121: Centralisation of pain behaviour in the monoiodoacetate model of osteoarthritis in rats.

Topic: Basic Science
Subtopic: Pain category (ICD-11), Acute musculoskeletal pain, , , , , , , , , , Pharmacological interventions, Electrophysiology, Behavioral studies

Background and Aims: Pain in osteoarthritis (OA) is not adequately treated clinically, with promising new analgesic treatments failing to translate. Possible reasons include that it is unclear how well animal models replicate human OA and which preclinical pain behaviour assays are the most useful indicators of pain in OA patients. Monoiodoacetate (MIA)-induced OA is the most used animal model to assay OA pain, however it is unclear how sensitive it is for testing drugs that act on peripheral nociceptors in OA. We aimed to identify pain behaviour assays suitable for measuring the activity of drugs that act on peripheral nociceptors in MIA-induced OA.

Methods: To determine the sensitivity of assays to detect changes in pain behaviour after induction of OA, we compared the effect of intra-articular injections of MIA or saline on dynamic weight-bearing, locomotor activity and withdrawal to pressure application at the joint . Testing was performed at days 3 (early inflammatory phase of MIA-induced OA) and 28 (late MIA-induced OA when cartilage and bone changes are obvious) after injection. We administered ropivacaine intra-articularly and around the sciatic nerve to further test for contributions of the peripheral nervous system, and we administered buprenorphine subcutaneously to test for central nervous system contributions on pain behaviours.

Results: Weight bearing and withdrawal thresholds to pressure application at the joint, but not locomotor activity, were significantly reduced (two-way ANOVA with repeated measures; Bonferroni’s multiple comparisons; P<0.05 ) at both early and late-MIA induced OA. A single intra-articular or sciatic nerve dose of ropivacaine was unable to reverse changes in pain behaviour, except for changes in withdrawal thresholds to pressure application at early MIA-induced OA (Student t-test; P<0.05). However, buprenorphine reversed all of the changes in pain behaviour that ropivacaine was unable to (Student t-test; P<0.05).

Conclusions: These data indicate that pain behaviour is rapidly centralised in MIA-induced OA, with spontaneous pain behaviours such as weight-bearing centralised prior to evoked behaviours such as withdrawal to pressure application to the joint. Further the pain behaviour assays used in this study are not sensitive enough for testing singles doses of short acting drugs that act on peripheral nociceptors in the MIA-induced model of OA.

References: NA

Presenting Author: Michael Morgan
Submitting Author: Michael Morgan

Senior Author: Jason J Ivanusic

IASP 2026 Global Year theme of Neuropathic Pain: No

• Xiong Gao: PhD - University of Melbourne
• Jenny Thai: BSc (Hons) - University of Melbourne
• Jackson Hart: BBiomed (Hons) - University of Melbourne
• Jacob Bos - University of Melbourne
• Jason J Ivanusic: PhD - University of Melbourne