Background & Aims

Joint pain is a highly complex phenomenon encompassing varying levels of nociceptive, inflammatory, and neuropathic aspects [1]. Furthermore, the prevalence of arthritis is skewed in favour of females, yet it is still unclear whether joint nociception differs between the sexes. Behavioural assessment of joint pain in animal models is hampered by the subjectivity of the experimental approaches employed which can affect interpretation of the data [2]. Electrophysiological recording from joint nociceptors in preclinical models permits an objective measurement of joint nociception without experimental bias. The current study characterized the electrophysiological properties of knee joint nociceptors in three rat models of joint disease.

Methods

Male and female Wistar rats (200-350g) were assigned to one of three experimental groups. All animals were deeply anaesthetised with inhaled isoflurane (2% in 100% O2 at 1L/min). For model 1 (chemically-induced osteoarthritis), animals received an intra-articular injection of sodium monoiodoacetate (MIA; 3mg in 50µL of 0.9% saline) into the right knee and allowed to recover for 14 days. Model 2 (joint neuropathy) animals received an intra-articular injection of lysophosphatidic acid (LPA, 100µg in 50µL of 5% ethanol/saline) with a recovery period of 21 days. In model 3 (surgically-induced osteoarthritis), rats underwent midsubstance transection of the right knee medial meniscus to induce joint instability. Osteoarthritis developed over the proceeding 28 days. A separate cohort of weight-matched naïve rats constituted the control groups. Single unit, extracellular, electrophysiological recordings were then made from joint nociceptors in response to noxious rotation of the knee.

Results

Compared to naïve animals, induction of nociceptive, inflammatory, and neuropathic joint damage induces spontaneous activity of articular nociceptors (p<0.05, chi square test). The mechanical threshold of nerve activation was less than what was observed in control joints (p<0.05, Kruskal-Wallis test) except for male LPA and female MIA (p>0.05, Kruskal-Wallis test). Finally, the firing rate of joint afferents was significantly increased in all models indicative of peripheral sensitization (p>0.05, Kruskal-Wallis test). These changes in neurophysiological properties were similar in male and female animals.

Conclusions

These data unequivocally confirm that pro-nociceptive activity occurs in joint nociceptors during the development of osteoarthritis. Silent nociceptors become spontaneously active, the mechanical threshold for neuronal activation is reduced, and the firing frequency of the nociceptors is also elevated. There was no difference in nociceptive responses between the models or between the sexes. Thus, in vivo recording from joint mechanosensitive afferents provides a robust, objective means of measuring joint nociception permitting further investigation into the neurobiology of osteoarthritis.

References

1. McDougall, J. J. Arthritis and Pain. Neurogenic origin of joint pain. Arthritis Research and Therapy 8, 220-229 (2006).

2. O’Brien, M., Philpott, H. T. & McDougall, J. J. Understanding osteoarthritis pain through animal models. Clin Exp Rheumatol 35 Suppl 107, 47-52 (2017).

Presenting Author

Melissa O'Brien

Poster Authors

Jason McDougall

BSc PhD

Dalhousie University

Lead Author

E-mail

Topics

  • Models: Musculoskeletal