Background/Purpose:

Osteoarthritis (OA) is the leading cause of chronic pain in European adults (37%; painineurope.com). Pain is the foremost symptom of OA, with both episodes and severity becoming more constant or frequent with progression of the disease. Current therapies to reduce pain are often ineffective and have use limiting side effects. Thus the development of efficacious analgesics is crucial to improve the lives of individuals with OA, to this end the use of animal models is required to understand the underlying mechanisms of OA-induced chronic pain. We aimed to further characterize the partial medial menisectomy model of OA, by assessing the development of hypersensitivity to mechanical stimulus, the impact on burrowing behaviour, and the response to Gabapentin a known analgesic used in the treatment of neuropathic pain, in both young and aged adult male and female mice.

Methods:

C57/Black6J male and female mice approx. 3-4 or 16-18 months of age at the time of surgery were randomized into partial medial menisectomy or sham surgery groups, all groups received post-operative analgesia of buprenorphine. Hypersensitivity to mechanical stimulus was assessed using von Frey filaments applied to the hindpaw, to determine secondary mechanical allodynia. Burrowing behaviour was used as an outcome measure of general wellbeing and is thought to reflect ongoing pain. All behaviour was monitored before and up to 16-30 weeks post-surgery. Mechanical allodynia was assessed following administration of Gabapentin (50mg/kg; i.p.). Osteoarthritic pathology of the knee joints were analyzed by hematoxylin and eosin and/or Safranin-O staining.

Results:

In both aged (14 weeks post-surgery) and young (27 weeks post-surgery) female groups significant development of mechanical hypersensitivity and signs of osteoarthritic pathology (cartilage loss) were observed. Mechanical hypersensitivity was not observed in young adult male mice and less pronounced in aged male compared to aged female mice. Mechanical hypersensitivity in female mice was significantly reversed by Gabapentin. No significant deficit in burrowing behaviour was noted between the groups.

Conclusion:

The partial medial menisectomy model is a slowly developing model of OA-induced mechanical hypersensitivity in adult female mice (with earlier onset in aged mice), which is reversible by Gabapentin. No deficit in burrowing suggests this model does not have a negative impact on the overall wellbeing or lead to ongoing pain for the mice. This model reflects the clinical condition and could aid the translation of preclinical findings into clinical outcomes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/age-and-sex-impacts-the-development-of-hypersensitivity-in-the-murine-partial-medial-menisectomy-model-of-osteoarthritis/