RU2208437C2 - Method of treatment of pain syndrome - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: invention relates to methods of efferent surgery and can be used in treatment of patients with pain syndromes. Method involves taking off 300 ml of blood, its centrifugation at 1800 rev/min for 15 min followed by removal of supernatant plasma and addition of 1 ml of ATP and then 1 ml of diclofenac preliminary mixed with 2 ml of ascorbic acid to remained cellular mass. Obtained mass is incubated with indicated medicinal preparations at constant shaking followed by reinfusion of autogenic cellular mass by intravenous route by drops. Treatment course is 3-5 procedures with interval for 24 h. Invention promotes to the enhancement of effectiveness of treatment of patients with pain syndrome of vertebrogenic and arthrogenic origin and pain syndrome in inflammatory diseases of visceral organs. EFFECT: enhanced effectiveness of method. 1 tbl, 1 ex

Description

 The treatment method relates to medicine, namely to methods of efferent surgery, and can be used to treat patients with severe pain of vertebrogenic, arthrogenic nature or pain in inflammatory diseases of internal organs.

 Over the past decades, in most industrialized countries, there has been a significant increase in the number of patients with prolonged, recurrent and chronic pain syndromes of various origins. According to epidemiological studies, such patients make up about 45% of the population. Chronic pain is characterized by the development of specific neurophysiological reactions in the body and an increase in the influence of personality-psychological factors on the course of the pathological process, the negative value of which is realized in increasing the patient's resistance to treatment.

 With the transition of pain into a chronic form, its physiological significance is largely lost and it becomes dangerous and even life-threatening. The strength of visceral pain, as a rule, does not correspond to the degree of tissue damage, as it is caused by stretching or chemical irritation of hollow organs, vascular legs and capsules. The picture of pathological pain is associated with impaired coordination of the nociception process.

 In gynecological patients, a special painful condition is identified, which is called pelvic pain syndrome. This is a polyetiological process with complex pathogenesis, the clinical picture of which has a number of characteristic features - manifestations of "pathological pain", "pain-disease" prevail in it. Moreover, patients have constant pain in the lower abdomen and lower back of varying intensity and color, prone to irradiation. Periodically occurring exacerbations of pain crises are provoked by cooling, overwork, psychological stress or exacerbation of diseases of internal organs (G. A. Savitsky et al. Surgical treatment of pelvic pain syndrome in a gynecological clinic. St. Petersburg -2000. -S. 26-31).

 A known method of treating pain with aspirin. Aspirin is often used for headaches, somatic pain, accompanying diseases of the musculoskeletal system, and other visceral pains, both light and moderate. For example, in the USA, many rheumatologists, when choosing a medicine at the initial stage of treatment, prefer aspirin. The drug is used in doses of 600-900 mg 4 times a day (D.G. Graham-Smith, J.K. Aronson. Oxford Handbook of Clinical Pharmacology and Pharmacotherapy. - M., Medicine. - 2000. - S. 436, 481 )

 Many therapeutic and side effects of aspirin are associated with suppression of the conversion of arachidonic acid to cyclic endoperoxides, inhibiting the enzyme cyclooxygenase (COX), while the production of prostaglandins decreases. In inflammatory processes, the release of prostaglandins is the main pathophysiological mechanism. They are involved in the development of hyperplasia, erythema, exudation, like other inflammatory mediators. As the inflammatory response decreases, the pharmacological effect is manifested by a decrease in pain (ibid., P. 435).

 The most common adverse reactions after taking aspirin are from the gastrointestinal tract. Damage to the mucous membrane of the stomach and intestines, as well as dyspeptic symptoms, are noted. In the mucous membrane of the gastrointestinal tract, along with hyperemia and individual hemorrhages, ulcerations are observed, sometimes multiple, as well as perforating ulcers. Moreover, these injuries occur after a single use of drugs. This is due to the inhibition of COX and the suppression of prostaglandin synthesis in the gastric mucosa, which leads to disruption of its blood supply and accelerated desquamation of the epithelium, increased acidity of the gastric juice and its digestive activity. Other complications include inhibition of platelet aggregation, nephro- and hepatotoxicity, as well as impaired attention and speed of reaction (Y. A. Sigidin, G. Ya. Schwartz, A. P. Arzamastsev. Drug therapy for the inflammatory process // M., Medicine. -1988. - S. 108, 132).

 There is a known method of treating pain syndrome, which we adopted as a prototype, using diclofenac, which exceeds the analgesic effect of aspirin by 31 times, while the safety index (ratio of effective and ulcerogenic doses) for diclofenac is 1.2, and for aspirin - 0.91 ( ibid., pp. 62-64). Diclofenac is prescribed in a therapeutic dose of 75 mg (3 ml) IM 1-2 times a day for no more than 2 days, then they switch to oral administration of the drug 25 mg 2-3 times a day.

 Diclofenac, due to the effect on the biologically fixed mechanisms of the inflammatory process, occupies a definite place in the treatment of not only arthritis, but also inflammatory diseases of the uterus. Non-specifically suppressing the inflammatory process, it is able to exert a pathogenetic effect, although it acts on the secondary links of pathogenesis, i.e. at the level of the already developed pathological process (A. N. Strizhakov, N. M. Podzolkova. Purulent inflammatory diseases of the uterine appendages // M., Medicine. - 1996. - P. 142-144).

At the same time, the same negative moments are characteristic for diclofenac as for aspirin, although they are less pronounced:
- "ceiling" effect - i.e. the lack of increased effect after exceeding a certain dose of the drug,
- ulcerogenic effect,
- inhibition of platelet aggregation,
- nephro- and hepatotoxicity,
- violation of attention and speed of reaction.

 The objective of the invention is to increase the effectiveness of the treatment of patients with severe pain of vertebrogenic, arthrogenic nature or pain in inflammatory diseases of the internal organs.

 This object is achieved by preliminarily collecting 300 ml of blood, centrifuging it at 1800 rpm for 15 minutes, followed by removal of the supernatant plasma and introducing 1 ml of ATP and 1 ml of diclofenac pre-mixed with 2 ml of ascorbic acid into the remaining cell mass. acids, they incubate the obtained cell mass with the indicated drugs for 30 minutes with constant shaking, after which the autogenous cell mass is reinfused intravenously, while the course of treatment is 3-5 procedures with an interval of 48 hours

 The novelty of the method.

The course of reinfusion of autologous cell mass of blood incubated extracorporeally with ascorbic acid and diclofenac provides:
1. Strengthening the analgesic effect of diclofenac with a decrease in side effects in comparison with the traditional route of administration.

 2. The increase in the duration of action of diclofenac in comparison with the traditional route of administration.

 3. The introduction of diclofenac into the cell mass of blood together (in the same syringe) with ascorbic acid and in a ratio of 1: 2 avoids the hemolysis observed with intravenous administration of the drug.

 4. The combined administration of ATP and diclofenac with ascorbic acid provides a more pronounced analgesic effect than when administered separately in the blood mass.

 5. The interval between procedures 2 days is selected based on the half-life of diclofenac from the patient’s blood.

 The essence of the method is as follows.

When a patient with an arthrogenic, vertebrogenic pain syndrome or with an inflammatory disease of an internal organ arrives, 300 ml of blood (up to 8% of the circulating blood volume) is taken from him into a sterile vial with 5 thousand units of heparin per 50 ml of physiological saline. After that, the blood is centrifuged at 1800 rpm for 15 minutes, followed by removal of the supernatant plasma (centrifugal plasmapheresis). In the remaining cell mass of blood, 1 ml of ATP is successively injected, then diclofenac (1 ml), previously mixed with ascorbic acid 2 ml (in one syringe), the resulting mixture is incubated at a temperature of 18-24 ^o C for 30 min with constant shaking of the bottle . The return of the incubated mixture into the bloodstream of the patient is carried out intravenously. The course of treatment is 4 sessions. The interval between the procedures is two days.

To justify these modes, the following provisions are given:
1. The volume of 8% of BCC does not cause a patient with rheological and hemodynamic disorders, as well as significant changes in biochemical parameters.

 2. ATP at a dose of 1 ml added to the cell mass, as shown by us, activates the phagocytic activity of leukocytes, increasing the average number of phagocytic leukocytes by half.

 3. Fractional plasmapheresis helps to improve tissue respiration and increase cellular metabolism, which leads to the restoration of organ function with the participation of NSAIDs.

 4. Plasmapheresis leads to a thickening of the cellular mass of blood, which increases the possibility of "loading" the cellular elements of the blood with drugs. It was previously noted that the binding ability of cell organelles depends on the ratio between the volume of the liquid medium and the volume of the organelles themselves. Moreover, an increase in the volume of the latter increases their ability to bind the drug (Shvetsov D.A. Directional transport of antibiotics in the treatment of acute nonspecific inflammatory diseases of the lungs and pleura. Abstract of candidate of medical sciences Karaganda 1996).

 5. The interval between the procedures was chosen empirically, based on the fact that, based on our experience, the clinical effect of the introduction of NSAIDs in this way lasts about 48 hours.

 6. The addition of ascorbic acid to diclofenac in a ratio of 2: 1 is necessary to reduce the pH of the drug to values that do not cause erythrocyte hemolysis. This position is based on the fact that diclofenac is capable of a number of transformations both in vivo and in vitro, primarily to cyclization with the formation of 2,6-dichlorophenylindolinone, the precursor in the synthesis of orthophene. Similar changes can occur in the process of obtaining dosage forms of diclofenac, for example, when the pH changes to the acid side (Y. A. Sigidin, G. Ya. Schwartz, A. P. Arzamastsev. Drug therapy of the inflammatory process // M., Medicine. - 1988.-S.-159-160).

 We have treated 78 patients with pain syndrome of various origins. The treatment results are presented in the table.

 Clinical example.

 Patient S., 44 years old, with complaints of pain in the lumbosacral spine with irradiation along the posterolateral surface of the left leg, numbness of the left foot (outer edge and little finger).

 Disease history: Vertebrogenic history since 1994. The deterioration of health since the spring of 1997 was treated on an outpatient basis, after a course of acupuncture and manual therapy it became worse. Long-term outpatient and inpatient treatment did not stop the pain syndrome. In May 1998, she was operated on for a herniated disc L5-L6, after which she was treated on an outpatient basis and in a hospital. Since February 1999, pain in the lower back and right leg appeared, was treated on an outpatient basis and in a hospital. In November 1999, increased pain in the lower back and left leg. Hospitalized in the neurological department.

 Outpatient: X-ray of the lumbar spine - osteochondrosis of the lumbosacral spine. Posterior spondylolisthesis L6 up to 2 mm, non-shortened arches S1.

 Computed tomography of the spine L6-S1 1-2 tbsp. transitional L6 spine with compression L6-S1 in the back, on the left. Spondylarthrosis L6-S1 1 degree.

 Electromyography - signs of radiculopathy of the roots of L5-S1 on the left.

 OBJECTIVE STATUS: Condition is satisfactory. The food is satisfactory. The skin is clean, vesicular breathing in the lungs, no wheezing. Heart sounds are distinct, rhythmic, blood pressure is 100/80 mm Hg. The abdomen is soft, painless on palpation. Stool, diuresis is normal.

NEUROLOGICAL STATUS: Clear consciousness, active behavior, full movement of eyeballs, no nystagmus. Isocoria. Easy asymmetry of the nasolabial folds. Paravertebral points are painful in the lumbar region from 2 sides. Lordosis at the lumbar level is smoothed. Long muscles of the lower back are strained. Limitation of range of motion in the lower back. Tendon reflexes on the hands are equal. Knee reflexes of average vivacity are equal, Achilles, plantar reflexes on the left are absent. The left gluteal fold sags. Symptom Lasega - 45 ^o on the left and 60 ^o on the right. Sensitive disorders - left hypesthesia on the root of the L5-S1. In the Romberg position is stable. Coordination tests are satisfactory.

 DIAGNOSIS: Osteochondrosis of the lumbar spine, chronically recurrent type of course, acute phase, Art. stabilization. Posterolateral herniation of the intervertebral disc L6-S1 on the left. Posterior spondylolisthesis L6. Condition after surgery for disc herniation L5-L6, cicatricial commissural epiduritis.

 CM compression of the root L5-S1 on the left, irritatively deficient stage, 3 tbsp. severity of clinical manifestations.

TREATED: 300 ml of blood was taken from a cubital vein into a sterile vial with 5 thousand units of heparin per 50 ml of physiological saline. After that, the blood was centrifuged at 1800 rpm for 15 minutes, followed by removal of the supernatant plasma. 1 ml of ATP was successively introduced into the remaining cell mass of blood, then diclofenac (1 ml), pre-mixed with ascorbic acid (2 ml in one syringe), the mixture was incubated at a temperature of 18-24 ^° C for 30 min with constant shaking of the vial . The return of the incubated mixture into the bloodstream of the patient was carried out intravenously. The course of treatment was 4 sessions. The interval between the procedures was two days.

 After the first session, the patient noted a decrease in pain, gradually the pain regressed. At the end of the course of treatment - the pain does not bother, numbness of the left foot persists.

 NEUROLOGICAL STATUS: Clear consciousness, active behavior, full movement of eyeballs, no nystagmus. Isocoria. Easy asymmetry of the nasolabial folds. Paravertebral points are almost painless. Lordosis at the lumbar level saved. There is no tension of the long muscles of the lower back. The range of motion in the lower back is full. Tendon reflexes on the hands are equal. Knee reflexes of average vivacity are equal, Achilles, plantar reflexes on the left are absent. Symptom Lasega is negative on both sides. Sensitive disorders - left hypesthesia on the root of the L5-S1. In the Romberg position is stable. Coordination tests are satisfactory.

The positive effect of the proposed method:
1. Significant suppression of pain, and in some cases their complete disappearance.

 2. A significant decrease (two or more times), and in some cases, the abolition of the maintenance daily dose of analgesics.

 3. Reducing the frequency and severity of side effects of drug therapy.

 4. The absence of repeated hospitalizations in the hospital during the year.

Claims (1)

 A method for the treatment of pain of a vertebrogenic, arthrogenic nature or for inflammatory diseases of internal organs, comprising drug treatment with diclofenac, characterized in that 300 ml of blood are preliminarily collected, centrifuged at 1800 rpm for 15 minutes, followed by removal of the supernatant plasma and sequential administration in the remaining cell mass of 1 ml of ATP and then 1 ml of diclofenac, pre-mixed with 2 ml of ascorbic acid, the resulting mass is incubated with the indicated drug with continuous shaking, followed by reinfusion of autogenous cell mass by intravenous drip, and the course of treatment is 3-5 procedures with an interval of 48 hours.

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