Neuropathic pain

Neuropathic (neurogenic) pain as a kind of chronic pain is caused by damage to the peripheral or central nervous system, or a disease that affects any sensitive nerves or central ganglia. Examples: lumbar pain, diabetic neuropathy, postherpetic neuralgia, post-traumatic central or thalamic pains and post-mutant phantom pain.

Neuropathic pains are usually classified based on the etiological factor causing damage to the nervous system, or based on anatomical localization of pain (trigeminal, lumbosacral, intercostal neuralgia). Neuropathic pain is characterized by a complex of negative and positive syndromes. Syndromes of prolapse are manifested by sensory deficiency in the form of complete or partial loss of sensitivity in the zone of innervation of the affected nerves. Positive symptoms are characterized by the presence of spontaneous pain in combination with dysesthesia and paresthesia.

Neuropathic pain has a number of characteristics that distinguish it, clinically and pathophysiologically from nociceptive pain (Bowsher, 1988):

1. Neuropathic pain has the character of dysesthesia. Pathognomonic characteristics for it are the definitions: burning and shooting pain (more often - blunt, pulsating or pressing).
2. In the vast majority of cases of neuropathic pain, there is a partial loss of sensitivity.
3. Typical are vegetative disorders, such as decreased blood flow, hyper- and hypohydrosis in the pain area. The pain often intensifies or causes emotional-stress disorders.
4. Usually marked allodynia (meaning pain in response to low-intensity, in normal conditions, not causing pain, irritants). For example, a light touch, a whiff of air, or combing with trigeminal neuralgia causes a "painful volley" in response (Kugelberg, Lindblom, 1959). More than a hundred years ago, Trousseau (1877) noted the similarity between paroxysmal shooting pain in trigeminal neuralgia and epileptic seizures. Now it is known that all shooting neurogenic pains can be treated by anticonvulsants (Swerdlow, 1984).
5. An inexplicable feature of even severe neuropathic pain is that it does not prevent the patient from falling asleep. However, even if the patient falls asleep, he suddenly wakes up from severe pain.
6. Neurogenic pain is not susceptible to morphine and other opiates in conventional analgesic doses. This demonstrates that the mechanism of neurogenic pain is different from opioid-sensitive nosigenic pain.

Neuropathic pain is represented by two main components: spontaneous (stimulo-dependent) pain and induced (stimulependent) hyperalgesia. Spontaneous pain can be permanent or paroxysmal. In most patients, spontaneous pain is associated with activation of nociceptive C-fibers (primary nociceptors), which are peripheral terminals of the first sensitive neurons (primary providers) whose bodies are located in the posterior root ganglion. Spontaneous pain is divided into two types: sympathetically independent pain and sympathetically sustained pain. Sympathetically independent pain is associated with activation of primary nociceptors as a result of damage to the peripheral nerve and disappears or significantly regresses after local blockade with an anesthetic of the damaged peripheral nerve or the affected area of the skin, it usually has a shooting, lancinating character. Sympathetically sustained pain is accompanied by changes in blood flow, thermoregulation and sweating, motor disorders, trophic changes in the skin, its appendages, subcutaneous tissues, fascia and bones, is more difficult to treat.

Hyperalgesia is the second component of neuropathic pain. It is usually associated with activation of thick myelinated A-fibers against the background of central sensitization (normal activation of A-fibers is not associated with pain sensations). Depending on the type of stimulant, hyperalgesia may be thermal, cold, mechanical, or chemical. By localization, primary and secondary hyperalgesia are isolated. Primary hyperalgesia is localized in the innervation zone of the damaged nerve or in the tissue injury zone, it occurs mainly in response to irritation of sensitized peripheral nociceptors as a result of damage. The process also involves the category of nociceptors, called "dormant", which are normally not active.

Secondary hyperalgesia is more widespread, far beyond the innervation zone of the damaged nerve. Due to the increased excitability of sensitive neurons of the posterior horns of the spinal cord associated with the zone of innervation of the damaged nerve, sensitization of nearby intact neurons with expansion of the receptive zone occurs. In this regard, irritation of intact sensory fibers that innervate healthy tissues surrounding the injury zone, triggers the activation of secondary sensitized neurons, which is manifested by pain - secondary hyperalgesia. Sensitization of the neurons of the posterior horns leads to a decrease in the pain threshold and the development of applause, i.e. To the appearance of painful sensations for irritation, which in normal cases is not accompanied by them (for example, tactile). Changes in the excitability of the central parts of the nociceptive system associated with the development of secondary hyperalgesia and allodynia are described by the term "central sensitization". Central sensitization is characterized by three signs: the appearance of a zone of secondary hyperalgesia, the intensification of the response to suprathreshold stimulations, the appearance of a response to subthreshold stimulation. These changes are clinically manifested by hyperalgesia on pain stimuli, which are much wider than the damage zone, and include the onset of hyperalgesia on neo-stimulation.

Primary and secondary hyperaplegia are heterogeneous. Primary hyperalgesia is represented by three types - thermal, mechanical and chemical, secondary hyperalgesia - mechanical and cold. A clinical examination aimed at identifying various types of hyperalgesia may allow not only to diagnose the presence of pain neuropathy syndrome, but also to analyze the pathophysiological mechanisms of the development of pain and hyperalgesia based on the analysis of these data. Pathophysiological mechanisms of pain and hyperalgesia are very diverse and are being actively studied.

Currently, there are no treatments that would prevent the development of neuropathic pain, there are also no highly effective and specific drugs that allow controlling its manifestations. The goal of drug therapy is, first of all, reducing the intensity of pain, which helps, as early as possible, to begin active restorative treatment.

[1], [2], [3], [4], [5], [6], [7]