The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study
O efeito da cetamina S(+) intra-articular em baixas doses na osteoartrite em ratos: um estudo experimental
Eugênio dos Santos Neto, Pedro Paulo de Alcantara Pedro, Maria do Socorro de Sousa Cartágenes, José Osvaldo Barbosa Neto, João Batista Santos Garcia
Abstract
Background
This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model.
Methods
Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg−1). Behavioral and histopathological assessments were conducted up to day 28.
Results
S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation.
Conclusion
Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes.
Keywords
Resumo
Introdução
Este estudo teve como objetivo investigar o impacto analgésico da S(+)-cetamina no comportamento da dor e na inflamação sinovial em um modelo de osteoartrite (OA).
Métodos
Os animais foram agrupados da seguinte forma: OA-Salina (n = 24) e OA-Cetamina (n = 24), OA induzida via monoiodoacetato de sódio (MIA) intra-articular; um grupo sem OA (n = 24) serviu como controle. No 7º dia após a indução da OA, os animais receberam solução salina ou S(+)-cetamina (0,5 mg.kg−1). Avaliações comportamentais e histopatológicas foram realizadas até o dia 28.
Resultados
A S(+)-cetamina reduziu a alodinia do dia 7 ao 28 e a hiperalgesia do dia 10 ao 28. Aliviou notavelmente os déficits de distribuição de peso do dia 10 até o final do estudo. Melhora significativa na caminhada foi observada no dia 14 em ratos tratados com S(+)-cetamina. A partir do dia 14, os grupos com OA apresentaram declínio da força de preensão, que foi contrabalançado pela S(+)-cetamina no dia 21. No entanto, a S(+)-cetamina não diminuiu a inflamação sinovial.
Conclusão
Baixas doses intra-articulares (IA) de S(+)-cetamina reduziram a dor de OA induzida por MIA, mas não reverteram as alterações histopatológicas sinoviais.
Palavras-chave
References
1. Ahmed AS, Li J, Erlandsson-Harris H, Stark A, Bakalkin G, Ahmed M. Suppression of pain and joint destruction by inhibition of the proteasome system in experimental osteoarthritis. Pain. 2012;153:18−26.
2. Lorenz H, Richter W. Osteoarthritis: cellular and molecular changes in degenerating cartilage. Prog Histochem Cytochem. 2006;40:135−63.
3. Miller KE, Hoffman EM, Sutharshan M, Schechter R. Glutamate pharmacology and metabolism in peripheral primary afferents: physiological and pathophysiological mechanisms. Pharmacol Ther. 2011;130:283−309.
4. Medeiros P, Negrini-Ferrari SE, Palazzo E, Maione S, Ferreira SH, de Freitas RL, et al. N-methyl-D-aspartate Receptors in the Prelimbic Cortex are Critical for the Maintenance of Neuropathic Pain. Neurochem Res. 2019;44:2068−80.
5. Matta C, Juhasz T, Fodor J, Hajd u T, Katona E, Szucs-Somogyi C, et al. N-methyl-D-aspartate (NMDA) receptor expression and function is required for early chondrogenesis. Cell Commun Signal. 2019;17:166.
6. Richards MM, Maxwell JS, Weng L, Angelos MG, Golzarian J. Intra-articular treatment of knee osteoarthritis: from antiinflammatories to products of regenerative medicine. The Physician and sportsmedicine. 2016;44:101−8.
7. Shetty YC, Patil AE, Jalgaonkar SV, Rege NN, Salgaonkar S, Teltumbde PA, et al. Intra-articular injections of ketamine and 25% dextrose improve clinical and pathological outcomes in the monosodium iodoacetate model of osteoarthritis. Journal of basic and clinical physiology and pharmacology. 2017;28:543−53.
8. Lu W, Wang L, Wo C, Yao J. Ketamine attenuates osteoarthritis of the knee via modulation of inflammatory responses in a rabbit model. Molecular medicine reports. 2016;13:5013−20.
9. Hocking G, Cousins MJ. Ketamine in Chronic Pain Management: An Evidence-Based Review. Anesth Analg. 2003;97:1730−9.
10. Lange M, Broking K, van Aken H, Hucklenbruch C, Bone HG, € Westphal M. Role of ketamine in sepsis and systemic inflammatory response syndrome. Anaesthesist. 2006;55:883−91.
11. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016;55:1059−77.
12. Combe R, Bramwell S, Field MJ. The monosodium iodoacetate model of osteoarthritis: A model of chronic nociceptive pain in rats? Neurosci Lett. 2004;370:236−40.
13. Fernihough J, Gentry C, Malcangio M, et al. Pain related behaviour in two models of osteoarthritis in the rat knee. Pain. 2004;112:83−93.
14. Kalff KMM, El Mouedden M, van Egmond J, et al. Pre-treatment with capsaicin in a rat osteoarthritis model reduces the symptoms of pain and bone damage induced by monosodium iodoacetate. Eur J Pharmacol. 2010;641:108−13.
15. Bove SE, Calcaterra SL, Brooker RM, et al. Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis. Osteoarthritis Cartilage. 2003;11:821−30.
16. Vivancos GG, Verri WA, Cunha TM, et al. An electronic pressuremeter nociception paw test for rats. Braz J Med Biol Res. 2004;37:391−9.
17. Ramage L, Martel MA, Hardingham GE, Salter DM. NMDA receptor expression and activity in osteoarthritic human articular chondrocytes. Osteoarthritis Cartilage. 2008;16:1576−84.
18. Knights CB, Gentry C, Bevan S. Partial medial meniscectomy produces osteoarthritis pain-related behaviour in female C57BL/6 mice. Pain. 2012;153:281−92.
19. Chandran P, Pai M, Blomme EA, Hsieh GC, Decker MW, Honore P. Pharmacological modulation of movement-evoked pain in a rat model of osteoarthritis. Eur J Pharmacol. 2009;613:39−45.
20. Lee CH, Wen ZH, Chang YC, et al. Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes. Osteoarthritis Cartilage. 2009;17:1485−93.
21. Gerwin N, Bendele AM, Glasson S, Carlson CS. The OARSI histopathology initiative ‒ recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis Cartilage. 2010;18(Suppl 3):S24−34.
22. Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K. MonoIodoacetate-Induced Histologic Changes in Subchondral Bone and Articular Cartilage of Rat Femorotibial Joints: AN Animal Model of Osteoarthritis. Toxicol Pathol. 2003;31:619−24.
23. Pomonis JD, Boulet JM, Gottshall SL, et al. Development and pharmacological characterization of a rat model of osteoarthritis pain. Pain. 2005;114:339−46.
24. Lee Y, Pai M, Brederson JD, et al. Monosodium iodoacetateinduced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord. Mol Pain. 2011;7:39.
25. Boettger MK, Weber K, Gajda M, Brauer R, Schaible HG. Spinally € applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis. Brain Behav Immun. 2010;24:474−85.
26. Weinbroum AA. Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. Pharmacol Res. 2012;65:411−29.
27. Trimmel H, Helbok R, Staudinger T, Jaksch W, Messerer B, Schochl H, et al. S(+)-ketamine : Current trends in emergency € and intensive care medicine. Wiener klinische Wochenschrift. 2018;130:356−66.
28. Huang C, Li HT, Shi YS, Han JS, Wan Y. Ketamine potentiates the effect of electroacupuncture on mechanical allodynia in a rat model of neuropathic pain. Neurosci Lett. 2004;368:327−31.
Submitted date:
03/21/2023
Accepted date:
03/04/2024
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email