Spontaneous and Evoked Measures of Pain in Murine Models of Monoarticular Knee Pain

Abstract

Pain is the main cause of disability from arthritis. There is currently an unmet need for adequate treatments for arthritis pain. Pre-clinical models are necessary and useful for studying the mechanisms of pain and for evaluating efficacy of arthritis therapies. Measuring pain in animal models of arthritis is challenging. We have developed methods for measuring evoked and spontaneous pain in three models of murine arthritis. We quantitate the evoked pain responses of mice subjected to firm palpation of a painful knee. We also evaluate spontaneous pain by the proportion of weight and the amount of time placed on each of their 4 limbs after induction of arthritis pain in one knee. Joint pain in these mouse models produces a significant increase in evoked pain responses and an alteration in weight bearing. Since mice are quadrupeds, they offload the painful limb to the contralateral limb, to the forelimbs, or some combination. These methods are simple, require minimal equipment, and are reproducible and sensitive for detecting pain. They are useful for studying both disease-modifying arthritis treatments and analgesics in mice.

The molecular mechanism and physiological role of silent nociceptor activation

“…To induce inflammatory knee joint pain the Complete Freund’s Adjuvant (CFA)-induced knee joint monoarthritis model was used as previously described 53 . In brief, animals were anesthetized in a transparent plexiglass chamber filled with 4% isoflurane in 100% O2 at a flow rate of 1.0 L/min for 3 min.…”

Role of TMEM100 in mechanically insensitive nociceptor un-silencing

“…To induce inflammatory knee joint pain the Complete Freund's Adjuvant (CFA)-induced knee joint monoarthritis model was used 53 . In brief, animals were anesthetized in a transparent plexiglass chamber filled with 4% isoflurane in 100% O2 at a flow rate of 1.0 L/min for 3 min.…”