Neuropathic pain

Neuropathic (neurogenic) pain as a type of chronic pain is caused by damage to the peripheral or central nervous system, or by a disease affecting any sensory nerves or central ganglia. Examples: low back pain, diabetic neuropathy, postherpetic neuralgia, posttraumatic central or thalamic pain, and postamputation phantom pain.

Neuropathic pain is usually classified based on the etiologic factor causing damage to the nervous system or based on the anatomical localization of pain (trigeminal, glossopharyngeal, intercostal neuralgia). Neuropathic pain is characterized by a complex of negative and positive syndromes. Loss syndromes are manifested by sensory deficit in the form of complete or partial loss of sensitivity in the innervation zone 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 features that distinguish it, both clinically and pathophysiologically, from nociceptive pain (Bowsher, 1988):

1. Neuropathic pain has the character of dysesthesia. The following definitions are considered pathognomonic characteristics for it: burning and shooting pain (more often - dull, pulsating or pressing).
2. In the vast majority of cases of neuropathic pain, partial loss of sensitivity is observed.
3. Vegetative disorders are typical, such as decreased blood flow, hyper- and hypohidrosis in the painful area. Pain often intensifies or itself causes emotional and stressful disorders.
4. Allodynia (meaning pain sensation in response to low-intensity, normally painless stimuli) is usually observed. For example, a light touch, a puff of air, or combing the hair in trigeminal neuralgia causes a "pain 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. It is now known that all shooting neurogenic pains can be treated with anticonvulsants (Swerdlow, 1984).
5. An inexplicable characteristic 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 unresponsive to morphine and other opiates at usual analgesic doses, demonstrating that the mechanism of neurogenic pain is distinct from opioid-sensitive nociceptive pain.

Neuropathic pain is represented by two main components: spontaneous (stimulus-independent) pain and induced (stimulus-dependent) hyperalgesia. Spontaneous pain can be constant or paroxysmal. In most patients, spontaneous pain is associated with the activation of nociceptive C-fibers (primary nociceptors), which are peripheral terminals of the first sensory neurons (primary afferents), the bodies of which are located in the dorsal root ganglion. Spontaneous pain is divided into two types: sympathetically independent pain and sympathetically maintained pain. Sympathetically independent pain is associated with the activation of primary nociceptors as a result of damage to a peripheral nerve and disappears or significantly regresses after local blockade of the damaged peripheral nerve or affected skin area with anesthetic; it is usually shooting, lance-like in nature. Sympathetically supported pain is accompanied by changes in blood flow, thermoregulation and sweating, movement disorders, trophic changes in the skin, its appendages, subcutaneous tissues, fascia and bones, and is more difficult to treat.

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

Secondary hyperalgesia is more widespread, extending far beyond the innervation zone of the damaged nerve. Due to increased excitability of sensory neurons of the posterior horns of the spinal cord associated with the innervation zone of the damaged nerve, sensitization of nearby intact neurons occurs with expansion of the receptive zone. In this regard, irritation of undamaged sensory fibers that innervate healthy tissues surrounding the damaged zone causes activation of secondarily sensitized neurons, which is manifested by pain - secondary hyperalgesia. Sensitization of neurons of the posterior horns leads to a decrease in the pain threshold and the development of allodynia, i.e. to the appearance of pain sensations to irritation that is normally 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, an increase in the response to suprathreshold stimuli, and the appearance of a response to subthreshold stimulation. These changes are clinically manifested by hyperalgesia to pain stimuli, which extends much wider than the zone of damage, and include the occurrence of hyperalgesia to non-painful stimulation.

Primary and secondary hyperalgesia are heterogeneous. Primary hyperalgesia is represented by three types - thermal, mechanical and chemical, secondary hyperalgesia - mechanical and cold. Clinical examination aimed at identifying various types of hyperalgesia can not only diagnose the presence of pain neuropathy syndrome, but also, based on the analysis of these data, identify the pathophysiological mechanisms of pain and hyperalgesia. Pathophysiological mechanisms of pain and hyperalgesia are very diverse and are currently being actively studied.

Currently, there are no treatment methods that would prevent the development of neuropathic pain, nor are there highly effective and specific drugs that allow controlling its manifestations. The goal of drug therapy is, first of all, to reduce the intensity of pain, which helps to begin active rehabilitation treatment as early as possible.

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