**1. Introduction**

Musculoskeletal diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA), are the leading causes of years lived with disability (YLD) worldwide. Furthermore, YLD due to OA increased by 31.5% from 2006 to 2016, in association with the aging of the population [1]. Pain is the cardinal symptom of both OA and RA, which directly affects the decision to seek medical care. In addition, pain is closely related to function and quality of life, such that knee pain is a better predictor of disability than radiographic changes in OA [2,3]. The development of effective therapeutics for optimal pain management has lagged behind other areas, such as inflammation control and the regulation of autoimmunity, which is partially responsible for the current epidemic of opioid and narcotic abuse. A recent report showed that nearly 10% of all opioids prescribed in Australian general practice are prescribed for OA [4]. Similarly, in a survey of Swedish residents aged ≥35 years, 12% of incident opioid dispensations were attributable to OA and/or its related comorbidities [5]. Although there is inconclusive evidence for the benefits of opioids for arthritides and increasing awareness of the risks, opioid prescription rates for OA in the USA remained stable between 2007 and 2014 [6]. On the other hand, despite recent advances in the treatment of RA utilizing effective immunosuppressive therapies based on a better understanding of its underlying mechanism, remaining pain affected almost one third of early RA patients with a good clinical response [4]. By 2014, 41% of patients with RA in the USA were regular users of opioids [7]. Therefore, to optimize the care of patients with OA

and RA, the elucidation of the mechanisms underlying the pathogenesis of pain in these diseases is of great importance. Intuitively, pain from arthritis arises from direct nociceptive mechanisms, such as inflammation and structural joint damage. However, in addition to nociception, arthritis pain involves diverse mechanisms, including the processing of pain in the nervous system, as well as psychological distress [8]. Several well-established animal models of OA and RA are available to study the mechanisms underlying the pathogenesis of joint damage and immune/inflammatory regulation. A range of behavioral and neurophysiological approaches have been used for the delineation of pain in animal models of arthritis. Due to the inherent technological challenges in the quantitative assessment of pain in animal models, however, caution is required when attempting to extrapolate discoveries made in animal models to human patients. This review discusses biological and molecular mechanisms underlying the pathogenesis of arthritis pain obtained in animal models of OA and RA along with the methodologies used.
