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

PLoS One. 2021 Dec 8;16(12):e0260423. doi: 10.1371/journal.pone.0260423. eCollection 2021.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / physiopathology*
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / physiopathology*
  • Dose-Response Relationship, Drug
  • Freund's Adjuvant / adverse effects*
  • Male
  • Nociception / drug effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Freund's Adjuvant

Grants and funding

Initials of authors who received each award: Che Aishah Nazariah Ismail Grant Numbers awarded: 1) 304/PPSP/6315333 and 2) 204.PPSP.6171238 Full name of each funder: 1) Universiti Sains Malaysia 2) Ministry of Higher Education, Malaysia Did sponsors/funders play role? YES. The funders provided the grants money to cover the consumables, reagents and disposable items needed for this research.