl, lofentanil, buprenorphine, etc.) expressed an inhibit pain impulses and specific nociceptive path. Under the influence of morphine-like substances inhibited the flow of pain impulses in the thalamus, reticular formation, inhibited them in the cerebral cortex. Of great importance in the formation and regulation of pain is the thalamus. Three main thalamic nuclear complex involved in the integration of pain: ventrobazalny complex, posterior group of nuclei, medial and intralaminar nuclei. Posterior group nuclei of neurons respond to painful stimulation of the skin and pulp of the tooth, facilitate the transfer and evaluation of the localization of pain impact. Medial and intralaminar nuclei perceive somatic, visceral, auditory, visual and painful stimuli. They are also involved in the perception of painful stimuli, the pulp of the tooth. This group of nuclei plays an important role in the integration of “secondary”, poorly localized pain: they form a complex vegetomotornye and protective responses to pain, as well as behavioral manifestations of it. Morphine-like substances inhibit conduct pain impulses only in the thalamus. The perception of other sensory modalities (sound, light), they do not eliminate (even in large doses).
Since opiate receptors are located not only in the ways of pain, but also in the cerebral cortex, hypothalamus, hippocampus, amygdala and other brain regions, narcotic analgesics are given multiple psychotropic effects: pronounced sedation (calming), euphoria, hallucinations, etc. increases the portability pain varies significantly emotional coloring of pain, anxiety disappears, the expectation of pain. All this is largely due to the sedative properties of drugs, a state of euphoria (good, pleasant mood), subjective feeling of physical and mental peace, spiritual comfort, and ultimately leads to inhibition of negative emotional expressions of pain.
Euphoria is one of the main causes of addiction. The desire to reproduce that state forces to search for repeated contacts with the drug (without medical indications) and causes mental and physical dependence on the drug. It is believed that narcotic analgesics, activating the “opiate” receptors, on the principle of feedback and inhibit the release of endogenous peptides. After the abolition of narcotic analgesics, and there is insufficient endogenous peptide, and, of course, the medication injected. We develop the withdrawal syndrome (the phenomenon of “deprivation”), manifested in the form of mental, autonomic, cardiovascular and other changes. Autonomic disorders include dacryo and salivation, sweating, dilated pupils, nausea, vomiting, diarrhea, tachycardia, muscle pain, paresthesia and other mental manifestations are sleep disturbance, anxiety, hallucinations, an irresistible attraction to the drug. To prevent and eliminate the symptoms of an addict is constantly striving to take a drug that contributes to mental and physical dependence.
The danger of dependence limits the use of narcotic analgesics. In addition, when re-applying regularly develops addictive (weakening of the action), so for all the effects required high doses. Especially pronounced habituation to such effects as analgesia, euphoria and respiratory depression, but not to the “pupillary” and “lock” the action (eg, morphine), so the drug is characterized by pinpoint pupils, and habitual constipation.
A classic representative of the narcotic analgesic is morphine. It can cause depression of the central nervous system, relieves pain of various genesis. Title emudali in honor of the son of Greek god of sleep Morpheus.
Opium (frozen milky juice of unripe poppy-sleepy heads) – the main source of morphine from prehistoric times been used in medical practice.
In Chinese, Arabic, Indian medicine already in the XV-XVI centuries it was used as protivoponosnoe and intoxicants. Opium contains more than 20 alkaloids, which are in chemical structure are either derivatives piperidinfenantrena – have the properties of narcotic analgesics (morphine, codeine) or isoquinoline (papaverine, etc.) – have myotropic antispasmodic effect on smooth muscles of internal organs and blood vessels. Narcotic analgesics originally divided into:
1) natural, derived from opium – morphine, codeine, omnopon;
2) synthetic-trimeperidin hydrochloride (Promedolum), fentanyl, pentazocine (leksir, Fortran), Piritramide (dipidolor), tramadol (tramal).
Analgesics, extracted from opium, called opiates, and synthetic substitutes – opioids or opiatopodobnymi means.
On the selectivity and nature of the impact on opiate receptors narcotic analgesics are divided into:
1) agonists: morphine, trimeperidin hydrochloride (Promedolum), fentanyl, Piritramide (dipidolor) – are used as painkillers;
2) agonists-antagonists: pentazocine (used as an analgesic), Nalorphine is used at a moderate overdose of narcotic analgesics (excluding pentazocine);
3) antagonists: naloxone, naltrexone (are antagonists of all analgesics, including pentazocine).