STUDY OF THE EFFECT OF A COMBINATION OF L-THYROXINE, DICLOFENAC SODIUM AND CHONDROITIN SULPHATE ON PAIN IN OSTEOARTHRITIS DUE TO HYPOTHYROIDISM

Nosivets D. S.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Abstract. The article investigates the effect of a combination of L-thyroxine, diclofenac sodium and chondroitin sulfate on pain in osteoarthritis due to hypothyroidism. Today, the study of comorbid pathology is gaining more and more attention in modern medicine. The urgency of this problem is due on the one hand to the prevalence of osteoarthritis and hypothyroidism, and on the other – their mutual aggravating effect, which leads to atypical clinical situations. In this comorbid pathological condition there is a need for simultaneous appointment of basic hormone replacement therapy of functional insufficiency of the thyroid gland with L-thyroxine and symptomatic treatment of osteoarthritis with NSAIDs and chondroprotectors. The experiments were carried out on 60 white outbred rats of both sexes, which recreated osteoarthritis and hypothyroidism. Experimental osteoarthritis was performed by single intra-articular administration of 0.1 ml of monoacetic acid solution in the knee joint, which was prepared at a rate of 3 mg of the reagent on 50 mkl of sterile physiological saline. Experimental hypothyroidism was reconstructed by enteral administration of a 0.02% solution of carbimazole, which was prepared at a rate of 5 mg per 250 ml of physiological solution and given with a drinking ration of animals for 6 weeks. The pain threshold was determined in rats by three methods – vocalization reaction for electrodermal irritation of the root of the tail, model of thermal irritation of the root of the tail and model of “acetic acid cramps” with a single injection of drugs (diclofenac sodium + chondroitin sulfate + L-thyroxine) 10 mg/kg, 35 mg/kg and 0.0015 mg/ kg, respectively, against the background of osteoarthritis and hypothyroidism. Diclofenac sodium and L-thyroxine were administered intragastrically, and chondroitin sulfate was administered intramuscularly. To perform the test of electrodermal irritation of the root of the tail, iron needle electrodes (0.5 mm in diameter) with a fixed distance between the electrodes (10 mm) were injected under the skin distal to 1 cm from the root of the rat’s tail. Pain sensitivity was assessed at 30, 60, 90, and 120 minutes after the onset of the vocal response (squeak/vocalization) in response to the gradually increasing electrical stimulation from the ESL-2 stimulator. When performing the model of thermal irritation of the root of the rat’s tail, hot water (t=60° С) was used as a pain factor. The constant temperature was maintained by a thermostat. Rats were fixed in a pencil case and calmed by stroking. Painful irritation was reproduced by immersing the tail in hot water at a temperature of 60° C. During the study, the reaction time (latency period) in seconds (pulling/pulling the tail out of the water) was calculated. The test of peritovisceral pain of acetic acid cramps is based on change of sensitivity of C-polymodal nociceptors of a serous cover of a peritoneum in the presence of algogen. The principle of the model is based on the fact that intraperitoneal administration of 0.6% acetic acid solution with a volume of 0.1 ml per 10 g of rat body weight. Statistical data processing was performed using the Statistica 6.1 software package (StatSoftInc., Serial number AGAR909E415822FA) and included calculations of arithmetic mean values (M) and their errors (± m). The probability of the difference between the arithmetic mean (p) values of the indices was made using non-parametric — U-criterion Mann-Whitney. The determination of the probability of intragroup and intergroup differences was performed using the parametric t-criterion of the Student and the method of single-factor dispersion analysis (ANOVA). Differences were considered statistically significant at p≤0.05. Based on the study, it was found that the combination of diclofenac sodium + chondroitin sulfate + L-thyroxine exhibits a more pronounced analgesic effect in the test, which reflects the suprasegmental level of analgesia – in the test of electrocutaneous irritation of the rat tail. Thus, 30 minutes after the administration of the combination, the pain threshold in animals decreased 1.7 times (p<0.05), and by 60 minutes it decreased 2.2 times (p<0.05). The combination of drugs exerted a factor of 1.73 (p <0.05) on the pain threshold during thermal stimulation of the tail in rats for 60 minutes (p <0.05), reaching a maximum 90 minutes after administration. With a single administration of sodium diclofenac + chondroitin sulfate + L-thyroxine, the likelihood of “writhing” in animals after administration of 0.6% acetic acid decreased by 7.7 times (p<0.05). The given combination – diclofenac sodium + chondroitin sulfate + L-thyroxine with a single administration has a pronounced analgesic effect, which can be used for pain against the background of a comorbid pathology of osteoarthritis and hypothyroidism.

pain, pain threshold, osteoarthritis, hypothyroidism, diclofenac sodium, chondroitin sulphate, Lthyroxine, pharmacotherapy.

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«Bulletin of problems biology and medicine» Issue 1 (159), 2021 year, 97-101 pages, index UDK 615.017:616.72-007.248-009.7-06:616.441-008.64

10.29254/2077-4214-2021-1-159-97-101