Investigating Brain Abnormalities in People With Knee Osteoarthritis Using MRI: a Nociplastic Pain Mechanism Based Assessment

Chronic pain and knee osteoarthritis - context and gap

Chronic pain is a debilitating concern that can affect the health, employment, and lifestyle of individuals and puts a tremendous strain on the healthcare system. The prevalence of osteoarthritis (OA) is estimated at over 650 million worldwide, and people with knee OA account for 80% of the total burden (Cui et al. 2020). Globally in 2017, knee OA had a prevalence of 263,086,500 and incidence of 12,888,400 (James et al. 2018). A recent study also found that between 19%-43% of adults 40 years and older had knee OA markers, detected using magnetic resonance imaging (MRI), but were asymptomatic (Culvenor et al. 2019). It is estimated that more than 10 million Canadians will have knee OA by the year 2040 (Bombardier et al. 2011) significantly contributing to OA healthcare costs of 1.45 trillion (Bombardier et al. 2011; Sharif et al. 2017). The severity of pain and its impact on function have been identified by people living with knee OA as two of the most important effects of the disease (Smith et al. 2014), contributing to reduced quality of life (Neogi et al. 2013). Uncontrolled OA joint pain is associated with increased healthcare use, therefore improving pain management for OA in Canada may result in a significant healthcare expenditure savings of up to $488 billion (Bombardier et al. 2011). The pain experience and its associated mechanisms in people with knee OA are known to be complex, with alterations in pain signalling (Fingleton et al. 2015) a major factor in susceptibility to the development of persistent pain (Carlesso et al. 2019). Changes in nervous system sensitization do not necessarily correlate with changes in pain, demonstrating that other factors modulating pain, a top-down process, are at play (Skou et al. 2016; Edwards et la. 2016). Interestingly, between 10-20% of knee OA patients continue to experience intense pain even after a total knee replacement indicating that mechanisms beyond those involving joint structures are likely contributing to a complex pain process (Baker et la. 2007; Lundblad et al. 2008; Rice et al. 2018). In a disease where the joint is viewed as an organ in failure (Loeser et al. 2012), phenotyping is necessary to make sense of the heterogeneity. Specific to knee osteoarthritis (OA), pain is associated with changes in the joint structure due to inflammation (e.g., synovitis)(Dainese et al. 2022) or bone marrow lesions (Aso et al. 2021), but the underlying mechanisms are not fully understood (Gwilym et al. 2008).

Nociceptive, neuropathic, and nociplastic pain

In general, pain of known origin falls under two categories based on the cause: (i) nociceptive: pain caused by damage to a bodily tissue; (ii) neuropathic: pain caused by damage to a nerve or nervous system. However, chronic pain that is present without discernable nociceptive or neuropathic components is classified as nociplastic pain (IASP 2022). A recent study by Kosek et al. (2021) developed a simple scale for nociplastic pain diagnosis for clinical pain assessment based on i) the duration/regionality/type of pain, ii) history of hypersensitivities, iii) comorbidity identification, and iv) evoked pain hypersensitivity (Kosek et al 2021). As a visual representation, the Michigan Body Map (MBM) has been validated as a rapid and reliable tool for patients to identify general bodily regions where they experience chronic pain (Brummett et al. 2016). The MBM is a useful and simple tool to determine if pain is localized (i.e., likely nociceptive or neuropathic pain) or widespread (i.e., likely nociplastic pain)(Brummett et al. 2016). To address the unknown chronic pain mechanisms and pain presenting beyond nociceptive or neuropathic injuries, research has been focused on the theory of central sensitization as a phenomenon of nociplastic pain (Fitzcharles et al. 2021; Walsh 2021). The concept of central sensitization is that dysfunction in the central nervous system results in hypersensitivity to noxious and innocuous stimuli (de Boer et al. 2019; Neblett et al. 2013).

Current methods for nociplastic pain assessment