Antinociceptive Investigations of Niranthin in Complete Freund’s Adjuvant-induced Chronic Pain in Mice

The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund’s adjuvant (CFA) induced pain model. The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 & 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours. Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity. This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain.

Appraisal of Anti-Arthritic Potential of Quercus Leucotrichophora Methanolic Extract in Complete Freund’s Adjuvant Induced Arthritic Rats; a Mechanistic Study

This research work was conducted to validate the folkloric use and therapeutic potential of Quercus leucotrichophora (QL) leaf methanolic and aqueous extracts against inflammation and arthritis and to determine the chemical composition by HPLC. The in-vitro anti-oxidant and anti-inflammatory activities were carried out along with in-vivo assays such as carrageenan induced paw edema, xylene induced ear edema and Complete Freund’s Adjuvant induced arthritis in Wistar rats. The CFA (0.1 ml) was inoculated to the left hind paw at day 1 to induce arthritis and oral dosing with QLME at 150, 300 and 600 mg/kg was begun at 8th day till the 28th day in all groups while methotrexate was given as standard treatment. There was a noteworthy (p<0.05-0.0001) restoration in body weight, paw edema, arthritic index, altered blood parameters and oxidative stress biomarkers in treated rats as compared to diseased group. Moreover, QLME considerably (p<0.0001) downregulated TNF-α, IL-6, IL-1β, COX-2, and NF-κB, while significantly (p<0.0001) upregulated IL-10, I-κB, IL-4 in relation to diseased group. The QLME exhibited no mortality in acute toxicity study. It was concluded that QLME possessed substantial anti-inflammatory and anti-arthritic potential at all dosage levels, mainly at 600 mg/kg might be due to presence of quercetin, sinapic acid and ferulic acid.

Effects of different doses of complete Freund’s adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis

Complete Freund’s adjuvant (CFA) has been used to develop the arthritic or inflammatory condition in the animal, but there is a lack of information concerning high CFA doses on nociceptive behaviour and inflammatory parameters. This study aimed to compare the effects of different high doses of CFA in rat to closely mimic nociceptive and inflammatory parameters of rheumatoid arthritis (RA) in humans. Twenty-four male Sprague-Dawley rats were randomly divided into four groups (n = 6): Control (C), CFA-induced polyarthritic groups at 5.0 mg/mL (CFA 5.0), 7.5 mg/mL (CFA 7.5) and 10.0mg/mL (CFA 10.0). The rats’ right hindpaw was inoculated with CFA intradermally and developed into a polyarthritic state within 20 days. Nociceptive behavioural assessments, including von Frey and hot plate tests and spontaneous activities, were conducted on day 0, 7, 15 and 20. Bilateral ankle joints diameter and circumference, full blood count, joints and paw histological examinations were also conducted throughout the study period. Based on the results, CFA 5.0 and CFA 7.5 groups showed a significant increase in spontaneous activities and development of thermal hyperalgesia but no change in body weight and food intake, no development of tactile allodynia and haematological indices, and no significant morphological changes of joints histology. Meanwhile, CFA 10.0 group demonstrated significant and constant changes in all nociceptive and inflammatory parameters investigated. In conclusion, CFA at the dose of 10mg/mL has the most potential and reliable dosage to develop polyarthritis in a rat model to mimic RA condition in humans.

Anti-Inflammatory Effects of BoNT/A Against Complete Freund’s Adjuvant-Induced Arthritis Pain in Rats: Transcriptome Analysis

Arthritis is the most common cause to lead to chronic pain. Botulinum toxin type A (BoNT/A) has been widely used to treat chronic pain. In our previous study, we confirmed the anti-inflammatory and antinociceptive effects of BoNT/A in the Complete Freund’s Adjuvant (CFA)-induced arthritis model, but the underlying anti-inflammatory mechanism was not fully elucidated. The purpose of this study was to investigate the anti-inflammatory effects and mechanisms of BoNT/A on arthritis using transcriptomic analysis. The BoNT/A was injected into the rat ankle joint on day 21 after CFA injection. The von Frey and hot plate tests were applied to assess the pain-related behaviors at different time points. Five days after BoNT/A treatment, gene expression profiling in dorsal root ganglion (DRG) was performed using RNA sequencing (RNA-seq). The differentially expressed genes (DEGs) were analyzed by various tools. The mechanical allodynia and thermal hyperalgesia were significantly reversed after BoNT/A injection. RNA-seq revealed 97 DEGs between the CFA group and Sham group; these DEGs were enriched inflammatory response, IL-17 signaling pathway, etc. There are 71 DEGs between the CFA+BoNT/A group and the CFA group; these DEGs related to response to peptide, PI3K-Akt signaling pathway, ECM–receptor interactions, etc. Three key genes were significantly decreased after CFA-induced arthritis pain, while BoNT/A increased the expression of these genes. The identification of S100A9, S100A8, and MMP8 genes can provide new therapeutic targets for arthritis pain and affect the signaling pathway to play an anti-inflammatory role after the treatment of BoNT/A.

Amelioration of complete Freund’s adjuvant-induced arthritis by Calotropis procera latex in rats

Background Rheumatoid arthritis is the most common cause of disability, affecting 0.3–1% of the adult population worldwide. The latex of Calotropis procera possesses potent anti-inflammatory as well as analgesic properties. In light above facts, the present study was designed to evaluate anti-arthritic activity of Calotropis procera latex in complete Freund's adjuvant (CFA)-induced arthritis in Wistar albino rats. Complete Freund's adjuvant was injected into the left hind paw on day 0, and treatment of prednisolone and Calotropis procera latex was given from day 0 to 28. Various biochemical, hematological and functional parameters as well as radiological and histopathological changes of joint along with body weight and paw volume were measured. Results Calotropis procera treatment significantly lowered paw volume in CFA-induced arthritic rats. Significant improvement was observed in functional, biochemical and hematological parameters in Calotropis procera-treated rats. However, the body weight remained unaffected. Histological and radiographical examination of synovial joints in Calotropis procera-treated animals exhibited less synovial hyperplasia, infiltration and accumulation of inflammatory cell in synovial fluid, cartilage and bone erosion and joint space narrowing. Conclusion Calotropis procera latex possesses anti-arthritic activity, which is facilitated by modulation in the level of inflammatory mediators and oxidative stress. The improvement in hematological as well as biochemical parameters might be reflected on functional, histopathological, radiological changes and thereby disease progression.

ERDOSTEINE: AN EFFECTIVE ANTIOXIDANT FOR PROTECTING COMPLETE FREUND’S ADJUVANT INDUCED ARTHRITIS IN RATS

Objective: The objective of this study was to evaluate the protective effect of Erdosteine on complete freund’s adjuvant (CFA) induced arthritic rats. Methods: Wistar Albino rats of 100–250 g were divided into five groups (n=6) and administered with 0.1 ml of CFA subcutaneously into the left hind paw except the negative control group. The standard group received methotrexate (MTX) 0.075 mg/kg body weight orally. Besides, the test groups received Erdosteine orally at a dose 10 mg/kg and 20 mg/kg bodyweight for 12 days. The changes in body weight, paw volume, hematological parameters, radiographical, and histological findings were the indicators to evaluate the efficacy of the test product. Discussion: Significant change in the body weight, paw volume, radiographical, hematological, and histological parameters were observed which supports the remarkable reduction of the arthritic development in the standard and test groups compared to the untreated group. However, the test group (Erdosteine) with the dose 20 mg/kg shows to be more potent than the test group (Erdosteine) with a dose 10 mg/kg and the standard group (MTX) to reduce the arthritic effect. Results: The test group with 20 mg/kg Erdosteine showed much better outcome than the standard group at significant (p<0.05). Therefore, Erdosteine acting as an anti-inflammatory and anti-oxidant is effective at a dose 20 mg/kg in treating the progression of rheumatoid arthritis in rats.