FI115032B - A method of treating backache - Google Patents

Description

115032

A METHOD OF TREATING A BACK DISEASE

Field of the Invention

The present invention relates to the use of beta-blockers or nitrates in the treatment or prophylaxis of nonspecific back pain (back pain), osteoarthritis or other degenerative musculoskeletal disorders in mammals.

Background of the Invention

Back pain and osteoarthritis are common health problems in all developed countries. The most common form of back pain is the so-called non-specific or idiopathic or simple back pain that affects the majority of the population at some point in their lives. The discomfort is believed to be of mechanical origin and associated with physical exertion, although it often occurs spontaneously in the context of normal everyday activities. Nonspecific back pain rarely leads to severe dysfunction.

Almost everyone suffers from back pain at some point in their lives because lifetime prevalence is about 80% and monthly prevalence is 30-40%. Half of the population over the age of 30 suffers from recurrent back pain. 15 years of f! . According to a Finnish follow-up study, back pain has not increased. However, during the same period, there is a significant increase in the incidence of recurrent and chronic back pain. ·,: Statistics on absenteeism have been exponential. The reason for this development is degeneration. ' , radio-related morphological diagnoses, which are readily made by ever more accurate imaging techniques and because all individuals develop age-related changes, regardless of subjective ability, and thus, common spinal age-related changes are often associated with a common and apparently widespread symptom nothing to do with ongoing back disease.

For nonspecific back pain, there is a very clear research and treatment practice when comparing the effectiveness of treatment systems in different countries. America- 2 11503? Legal practice is very specialized and uses a lot of computer and magnetic resonance imaging as well as surgical treatment is often performed. In England, the treatment of back pain is focused on primary health care, including rest, medication and physical therapy. However, the results of both treatments are not good. The number of dissatisfied people (40-50%) is constantly increasing. As a result, the technical level of specialist services available for diagnostic and treatment outcomes does not appear to have any impact on the outcome of back pain treatment.

There is a widespread perception that treatment of nonspecific back pain is largely ineffective and inappropriate. On the other hand, it is possible for up to 70% of healthy individuals to detect changes in the septum using accurate imaging techniques, so it is very problematic to distinguish an abnormal finding from normal physiological variation. The structural change observed in the pictures may not be in any way related to the ongoing clinical symptom and pain.

The present invention is based on an extensive prospective population study that has established a link between atherosclerotic vascular disease and non-specific back pain and osteoarthritis. It has been found that atherosclerotic vascular disease is associated with back pain and that atherosclerotic vascular disease predicts future back pain. In addition, Doppler technology ensures blood. the relationship between circulatory deficits and back pain by measuring the intraocular space, ·,; microcirculation. It has been shown that local blood circulation is sore in the back. ·,: Less in comparison to healthy tissue and that of blood circulation recovery. · ·. is delayed in aching back after exertion.

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Summary of the Invention

The present invention is based on the finding that nonspecific back pain, osteoarthritis or other degenerative musculoskeletal disorders can be treated or prevented by providing the individual in need of treatment with an effective amount of nitrate or beta-blocker. The invention makes it possible to increase blood flow and tissue blood flow to musculoskeletal tissues and thereby reduce back pain or degenerative joint pain.

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Detailed Description of the Invention

Nitrates and beta-blockers with anti-ischemic activity are typically used to treat angina pectoris.

Nitrates and beta-blockers have vasodilating and antihypertensive effects.

Typical examples of beta-blockers include alprenolol, oxprenolol, pindolol, propranolol, timolol, asebutolol, atenollol, betaxolol, bisoprolol, methopropyl, seliprolol, carvediol, and labetolol. Nitrates include, for example, nitroglycerin.

The medicament for use in accordance with the invention may be administered, e.g., orally, parenterally, topically or rectally by any pharmaceutical preparation useful for said administration, and containing said medicament in pharmaceutically acceptable amounts, together with pharmaceutically acceptable carriers, excipients or vehicles known in the art. with. The preparation of such pharmaceutical preparations is well known in the art.

I <t • · »! . Thus, the pharmaceutical preparation may be in a dosage form suitable for oral administration, such as, for example, tablets, capsules, liquid dosage forms. ·,; suspensions, emulsions, syrups, etc. All such preparations are formulated using known formulation techniques and carriers. * '\ substances and additives. The drugs may also be administered parenterally, for example as aqueous or oily suspensions, emulsions, or dispersions containing; ''; active ingredient in combination with conventional pharmaceutically acceptable additives:. The rectally administrable dosage form may be, for example, in the form of suppositories containing the active prodrug in a carrier suitable for rectal administration. with the substance.

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. According to the invention, the medicament may also be administered topically for which ointments, creams, gels, solutions, suspensions, or the like, or any other transdermal delivery system or system are useful. Such dosage forms typically contain a pharmacologically active amount of said drug in association with a pharmaceutically acceptable carrier or vehicle known per se.

Thus, the therapeutic dose for the patient in need of treatment will vary with the weight and age of the patient and also with the condition being treated and the route of administration, and will be readily determined by one of ordinary skill in the art according to clinical practice.

Generally, a concentration of 0.01% to 5% of the active ingredient in a suitable carrier is / is suitable for topical application, while the dosage form for oral administration suitable for most purposes would be 0.1mg to 5g administered at 2-3 doses / day, typically in a unit dose of 0.1 mg to 500 mg.

Methods and results

Four subsequent studies were conducted to confirm the association between clinical vascular disease due to atherosclerosis and back pain, ie, spinal cord disease and osteoarthritis in middle-aged men.

Study 1: Vascular Diseases Related to Arteriosclerosis and Lower Back Disease ... The study material consisted of a population-based sample of 2682 men of Eastern Finland, aged between 42 and 60, who participated in Kuopio • _. ·. : Baseline for Ischemic Heart Disease Risk Factor Study (KIHD) • 2. . : stage from 1984 to 1989. The research population consisted of 2657 men,. · · ·. who had complete information on atherosclerotic vascular disease; including ischemic heart disease (IHD), stroke, and stroke »·» (claudication), and baseline data on lower back disease. Ongoing ; '·'; ischemic heart disease was defined by self-reported acute coronary artery disease: a history of, or chest pain, stress chest pain, or. ·. if nitroglycerin tablets were used at least once a week. The prevalent paralysis .... was defined by self-reported paralysis or Finmonica paralysis *. blades. The prevalent anthrax was defined by a self-reported interruption! ''. based on a pedestrian history. Statistical relationships between atherosclerotic vesicular disease and lumbar spine disease were analyzed using a logistic regression model.

Men with any form of atherosclerotic vascular disease had a 45% higher age-standardized risk of lower back problems than other men. The excess risk was reduced by 20% after adjusting for socioeconomic status in adults (OR 1.36.95% CI 1.14-1.63, p <0.001). Of all atherosclerotic vascular diseases, the main link with lower back disease was staple disease. Men with a history of claudication had a 86% (95% CI 25% -177%, p = 0.002) higher risk of developing lower back disease than other men. Extra risk was also maintained after adjusting for adult socioeconomic status (OR 1.76, 95% CI 1.18 - 2.61, p = 0.006). Men with ischemic heart disease had a 40% (95% CI, 17% to 67%, p <0.001) greater age-adjusted risk of lower back disease than other men. After adjusting for socioeconomic status in adulthood, the additional risk of lower back disease remained (OR 1.31, 95% CI 1.09-1.57, p = 0.004). 736 men with any history of atherosclerotic vascular disease had a 34% (95% CI 19% - 53%, p = 0.001) lower age-adjusted risk for lower back disease if they were regularly taking anginapectic-ris medication than non-prescribers . Regular users of beta-blockers had a 48% (95% CI 29% - 61%, p <0.001) lower age-adjusted risk of lower back pain than non-drug users.

. ,: The course of simple or non-specific lower back disease is typically reversible. ·. : and chronic and does not correlate with structural or degenerative changes (2).

. ' · Current treatment practice is largely inappropriate for simple lower back pain (1). The best treatment results are obtained when the patient resumes usual activities (4, 5).

: "': For the first time, we have shown that low back disease is clearly associated with clinical," ·. Detectable atherosclerotic disease in a population-based study.

.,.,: This confirms that general atherosclerosis, which causes hypoxia and tissue dysfunction, especially during exercise, and triggers pain-producing nociceptive '! ". Nerve fibers can cause lower back pain. In this study, more than any other patient who had had vascular disease and ischemic heart disease, 6,11503? was also a lower back disease. For men who had no detectable heart disease, atherosclerosis may nevertheless be a contributing factor to the development of lower back disease, since the first time that lower back disease has been found has been predicted to be fatal. that drugs that improve blood circulation and increase peripheral perfusion reduce the risk of lower back disease.

Study 2: Ischemic Heart Disease and Occurrence of Lower Back Disease / The purpose of this study was to test the hypothesis that ischemic heart disease, the most common clinical manifestation of atherosclerosis, is associated with an increased incidence of lower back disorders in middle-aged men. The subjects consisted of a population-based sample of 1,038 42-60-year-old Eastern Finnish men who participated in a four-year follow-up study as part of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). Baseline studies were conducted from 1987 to 1989 and four-year follow-up studies from 1991 to 1993. This study consists of 520 men with complete knowledge of ischemic heart disease and lower back disease who did not report lower back pain in the baseline situation. Predominant ischemic heart disease was defined by self-reported acute coronary artery disease or chest pain, chest pain, or need for nitroglycerin tablets at least once a week, or! . if the stress test should have been interrupted by chest pain or ischemic electrocardiographic findings in the stress test. Statistical connections to the prevailing is-. ·, · For the chemical incidence of heart disease and lower back disease were analyzed, · · -, using a logistic regression model.

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Men with ischemic heart disease had a 2.26-fold (95% CI 1.21 -; V. 4.24, p = 0.01) age-adjusted incidence of lower back disease compared to men without '': ischemic heart disease. after adjustment for socioeconomic status: · after reduction of additional risk by 15% (relative risk 2.06, 95% CI 1.09 -; 3.91, p = 0.03) Self-reported chest pain, interruption of stress test due to rhinitis, and ischemic electrocardiographic findings were directly related to the occurrence of lower back disease.

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Study 3: Atherosclerotic vascular disease and osteoarthritis

The subjects consisted of a population-based sample of 2,682 eastern Finns aged 42-60 who participated in the Baselme Survey of Kuopio's Ischemic Heart Disease Risk Factor Study (1984-1989). The study consists of 2,663 men with complete knowledge of atherosclerotic vascular disease, including ischemic heart disease, stroke and stroke, and osteoarthritis at baseline. Predominant ischemic / cardiac disease was defined by self-reported acute anamnestic chest pain or the need for chest pain, exertional chest pain, or at least weekly nitroglycerin tablets. The prevalent stroke was defined by a self-reported history of stroke or by the Finmonica stroke registry. The dominant claudication was defined by self-reported claudication history. Statistical relationships between atherosclerotic vascular disease and osteoarthritis were analyzed using a logistic regression model.

Men with any vascular disease associated with atherosclerosis had a 39% (95% CI 13-72%, p 0.002) greater age-adjusted risk of osteoarthritis than other men. Men with a history of claudication had a 58% (95% 0-3-142%, p = 0.03) higher risk and men with ischemic heart disease, .40% (95% CI 13-73%, p = 0.002) higher age-adjusted risk of osteoarthritis! . than other men. 739 with a man who had any atherosclerotic! history of vascular disease and who regularly used beta-blockers was, ·,; 25% (95% CI -6 to 47%, p = 0.103) lower age-adjusted risk of osteoarthritis, · · *. than those who did not use the medicine.

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Study 4: Spinal Microcirculatory I »II« ": Spinal blood flow and perfusion were measured using an optical laser Doppler · · flow measurement based on light scattering from moving blood cells and frequency offset according to the Doppler principle. - Flux laser Doppler, model PF 4001-1 (Perimed, Järfalla, Sweden) (6) Intravenous optical fiber was injected into the multifidus spinal cord by intravenous duct taper cannula Five patients with 8 and 4 with 11 low back disorders In the lower back pain patients, the blood flow to the spinal muscles was impaired, In the lower back pain patients, perfusion was reduced (flow rate multiplied by mean particle density) and pulse pressure was reduced compared to pain-free controls. to a low level instead of returning to an earlier level. One or more of these changes normalized after administration of sublingual nitroglycerin.

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Because clinical vascular disease is associated with lower back disease, it appears that the most important treatment strategy is to maintain and increase blood supply and tissue perfusion of the spinal structures, and to prevent oxygen deficiency, ischemic nerve irritation and nonspecific low back pain.

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REFERENCES

1. Bigos S, Bowyer O, Braen G, et al. Acute Low Back Problems in Adults. Clinical Practice Guideline No. 14, AHCPR Publication No. 95-0642. Rockville MD: Agency for Health Care Policy and Research, Public Health Service, US Dept. of Health and Human Services, 1994 2. Jensen M C, Brant-Zawadzki M N, Obuchowski N, Modic M T, Malkasian D, /

Ross J S: Magnetic resonance Imaging of the lumbar spine in people without back pain. N Engl J Med 331 (2): 69-73, 1994.

3. Penttinen J. Back pain and risk of fatal ischemic heart disease: 13 years follow up of Finnish farmers. BMJ 1994; 309: 1267-8.

4. Deyo R, Diehl A, Rosenthal M: How many days of bed rest for acute low back pain? A randomized clinical trial. N Engl J Med 315: 1064-1070, 1986.

5. Malmivaara A, Häkkinen U, Aro T, Heinrichs ML, Koskenniemi L, Kuosma E, Lapland S, Paloheimo R, Servo C, Vaaranen V and Hemberg S: Treatment of acute low back pain - bed rest, exercises, or ordinary activity? New Engl J Med 6: 351-355,1995.

• *> * ί! ! 6. Nilsson GE, Tenland T, Öberg PÄ: A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy. IEEE Trans Biomed Eng • 4 f 27: 12-19,1980.

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Claims (2)

11c05? Use of a beta-blocker or a nitrate for the preparation of a pharmaceutical composition for treating and / or preventing non-specific spinal disease, osteoarthritis and other degenerative musculoskeletal diseases. 1. Beta-salpaajan tai nitrraatin käyttö pharmaceuticals koostumuksen valmistamiseksi epäspecifisen selkäsairauden, nivelrikon ja muiden degeneratii-vist tuki-ja liikuntaelinsairauksien hoitamiseksi ja / tai ennaltaehkäisemiseksi. 2. Patenttivaatimuksen 1 mukainen käyttö pharmaceuticals koostumuksen valmistamiseksi paikallista käyttöä varten. Patentkav Use according to claim 1 for the preparation of a pharmaceutical composition for local use.