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Григорьева Л.В. Методы рациональной фармакотерапии болевого синдрома при нарушениях опорно-двигательного аппарата в практике семейного врача
25.07.2014, 00:20

Резюме
Григорьева Л.В. Методы рациональной фармакотерапии болевого синдрома при нарушениях опорно-двигательного аппарата в практике семейного врача.
В обзоре литературы проведено обобщение и анализ подходов рациональной фармакотерапии болевого синдрома при различных нарушениях опорно-двигательного аппарата, определены перспективные пути повышения экономичности и эффективности лечения в общей практике – семейной медицине. По результатам рандомизированных, контролируемых исследований показана эффективность проведения анальгетической и противовоспалительной фармакотерапии болевого синдрома при одновременном использовании комбинаций препаратов разных фармакодинамических групп. Длительная терапия НПВП может оказывать ульцерогенное действие на слизистую оболочку желудка и 12-ти перстной кишки. Способность НПВП ингибировать активность ЦОГ-1 ассоциирована с риском развития гастроинтестинальных осложнений. Вероятность их развития возрастает при перенесенной язвенной болезни желудка, одновременном назначении ацетилсалициловой кислоты, непрямых антикоагулянтов, глюкокортикоидов.
Селективные ингибиторы ЦОГ-2 оказывают минимальное повреждающее воздействие на слизистую желудка и менее значимое ульцерогенное действие. При длительном их применении повышается риск развития тромбоза венечных артерий, в особенности у пациентов с имеющимися факторами сердечно-сосудистого риска.
Ключевые слова: боль в спине, шее, остеоартроз, спондилоартрит, психогенные боли, подходы к лечению пациентов, принципы рациональной фармакотерапии, общая практика – семейная медицина.

Резюме
Григор’єва Л.В. Методи раціональної фармакотерапії больового синдрому при порушеннях опорно-рухового апарату в практиці сімейного лікаря.
В огляді літератури проведено узагальнення та аналіз підходів раціональної фармакотерапії больового синдрому при різних порушеннях опорно-рухового апарату, визначено перспективні шляхи підвищення економічності та ефективності лікування у загальній практиці - сімейній медицині. За результатами рандомізованих, контрольованих досліджень показано ефективність проведення анальгетичної та протизапальної фармакотерапії больового синдрому при одночасному використанні комбінацій препаратів різних фармакодинамічних груп. Тривала терапія НПЗП може надавати ульцерогенну дію на слизову оболонку шлунка і 12-ти палої кишки. Здатність НПЗП інгібувати активність ЦОГ-1 асоційована з ризиком розвитку гастроінтестинальних ускладнень. Ймовірність їхнього розвитку зростає при перенесеної виразкової хвороби шлунка, одночасному призначенні ацетилсаліцилової кислоти, непрямих антикоагулянтів, глюкокортикоїдів.
Селективні інгібітори ЦОГ-2 надають мінімальну шкідливу дію на слизову шлунка і менш значиму ульцерогенну дію. При тривалому їх застосуванні підвищується ризик розвитку тромбозу вінцевих артерій, особливо у пацієнтів з наявними факторами серцево-судинного ризику.
Ключові слова: біль у спині, шиї, остеоартроз, спондилоартрит, психогенні болі, підходи до лікування пацієнтів, принципи раціональної фармакотерапії, загальна практика - сімейна медицина.

Summary
Grigorieva L.V. Methods of rational pharmacotherapy of pain syndrome at locomotorium violations in the family doctor practice.
In a literature review the generalization and analysis of the approaches of rational pharmacotherapy of pain in various disorders of locomotorium have been carried out; the perspective ways to improve the efficiency and effectiveness of treatment in general practice - family medicine - have been defined. According to the results of randomized, controlled studies the effectiveness of analgetic and anti-inflammatory pharmacotherapy of pain while using different simultaneous combinations of drugs pharmacodynamic groups have been shown. The long-term NSAIDs therapy may have an ulcerogenic effect on the mucous membrane of the stomach and 12 duodenum ulcer. The ability of NSAIDs to inhibit the activity of COX-1 is associated with the risk of gastrointestinal complications. The probability of their development increases if the patient had a gastric ulcer with simultaneous administration of Acidum acetylsalicylicum indirect anticoagulants, glucocorticoids.
Selective COX-2 inhibitors make a minimum damaging influence on the mucous of the stomach and less significant ulcerogenic action. After prolonged use the risk of developing coronary artery thrombosis, especially in patients with existing factors of cardiovascular risk, increases.
Key words: dorsodynia, pain in the neck, osteoarthrosis, spondyloarthritis, psychogenic pain, approaches to treatment of patients, principles of rational pharmacotherapy, general practice - family medicine.

Рецензент: д.фарм.н., проф. Б.А. Самура

УДК 616.7-071.4-085:614.253.2

 Харьковский национальный университет имени В.Н. Каразина

 V. N. Karazin Kharkiv National University

doctor-exclusive@mail.ua

Pain is a spontaneous subjective sensation which appears because of incoming pathology impulses in the central nervous system from peripheral receptors of somatic nervous endings. After initial examination the cause of pain in 50 % of patients is still unclear and the frequency of the negative results in diacrisis makes up 60 % [4].

The pain syndrome in spine is the most common case which is associated  with the pathology in a musculoskeletal system. It is known that  backbone pain takes the 5th place among all reasons of visits to a doctor and the 2nd place among the reasons of disablement .

About 25 % of loss of working hours is connected with them. The fact that the significant prevalence of back pain has a fairly  young age (from 30 to 50) is of utmost importance [17].

Pain syndromes in a back is one of the main reasons for an outpatient health encounter including the visits to family doctors [1, 11]. Up to 90 % of adults face with the back pain and at least once a year they suffer from the exacerbation of pain. Frequent form of pain is pain in the lower back [4].

In most cases the source of pain is a degenerative dystrophic change of large and small joints of the backbone. In some cases the cause of pain syndrome is osteochondrosis [35].

The incidence of osteoarthritis (OA) has tripled among men and nearly doubled among women [34]. Generally about 9.6 % of men and 18 % of women over 60 have symptomatic OA [50]. In other studies the existence of pain in the knee joints associated with OA is 25–37 %. The frequency of diseases increases with age and also in the presence of obesity or traumas [7, 12].

The pain syndromes in an axial skeleton arise periodically in almost all people over the age of 40 years. This is one of the most frequent reasons of temporary incapacitation.  Degenerative diseases of the spine main pathogenetic factors in the development of these syndromes are the compression mechanisms and reflex effects with concomitant inflammatory disorders of microcirculation disorders and their combinations [33]. The peculiarity of pain syndromes of the lumbar spine is a combination of reflexive muscle-tonic and myofascial syndromes with changes in the emotional and personal sphere [25, 36].

The basic clinical implications of most inflammatory and degenerative diseases of the spine and joints are pain, muscular spasm, stiffness and limited mobility [26, 59]. All these implications are closely connected and actively interact with each other. Pain and stiffness are most characteristic of rheumatoid arthritis, joints and spine leisons, in inflammatory bowel diseases (heterospecific ulcerative colitis), undifferentiated spondylarthritis. The same implications are inherent in many other diseases [43, 60].

The intervertebral disk disease which induced the constriction injury of the spinal roots can be the reason of discogenic radiculopathy [9, 61]. Also the cause of pain syndrome can be the hypertrophied spinal ligaments and vertebral fractures  due to osteoporosis [8, 54].

The presence of inflammatory process in an axial skeleton can be the  cause  of reflex tension of spine muscles , then pains appears, which in turn leads to the change in posture and promotes deformation of the spine [28].

Persistent tonic tension of back muscles, torso is a natural reaction of the body to  emerge pain. The reaction of muscular tension on the first stage has a vicarious in nature and continuing for a long time, it supports pain [5, 53]. Spastic muscles is the secondary source of pain and trigger a vicious cycle which brings to the development of myofascial syndrome [28]. The spasticity is understood as a movement disorder accompanied by increasing myotonus. It is caused by the defeat of corticospinal way [46].  Spasticity syndrome is the manifastation of the upper motor  neuron  excitability. The regulation of myotonus is influenced by the central and peripheral impulses of α-spinal motoneurons. These somatic motoneurons are located in the anterior horns of spinal cord. They effect the innervation of muscular fibres [23].  To defeat these varied symptoms of motor neurons,in addition to rigidity of muscles,  muscle myatrophy and development of contractures are included. A significant role in the transformation of acute pain into a chronic one, play, among other reasons, violations in emotional sphere [8, 10]. In the presence of many rheumatic diseases the syndrome of spasticity is also formed, but its intensity is less expressed.

The predisposing causes of pain are overweight, a frigorism, physical activities inappropriated to the state of health, a longterm stay in a forced position, wrong organization of a workplace [45].

Among the existing variety of pain syndromes the presence of psychogenic pain with localization in the lower back should be also noted. For such variant of pain anxiety and depressive disorders, mildly expressed musculotonic syndrome,  pain in the lowerback  axial load, the disparity of sensory disorders in the zone of a nerve-root innervation have been typical [51, 53].

At the present two basic forms of pain are usually distinguished: sharp and chronic. Sharp pain is diagnosed in about 80 % of the cases. Sharp pain arises as a result of tissular damage; it proceeds for less than 3 months and terminated well by analgetics. Chronic pain proceeds for more than 3 months and is not terminated by analgesics [42, 44].

The development of chronic pain syndrome, its severity, time duration and efficiency of the therapy are also defined by the emotional state of a patient, the presence of anxiety and depressive disorders. The 21st century is characterized by the intensive growth in the number of office workers. They have musculoskeletal pain in the neck, the infrascapular area, the lower back. Prolonged sitting position increases pressure on the front disk of the spine, spraining of its back side, poor hydration, blood supply to the disk, disruption of muscle tone back and abdominals [24, 32].

Today arthral-muscular pain syndromes localized in the back present the most widespread clinical problem [22, 31].

The target of the pharmacotherapy of patients with musculoskeletal syndrome is simultaneous elimination of pain, muscle spasm and renewal of functional activity of the patient [55].

The nervous endings that perform the function of nociceptors are found in the capsules of intervertebral joints, in the dorsum of longitudinal and interspinous ligaments, periosteum of vertebrae, in the walls of arterioles and veins and vessels of juxtaspinal muscles, the outer third of the fibrotic ring of intervertebral disks [46].

The impulses from receptors reach the motor neurons of spinal cord which results in increased tone of appropriate muscles. The constricted muscles promote the limitation of mobility of a certain segment of the spine and also become the secondary source of pain [38].

At present nonsteroid antiinflammatory drugs (NSAIDs) [37] are most widely applied to the pain relief. Anodynia is not a guarantee of preventing the conversion of sharp pain to the chronic one and neither prevents the subsequent exacerbations. Application of NSAIDs is more efficient for pain relief [2].

The basis of their pharmacological action is the ability to inhibit the activity of cyclooxygenase (COX) which is a key enzyme in the metabolism of arachidonic acid. Reduction of prostaglandin synthesis leads to the decrease of synthesis of inflammatory mediators; the sensitivity of the nerve structures to bradykinin, histamine, nitrogen oxides, which isformed in the tissues during inflammation, reduces [15].

The ability of NSAIDs to inhibit COX activity is associated with the risk of gastrointestinalny complications [49]. The probability of their development increases with the transferred stomach ulcer, simultaneous prescription of acidum acetylsalicylicum, indirect anticoagulants and glucocorticoids (GC) [13].

Selective COX-2 inhibitors make minimal damaging effect on the gastric mucous and less significant ulcerogenic action [4, 16]. With the long-term use of NSAIDs the risk of coronal artery thrombosis increases, particularly in patients with existing factors of cardiovascular risk. Patients with a skeletal and muscle pain syndrome have no need for a long-term NSAIDs treatment. The term of their use should not exceed the time sufficient for elimination of pain [3, 14].

In the treatment of patients with sharp and chronic pain it is necessary to consider the role of a muscle spasm in the emergence and maintenance; neuromuscular blocker is to apply then. Modern medicinal preparation Katadolon (Flupirtine maleate) at the same time eliminates muscle spasm and pain [40, 56].

The numerous research conducted in countries of Western Europe, the USA have allowed to establish a high analgetic efficiency of the medicinal product and its ability to remove muscle spasm with good toleraability. Myorelaxation effect of Katadolon is realized due to indirect antagonism of NMDA receptors and owing to interaction with GABA-ergic systems, it decreases Са2 + intracellular concentration and, also prevents acute pain transformation into the chronic one [6, 20]. Myorelaxing effect of the drug is associated with the blockage of excitation transfer in the intercalary and motor neurons. In this regard, the normalization of the raised muscle tone occurs only in the area of pain without causing a decrease in muscle strength [13].

Katadolon strengthens the effects of alcohol, sedatives and relaxants. When it is administered concurrently with coumarin derivatives, the monitoring of prothrombin index is recommended [19]. It is necessary to avoid the combined use of Katadolon and medicines containing Paracetamolum. However, the medicine’s acceptability is good and it is completely safe. With the long-term application of Katadolon the anesthetizing effect not only does not decrease, but in some cases becomes more expressed [10].

The basic principles of the treatment of pain in spine is an exception of unfavorable staticodynamic loads, inducing column muscles activity, the intervention to vertebral and extravertebral damaged centers, the administration of NSAIDs and the gentle nature of medical treatment [57].

Pharmacotherapy of the above variations of pain syndromes is directed to the pain relief by nonnarcotic analgetics and, also, administrating of antiepileptic and counterdepressant agents, conducting the anti-inflammatory therapy (NSAIDs, glucocorticoids), intaking neuromuscular blockers and anticholinesterase agents [15].

In December 2011, in Germany a prospective, randomized, double blind, placebo- and active-controlled study of the efficiency and safety of Flupirtine sustained release was completed [47]. The character of the new form of long acting tablets – Katadolon forte (400 mg) is the mechanism of an active ingredient release: 100 mg are released within 2−3 hours after medication intake, providing fast anesthetic effect on the patients with  dorsodynia, 300 mg − for a period of 1 day providing longanesthetc effect [21].

The high efficiency and good acceptability of the medicine, as well as the convenience of single-use during a day, are established. While there is a steady analgesic effect. The data obtained allow us to recommend Katadolon and Katadolon forte as the agents of choice for patients with dorsodynias, as well as the syndrome of an office worker [20, 24].

Elderly people with clinical signs of OA need meticulous examination, because they have a multiple accompanying pathology (hypertension and coronary heart disease, diabetes mellitus of the 2nd type, obesity, etc.). Approximately 60 % of patients with OA of major joints indicated the existence of other chronic diseases. The risk of side effects caused by uncontrollable intaking of nonnarcotic analgetics including NSAIDs, increases [44].

 

The use of Paracetamolum in treatment of OA of the knee and hip joints is presented in such recommendations as EULAR, and OARSI [62]. The recommended daily dose can make no more than 4 g/day. According to prospective randomized research the use of Paracetamolum during 12 weeks led to a decrease of pain syndrome on WOMAC scale in 44 % of cases, while in the placebo group – in 39% of cases. Improvement functions on Paracetamolum therapy in comparison to placebo was not statistically reliable. According to the comparative study of Paracetamolum and NSAIDs (maximal doses) the pain syndrome with Paracetamolum use for 9 weeks on ascale of WOMAC decreased in 38 % of patients, while when NSAIDs was used – in 48 %. Improvement of function in the joint during therapy with Paracetamolum within 9 weeks was observed in 38 %, against NSAIDs reception – in 48 % [2].

The possibilities of peroral NSAIDs (including COX-2 inhibitors) and NSAIDs of local action are also described in recommendations of EULAR and OARSI for the treatment of OA of the knee and hip joints [62].

It should be noted that Aceclofenac is the highly effective NSAIDs which expression of anti-inflammatory efficiency is as good as Indomethacinum and Diclofenac and it is well tolerated. Aceclofenac can be successfully used for the long-term use in patients with an ankylosing spondylitis (AS) and other spondylarthrites (SpA), both in the treatment of joint inflammation and in managing and preventing the relapse [29, 48].

Several authors conducted research in which 104 patients with AS for 3 months compared Aceclofenac toleraability in a dose of 100 mg 2 times/day and Naproxenum in a dose of 500 mg 2 times/day. The patients who took Aceclofenac (25 %) had the total number of the side effects less than the patients treated with Naproxenum (33 %). Disorders of the gastrointestinal tract (including abdominal pain, nausea, heartburn, diarrhea) were observed in 18 % of patients in the Aceclofenac group and in 21 % of patients in the group with Naproxenum; 1,6 and 6 % of patients respectively were compelled to interrupt the treatment. The general assessment of drug acceptability both by the patient and the doctor was in favor of Aceclofenac [17, 39].

In a multicenter double blind, randomized research 235 patients with AS took Aceclofenac 100 mg 2 times/day or Tenoxicam 20 mg/day for 3 months. Patients in both groups significantly reduced morning restraint and pain the indexes of a Chober test and lateral bending of the spine, its mobility improved  , thorax excursion increased. No significant distinctions in the treatment effectiveness between the two groups were not revealed [29].

Selection of NSAIDs in each case is individual, however the necessity of the long-term intake dictates the searchof the drug that combines a distinct antiinflammatory effect with good toleraability. One of such preparations is a derivative of a-toluic acid Aceclofenac (Aertal). Aceclofenac is available in tablets of 100 mg [17, 41].

Side-effects in patients treated with Aceclofenac were less common than in the treatment of Indomethacinum, Naproxenum, Diclofenac, which is confirmed by a number of comparative research. So, from 310 patients with AS who took Aceclofenac 100 mg 2 times/day or Indomethacinum 100 mg/day, the side effects were noted in 30,3 % in Aceclofenac group and in 46,6 % – in the group of indometacin [15]. No significant differences with regarding to gastrointestinal complications (1,3 % of cases at treatment of Aceclofenacy and 3,26 % in the treatment with Indomethacinum) and hemopoiesis violations (1,9 % and 5,9 % respectively) between the two groups were revealed. At the same time, the frequency of neurologic disorders (mainly headache and dizziness) was significantly lower in a group of the patients who intook Aceclofenac (2,6 % against 13,7 %; р<0,001).

The spectrum of adverse events in the treatment of Aceclofenac was closely similar to that of other NSAIDs treatment, however, significantly differed in frequency of their development. This has been demonstrated in a study SAMM (Safety Assessment of Marketed Medicines), which was participated by 10 142 patients (7890 patients were appointed Aceclofenac, 2252 patients - Diclofenac), suffering from RA, osteoarthritis and AU [29, 50]. The results of the research testified to the best profile of Aceclofenac acceptability in comparison to Diclofenac. The authors formulated a conclusion that the application of Aceclofenac was accompanied by less risk of NSAIDs-gastropathies and better acceptability. It is important to take into account that among the patients receiving Aceclofenac there were much more patients with pathology of gastrointestinal path in the anamnesis [39].

The pharmacokinetic profile of the drug practically does not differ from a single dose and repeated intaking, as well as in different age groups. Patients with liver failure marked a slowdown in the pharmakokinetics of Aceclofenac. In this connection these patients are recommended to intake half the standard dose. No significant changes in the pharmakokinetics of the drug in moderate renal sufficiency was revealed. But because Aceclofenac is excreted mainly by kidneys, in this case, careful monitoring of their function is recommended. Aceclofenac penetrates into synovial fluid, where its concentration makes 50 % of plasma. Aceclofenac proved itself as a highly effective drug against various forms of SpA. Its influence on pain expression, morning restraint, spinal mobility has been marked [57].

The therapeutic efficiency of Aceclofenac was compared with placebo or other NSAIDs in a number of studies in various rheumatic diseases, including AS. In the 12-week comparative study of Aceclofenac and Indometacin 310 patients with AS were randomized to take Aceclofenac 200 mg/day or Indomethacin 100 mg/day. Patients of both groups considerably improved all clinical parameters (pain, morning stiffness, lateral bending of a backbone) and the general condition. It was assessed by the doctor and the patient in comparison with the initial. No significant distinctions between the two groups were revealed. Good and excellent results in pain were observed in 52 % of patients treated Aceclofenac, and 64 % of patients treated Indomethacinum. Morning restraint decreased 70 % in Aceclofenac group and 68 % – in the group of Indomethacinum [39].

Many patients with OA do not receive adequate medical care. The research conducted in Great Britain showed that only 33 % of patients are older than 50 years who feel pain in the knee joints for 1 year or more, visited a general practitioner. Other patients are self-medicated. The basic reason for a timely visit to the doctor was pain in joints, with the absence of other significant deviations in  health status, and also expressed intensive character of pain caused by the development of functional violations of the organism [19].

According to EULAR and OARSI recommendations peroral NSAIDs have to be used in the treatment of OA of the knee and hip joints in the case of an inefficiency of Paracetamolum. In patients with the increased gastrointestinal risk (including those with the anamnesis of peptic ulcer or bleeding from the upper departments of the gastrointestinal path, but not within the last year) the usage of non-selective NSAIDs only in combination with gastroprotektor (inhibitors of a proton pomp) or selective inhibitors of COX-2, is acceptable. It is necessary to seek for the application of a minimum efficient dose of NSAIDs in OA treatment. Both selective and non-selective NSAIDs have to be used with caution at high cardiovascular risk [62].

The intra joint introductions of GC, according to EULAR, are recommended for the therapy of OA of the knee and hip joints of heavy and average degree. In the case of knee OA the greatest effect is the combination of intra joint injections with preliminary evacuation of intra joint liquid. According to OARSI recommendations, intra joint injections of the group companies should be used in patients who do not respond to the therapy with analgetics or NSAIDs with the presence of signs of synovitis or local inflammation [64].

Modern principles of complex treatment include the use of modifying drugs in slow action, which contain chondroitin sulfate. All 3 major professional organizations (EULAR, OARSI and ACR) agreed in the opinion that chondroitin sulfate has a long-term history of application. The results of laboratory and clinical research testify the presence of chondroitin sulfate in symptomatic properties and, and most importantly, about the possible structure- modifying effects of the medicine [27, 64].

The medicine has ntiinflammatory and analgesic properties, promotes decreasing emission in the synovial fluid of mediators of inflammation and pain through synovioretseptory factors and macrophages of the synovial wall, suppresses the secretion of leukotriene B4 and prostaglandin E2 [63].

At present, the therapy of OA uses various medicinal forms of chondroitin sulfate. The widespread application was found to Artradol that contains lyophilized powder of chondroitin sulfate to preparethe solution for intramuscular injections. The drug is made from high-quality raw materials with using modern technologies [29, 32].

Artradol is easily absorbed when injected intramuscular and in 30 min it is found in considerable concentration in the blood, and in synovial fluid - in 15 min. The maximum concentration is achieved in 1 hour after the injection. Then the concentration of the drug slowly decreases within 2 days. The medicine is accumulated mainly in cartilaginous tissue (maximum concentration in the joint cartilage is achieved in 48 h) [30, 52].

Therapy of miofastsial pain syndrome (MPS) is aimed at relaxation of the muscles involved in pathological process and removal of pain [29, 39]. The most widely accepted method of therapy is the using of relaxants, NSAIDs and analgetics: Baclofenum, Tolperisonum and Tizanidine are applied. For elimination of pain in the acute phase analgetics and NSAIDs are administrated. Nonsteroid analgetic drugs are successfully taken for pain relief with MBS because of combination of analgetic and antiinflammatory characteristics [30, 54].

Ketoprofen and its analogue Flamax is one of widely used NSAIDs. The medicine has analgesic, anti-inflammatory and antipyretic effect. Flamax mechanism of action, as well as other not-selective NSAIDs, is associated with depressive activity of cyclooxygenase (COX-1 and COX-2). COX is the main enzyme of  metabolism of the arachidonic acid, a precoursor of prostaglandins, which take the central place in inflammation and pain pathogenesis. Flamax is used to relieve sharp pain. It is produced in the solution form for intravenous and intramuscular injectios. Intravenous infusional administration of the drug is carried out only in a hospital. Flamax can be combined with analgetics of the central action, it can be mixed with Morphinum in one. You cannot mix it in a bottle with Tramadol because of the possibility of precipitation. The long-term intake of NSAIDs in efficient doses can lead to adverse undesirable phenomena in the gastrointestinal path, kidneys, hemopoietic system [52].

Most effective are invasive methods of influence as they hold blockades in trigger points. Injections can contain analgetic (novocainic blockade), NSAIDs, corticosteroids [14].

Long-term recurrent pain syndromes are stopped by antidepressants (Amitriptyline, Venlafaxine, Duloxetine). Antidepressants possess characteristic analgetic effect. The therapeutic effect of this group of drugs is developed within 1–2 weeks. To achieve the lasting clinical effect it requires a long-term taking for at least 3 months [2].

The main reasons of neck pain are grouped as follows: degenerative diseases of the spine, neck injury and pain reflected in internal diseases and psychogenic pain [13, 17]. Most common causes are osteochondrosis and osteoarthrosis of the spine cervical department. The prevalence of degenerative diseases of the backbone, osteochondrosis and osteoarthrosis increases with age [58].

Neck pain accompanied with febricula, chills, leukocytosis and other inflammation signs can be caused by infectious process. Examples include loss of bone tissulars in osteomyelitis and tuberculosis, inflammation of the lymph nodes −  lymphadenitis,  thyroid gland,  poliomyelitis, tetanus, shingles, meningitis, etc. [62].

A large number of studies on the therapy of a sharp and chronic pain syndrome in the neck testify of a good therapeutic effect of physiotherapy, chiropractic manipulations and therapeutic exercises [64].

Medicinal therapy of pain in the neck is usually combined. It includes NSAIDs, nonnarcotic analgetic relaxants which remove a muscle spasm (Baclofenum, Tizanidine, Tolperisonum, botulinum toxin), tricyclic antidepressants (amitriptyline), microcirculation stimulators (Pentoxifylline, Actovegin, niacin) and antioxidants (redoxon, vitamin E, thioctic acid, Mexidol) [17]. The main therapeutic effects of NSAIDs - analgetic, antiinflammatory and antipyretic - are based on reducing the synthesis of prostaglandins from arachidonic acid by means of COX enzyme inhibition [19].

Ketoprofen lysine salt inhibits COX-1 and COX-2, suppressing synthesis of prostaglandins. Ketoprofen lysine salt has anti-inflammatory, anesthetizing and antipyretic property. The guick onset of action is explained by the higher solubility of Ketoprofen lysine salt. High solubility promotes faster and complete absorption of the active ingredients, which achieves to the peak of blood plasma concentration after peroral reception in 15 min. [20, 57].

A variety of dosage forms of the drug extends the range of its application. Accepted by mouth or injected rectal the lysine Ketoprofen salt has systemic anti-inflammatory and analgesic effect and is used for the therapy of various inflammatory processes which occur with sharp pain. When prescribing the NSAIDs therapy special attention should be always paid to the side effects typical of this group of drugs, and first of all it concerns gastrointestinal and hemopoietic systems [21, 32].

The local form among NSAIDs  − Artrozilen spray (Ketoprofen lysine salt) - has a high efficiency concentration and allows to provide faster therapeutic effect. Sometimes the action comes just as quickly as in intravenous administration. In the pilot studies, it was shown that the analgetic and antiinflammatory effect of Artrozilen spray is stronger than Diclofenac gel. Artrozilen gel and spray do not cause irritation and xeroderma and have no side effects [2].

It is now established that the lumbar pain (LP) is caused by a number of degenerative processes in tissues of the backbone and the formation of LP is bound to excessive exercise stresses, continuous stay innon-physiologic position, repeated travmatization of the vertebrae and intervertebral disks, as well as some other reasons. The role of such factors matters for the development of LP both in adult and young age [8, 21]. The development of LP can be favoured by clinically significant anomalies of the spine formation − a considerable asymmetry of thelength of the legs, especially the development of pelvic bones, lumbalization or  sacralization of sacral and lumbar vertebrae, the concrescense of vertebrae and so forth [37].

The Pain syndromes (PS) caused by degenerative diseases of the column and located near weak tissulars are found in 70−90 % of the adult population [1, 27]. In  result the taken NSAIDs therapy the majority of patients have the pain stopped within 3−4 weeks, and 3/4 of  them come back to their previous labor activity [32].

The leading objective of treating the patient with PS is the relief of pain and creation of the conditions for the full-fledged course of rehabilitation. Duration of load restrictions has to be defined by the intensity of pain and non excess of the appropriate limits. The rigorous immobilization is expedient for 1−3 days. For the treatment of PS, NSAIDs are prescribed [15].

One of the COX inhibitors, that have larger affinity for COX-2, is Meloxicamum. The significant experience of Meloxicam application by patients with osteoarthrosis of various joints (knee, coxofemoral), pseudorheumatism, has been accumulated [59]. Effectiveness of Meloxicamum for the rekief of pain in patients with PS has been confirmed with the combination of dorsopatiya and radicular syndrome. Most of these studies were carried out in the form of those double-blind randomly monitored [45].

Generally, pain relief should be considered as an opportunity for expansion of the motive mode of the patient, together with medical gymnastics and the formation of the patient’s correct movement stereotype.

A number of researchers found that Meloxicamum in a dose of 7,5−15 mg is correlated with therapeutic dosages of Diclofenac (100 mg), Piroxicam (20 mg), Naproxenum (750 mg) and some other NSAIDs. Most of authors have noted good tolerability of the drug, emphasizing its applicability even in cases where the patient has an intolerance to drugs from NSAID group (in particular, allergic reactions of the integuments, mucous) [18]. Meloxicamum might be intaken by the patients who need continuous receiving of Acidum acetylsalicylicum as an antiagregant therapy. It is also important that Meloxicamum has a low incidence of ulcerogenic complications in comparison with the majority of NSAIDs [14].

The study of the efficiency and acceptability of Meloxicamum among children was done. 225patients at the age from 2 to 16 years suffering from arthritis took Meloxicamum in the form of oral suspension for 3−12 months. The therapeutic efficacy and the side effects were comparable to those of Naproxen [22].

Medicines improving microcirculation and promoting  normalization of  metabolism of nervous tissular are widely applied for the treatment of patients with PS. Vitamin B complex, activators of  tissular metabolism, the pharmaceuticals able to intensify energy balance are administrated for this purpose. Simultaneous combined application of vitamin B complex and NSAIDs allows to reduce the term relief of pain, it increases the effectiveness of analgetic therapy and can promote to increase the period of remission [26].

Duration of treatment of patients with PS is determined by the intensity and character of the existing pain, its severity and rates of the clinical effect approach . Taking of NSAIDs should be stopped as after the onset of the effect. The inexpediency of preventive application of NSAIDs for the patients not experiencing pain should be noted.

The cardinal direction in the treatment of patients with PS is a widely used application of non-drug methods. The effectiveness of a number of physiotherapeutic procedures has been confirmed. In particular, data on analgetic activity while applying therapeutic ultrasound have been received, the effectiveness of treatment has been increased by phonophoretic medication. Also, its sufficiently high potency was confirmed by various methods of massage techniques [63].

The application of manual massage in the sharp stage of a disease in the presence of intense pain is inexpedient. It is reasonable to begin the procedure when the sharp pain relieved. It is considered that the positive effect observed as a result of its use, lasts for several months. Along with the use of massage it is necessary to begin medical gymnastics. Application of various reflexotherapy techniques, such as, acupuncture, and acupressure − manual treatment of the reflexogenic zones, is also possible. However the effectiveness of this method demands clarification with the use of randomized clinical studies [32, 47].

An important direction of medical influence, which is included into complex therapy of patients with PS, are such methods as techniques of manual therapy,  post-isometric relaxation. It is proved that the effectiveness of this method of treatment increases if the treatment starts not later than 3 months from the moment of pain [51]. The likelihood of achieving a positive effect increases with simultaneous use of therapeutic gymnastics. Preventive measures and a complex therapy of chronic pain syndrome with the use of both drug and non-drug methods of action allow to improve the state of the patient’s health [15].

During the chronic pain syndrome the integrated psychophysiological approach that considers the value of both the peripheral and psychological factors in an origin of pain is needed. Cognitive psychotherapy has to include correction of patient’s vision about the pain nature, the explanation of the plan of medical actions and the importance of each of thebtherapy components, an explanation of the importance of the dosed physical activity to relieve pain, learning relaxation techniques [52].

The prevention of a musculo-tonic syndrome requires daily physical gymnastics, recommended swimming lessons, getting rid of excess weight, massage courses, proper organization of the work-rest ratio [63].

It is also important to estimate the body’s response to effect of medicines. Only the knowledge of the pharmacodynamics of various groups of drugs and characteristcs of pathogenesis of disorders of a locomotorium of a given patient can make a rational choice of drugs and optimize careful, efficient and safe pharmacotherapy of pain in a family doctor practice [3, 7, 18].

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