Experimental models to study osteoarthritis pain and develop therapeutics

Kanyakorn Riewruja; Meagan Makarczyk; Peter G Alexander; Qi Gao; Stuart B Goodman; Bruce A Bunnell; Michael S Gold; Hang Lin

doi:10.1016/j.ocarto.2022.100306

Experimental models to study osteoarthritis pain and develop therapeutics

Osteoarthr Cartil Open. 2022 Aug 13;4(4):100306. doi: 10.1016/j.ocarto.2022.100306. eCollection 2022 Dec.

Authors

Kanyakorn Riewruja^{1

2}, Meagan Makarczyk^{1

3}, Peter G Alexander¹, Qi Gao⁴, Stuart B Goodman⁴, Bruce A Bunnell⁵, Michael S Gold⁶, Hang Lin^{1

3}

Affiliations

¹ Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
² Osteoarthritis and Musculoskeleton Research Unit, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, 10330, Thailand.
³ Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, USA.
⁴ Department of Orthopaedic Surgery, Stanford, CA, USA.
⁵ Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.
⁶ Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Abstract

Pain is the predominant symptom of osteoarthritis (OA) that drives patients to seek medical care. Currently, there are no pharmacological treatments that can reverse or halt the progression of OA. Safe and efficacious medications for long-term management of OA pain are also unavailable. Understanding the mechanisms behind OA pain generation at onset and over time is critical for developing effective treatments. In this narrative review, we first summarize our current knowledge on the innervation of the knee joint, and then discuss the molecular mechanism(s) currently thought to underlie OA pain. In particular, we focus on the contribution of each joint component to the generation of pain. Next, the current experimental models for studying OA pain are summarized, and the methods to assess pain in rodents are presented. The potential application of emerging microphysiological systems in OA pain research is especially highlighted. Lastly, we discuss the current challenge in standardizing models and the selection of appropriate systems to address specific questions.

Keywords: Microphysiological system; Nerve; Osteoarthritis; Pain; Pain mediators; Tissue chip.

Publication types

Review

Grants and funding

T32 EB001026/EB/NIBIB NIH HHS/United States