Treatment of nociceptive back pain

Treatment of nociceptive pain syndrome involves three aspects:

• restriction of nociceptive flow in the central nervous system from the lesion focus,
• Suppression of synthesis and secretion of algogens,
• activation of antinociception.

Limitation of nociceptive impulses

From the focus of damage is achieved using local (local) anesthetics, the most popular of which are procaine (novocain), lidocaine. The mechanism of their action is the blockade of the sodium channels of the membrane of the neuron and its processes. Without the activation of the sodium system, it is impossible to generate an activity potential and, consequently, a nociceptive impulse.

For the interruption of nociceptive afferentation, methods of blocking the conduction along the peripheral nerves and the spinal cord are used. In this manual, we are not aiming at a detailed presentation of the corresponding techniques, they are detailed in the special literature on the methods of anesthesia. We briefly report on the methods of blockade used:

• Surface anesthesia
• Infiltration anesthesia
• Regional anesthesia (blockade of peripheral nerves)
• Central blockade

Surface anesthesia pursues the goal of blocking the excitation of nociceptors, when the cause that caused the pain is localized superficially in the skin. In general therapeutic or neurological practice, it is possible to use infiltration by the type of "lemon peel" 0.5-0.25% solution of novocaine. It is possible to use local anesthetics in the form of ointments and gel.

Infiltration anesthesia is used to inject an anesthetic into the deeper layers of the skin and skeletal muscles (eg, myogenic grigger zones). The use of procaine is most preferred.

Regional anesthesia (peripheral nerve blockade) should be performed by specialists with specialized training. Severe complications of peripheral nerve blockade include apnea, cardiovascular depression and epileptic seizures. For early diagnosis and successful treatment of severe complications, it is necessary to adhere to the same basic monitoring standards that are adopted for general anesthesia. Currently, blockade of the brachial plexus (supraclavicular and subclavian walk) is used. Blockade of intercostal nerves, musculocutaneous nerve, radial, medial and ulnar nerves, digital nerves of the upper limb, intravenous regional anesthesia of the upper limb but Biru, blockade of the femoral, blocking, selalistic nerves. Blockade of the nerves in the popliteal fossa, regional anesthesia of the foot, intravenous regional anesthesia of the lower extremity according to Biru, blockade of the intercostal nerves, cervical plexus, paravertebral thoracic blockade, blockade of the ilio-inguinal, ilio-hypogastric, femoral-genital nerves, infiltration anesthesia of the penis.

Spinal, epidural and caudal anesthesia suggests the introduction of a local anesthetic in the immediate vicinity of the spinal cord, so they are united under the term "central blockade."

Spinal anesthesia is the injection of a local anesthetic solution into the subarachnoid space of the spinal cord. It is used for operations on the lower limbs, hip joint, perineum, lower abdominal floor and lumbar spine. Spinal anesthesia can be performed only in the operating room, fully equipped with monitoring equipment, general anesthesia and resuscitation.

Unlike spinal anesthesia, which results in a complete blockade, with epidural anesthesia, there are options from analgesia with a weak motor blockage to deep anesthesia with complete motor blockade, depending on the choice of anesthetic, its concentration and dose. Epidural anesthesia is used for various surgical interventions, in the first stage of labor, for the treatment of postoperative pain. Epidural anesthesia can be performed only on condition that the equipment and medicines necessary for the treatment of possible complications are fully provided, from mild arterial hypotension to circulatory arrest.

Caudal anesthesia involves the introduction of an anesthetic through the sacral cleft - the medially located bone defect in the lowest part of the sacrum, which is covered by a dense sacrococcygeal ligament. In 5-10% of people, the sacral slit is absent, therefore, caudal anesthesia is impossible. Like the epidural space of the lumbar spine, the sacral canal is filled with a venous plexus and a loose connective tissue.

Suppression of synthesis and secretion of algogenes

One of the mechanisms of peripheral sensitization and primary hyperalgesia is the synthesis and secretion of algogens in the lesion focus. When tissues are damaged, phospholipase A2 metabolizes the phospholipids of cell membranes to arachidonic acid, which in turn is oxidized by the enzyme cyclooxygenase (COX) to cyclic endoperoxides, converted by prostaglandin isomerase, thromboxane synthetase and prostacyclin synthetase, respectively, into prostaglandins, thromboxane A2 and prostacyclins. Prostaglandins (PG) can both directly stimulate peripheral nociceptors (PGE2, PGI2) and sensitize them (PGE2, PGE1, PGF2a, PGI2). As a result of the enhancement of the afferent nociceptive flow into the structures of the spinal cord and brain, an NMDA-dependent increase in the concentration of intracellular calcium, a nascent activation of phospholipase A2, stimulates the formation of free arachidonic acid and the synthesis of prostaglandins in neurons, which in turn increases the excitability of the spinal cord receptor neurons. Inhibition of COX preparations, 01 belonging to the group of non-steroidal anti-inflammatory drugs (NSAIDs).

Despite the wide variety of non-steroidal anti-inflammatory drugs, all "standard" drugs in this class of drugs have common positive and negative properties. This is due to the universal molecular mechanism of their pharmacological activity, namely, inhibition of COX. There are two isoforms of COX: a "structural" COX-1 enzyme that regulates the production of PG that provides the physiological activity of cells and the inducible isoenzyme COX-2, which takes part in the synthesis of PG in the inflammatory focus. It has been shown that the analgesic effects of NSAIDs are determined by the inhibition of COX-2, and the side effects (gastrointestinal tract damage, renal dysfunction and platelet aggregation) are inhibited by COX-1. There are data on the mechanisms of the analgesic activity of NSAIDs. These include: central opioid-like antinociceptive action, blockade of NMDA receptors (increase in the synthesis of kynurenic acid), changes in the conformation of G-protein subunits, suppression of afferent pain signals (neurokinins, glutamate), increased serotonin content, anticonvulsant activity.

At present, selective inhibitors of COX blocking both enzyme isoforms and "selective" COX-2 inhibitors are used in clinical practice. According to the recommendations of FDA (2005), COX-2 selective NSAIDs are coxibs; COG-2 nonselective non-steroidal anti-inflammatory drugs are Diclofenac, Diflunisal, Etodolac, Fenoprofen, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Ketorolac, Mefenamic Acid, Meloxicam, Nabumetone, Naproxen, Oxaprozin, Lornoxicam, Piroxicam, Salsalate, Sulindac, Tolmetin.

According to the recommendations for the use of non-steroidal anti-inflammatory drugs (2009), selective COX-2 inhibitors include coxibs and some other NSAIDs (meloxicam, nimesulide, nabumeton, ethololac).

Diclofenac sodium remains the "gold standard" among traditional NSAIDs, having all the necessary dosage forms - injectable, tableted and candles. According to the "risk-benefit" ratio, diclofenac occupies an intermediate position between coxibs and other traditional NSAIDs.

Despite differences in the selectivity of the drugs, the FDA has developed general guidelines for the use of COX inhibitors:

• The increase in cardiovascular complications is recognized as possible with the use of the entire class of NSAIDs (excluding low doses of aspirin)
• It is recommended to add additional warnings about the possibility of developing cardiovascular and gastrointestinal complications in the instructions of all NSAIDs. Both selective and traditional, including non-prescription forms
• When all NSAIDs are prescribed, it is recommended to use the minimum effective dose as short a period of time
• All manufacturers of traditional NSAIDs should provide a review and clinical trial results for subsequent analysis and evaluation of cardiovascular risks when taking NSAIDs
• These solutions apply to OTC-free forms of NSAIDs

In 2002, DLSimmons et al. Reported the discovery of the third isoform of cyclooxygenase-COX-3, which is expressed predominantly in neurons and does not directly participate in tissue inflammation, plays a role in the modulation of pain and the genesis of fever, and the specific inhibitor of COX-3 is acetaminophen.

Acetaminophen has an analgesic effect without a significant local anti-inflammatory component, is among the non-opioid analgesics recommended by WHO for the treatment of chronic pain, including cancer. As an analgesic, it is somewhat inferior to NSAIDs and mstamisole, but can be used in combination with one of them with the best rc.

Metamizole sodium has a good analgesic effect, comparable with the effect of NSAIDs, but differs from the latter with a mild anti-inflammatory effect. In many foreign countries metamizole is banned for clinical use due to possible fatal hematotoxic reactions with long-term therapy (agranulocytosis). However, severe complications, including fatal outcome, are possible with the use of NSAIDs (NSAIDs induced bleeding, kidney failure, inafilactic shock) and paracetamol (hepatic insufficiency, anaphylaxis). The rejection of the clinical use of metamizole at this stage should be considered premature, as it expands the possibilities of non-opioid therapy for acute and chronic pain, especially in contraindications to the administration of NSAIDs and paracetamol .The side effects of metamizole may be manifested by sclerotic reactions of varying severity, oppression of hemopoiesis (agranulocytosis) impaired renal function (especially in dehydrated patients.) Do not simultaneously appoint metamizole and NSAIDs because of the risk of combined nephros nical action presents.

At present, the classification of non-narcotic analgesics with respect to COX isoforms is as follows

Drug Groups	Example
Non-selective isciters of COX	NSAIDs, acetylsalicylic acid in high doses
Selective inhibitors of COX-2	Coxiba, meloxicam, nimesulide, nabumethon, etodolac
Selective inhibitors of NOOG-3	Acetaminophen, metamizole
Selective inhibitors of COX-1	Low doses of acetylsalicylic acid (blocks COX-1 dependent aggregation Thrombocytes, but does not have anti-inflammatory and analgesic activity)

Activation of antinociception

The shift in the balance between the activity of the nociceptive and antinociceptive systems towards the latter is possible with pharmaceuticals belonging to different classes, either by suppressing the secretion of excitatory amino acids (glutamate aspartate) or by activation of the secretion of inhibitory (GABA).

Widespread use in the therapy of somatogenic pain was found in agonists a _2- adrenoreceptors. One of the most effective and safe drugs of this series is tizanidine. Its analgesic effect is associated with activation of spinal presynaptic a _2- adrenoreceptors, which limits the secretion of excitatory amino acids from the central terminals of nociceptors. The undoubted positive property of tizanidine is the presence of a sedative effect, which is important for the normalization of sleep in patients with acute and chronic pain. In addition, the drug has a gastroprotective effect, due to inhibition of gastric secretion. Recently, a form of tizanidine with a slow (modified release - Sirdalud MR (Sirdalud MP) was registered in Russia.The capsule contains 6 mg of tizanidine, which is slowly released within 24 hours.The pharmacokinetics of the drug is more favorable than in conventional sirdaloud, since it allows maintaining the optimal concentration drug in the blood for a longer time, without high peak concentrations, causing drowsiness.

Thus, simultaneous suppression of peripheral and central sensitization, simultaneous administration of NSAIDs and Tizanidine, which simultaneously neutralizes gastrotoxicity, has a sedative and miorelaxing effect.

Activation of antinociception is also possible by potentiating GABA-ergic transfer with benzodiazepines. The presence of two types of benzodiazepine receptors is established, type 1 receptors prevail in the cerebellum, pallor balloon and cerebral cortex, and type 2 receptors in the caudate nucleus and the shell. In the implementation of anxiolytic activity, type 1 receptors are involved, and type 2 mediates the anticonvulsant effect of benzodiazepines. Benzodiazepine receptors are localized on postsynaptic membranes of GABAergic CNS systems. Activation of the GABA receptor released by the neurotransmitter leads to the discovery of this channel, an increase in the membrane permeability for chlorine and, consequently, to the hyperpolarization of the postsynaptic membrane leading to an increase in cell resistance to the exciting signals. Benzodiazepines prolong the possibility of the existence of open ion channels in response to the effect of GABA. Without affecting the number of channels and the movement of chloride ions.

Recently, much attention has been paid to the magnesium deficiency in the genesis of neurological disorders. The magnesium ion is a physiological blocker of the calcium channels associated with NMDA receptors. Magnesium deficiency is manifested by sensitization of receptors, including nociceptors, which can be manifested by paresthesia, sensation of neurons of the central nervous system (restless legs syndrome, increased muscle contractility, convulsions, musculoskeletal abscess). An effective corrector of magnesium deficiency is the preparations containing organic magnesium salts, for example, magnesium lactate (Magnelis B6). Organic magnesium salts have high bioavailability in the absence of side effects. Clinical experience indicates the need to correct magnesium deficiency in chronic pain.