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. 2024 May-Jun;74(3):844502.
doi: 10.1016/j.bjane.2024.844502. Epub 2024 Apr 9.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study

Eugênio Dos Santos Neto  1 , Pedro Paulo de Alcantara Pedro  2 , Maria do Socorro de Sousa Cartágenes  3 , José Osvaldo Barbosa Neto  4 , João Batista Santos Garcia  5
Affiliations

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study

Eugênio Dos Santos Neto et al. Braz J Anesthesiol. 2024 May-Jun.

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.

Irb approval number: 23115 012030/2009-05.

Keywords: Animal models; Osteoarthritis; S(+)-Ketamine; Synovial Membrane; Synovitis.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Study flowchart.
Figure 2
Figure 2
Results concerning the impact of S(+)ketamine in the experimental tests conducted within this study. (A) Forced Ambulation. (B) Hind Leg Weight Distribution. (C) Paw Withdrawal (Mechanical Allodynia). (D) Paw Withdrawal (Mechanical Hyperalgesia). Vertical symbols and lines denote the mean and standard error of means. The vertical dashed line signifies the beginning of treatment. * Significant difference between the OA-Saline group and the Non-OA group. ° Significant difference between the OA-Ketamine group and the Non-OA group. # Significant difference between the OA-Ketamine group and the OA-Saline group. Statistical significance: p < 0.05.
Figure 3
Figure 3
Grip force assessment in rats treated with S(+)-ketamine (n = 6). The data is presented as the nociceptive paw withdrawal threshold in percentage. Vertical symbols and lines indicate the mean and standard error of the means. ANOVA ‒ Tukey's test was performed (p < 0.05). The vertical dashed line signifies the beginning of treatment. *Significant difference between the OA-Saline group and the Non-OA group. °Significant difference between the OA-Ketamine group and the Non-OA group. #Significant difference between the OA-Ketamine group and the OA-Saline group.
Figure 4
Figure 4
Photomicrograph of the synovial membrane in an experimental model of MIA-induced osteoarthritis. OA-Saline Group (A to D), OA-Ketamine Group (E to H), and NON-OA Group (I to L) stained with hematoxylin and eosin. Notable changes in D show synovial cell proliferation, subsynovial tissue growth, and inflammatory cell infiltration, classified as Grade 4. Grade 0 inflammation score is observed in L, while a Grade 3 inflammation score is seen in C. Magnification: 100 ×.
See this image and copyright information in PMC

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. - PubMed
    1. Lorenz H, Richter W. Osteoarthritis: cellular and molecular changes in degenerating cartilage. Prog Histochem Cytochem. 2006;40:135–163. - PubMed
    1. 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. - PMC - PubMed
    1. 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;44:2068–2080. - PubMed
    1. Matta C, Juhász T, Fodor J, Hajdú T, Katona É, Szűcs-Somogyi C, et al. N-methyl-D-aspartate (NMDA) receptor expression and function is required for early chondrogenesis. Cell Commun Signal. 2019;17:166. - PMC - PubMed