In summary, worse baseline mental health is associated with worse OA knee pain in a cross-sectional analysis. Furthermore, improvement in mental health from baseline is associated with reduction in pain of OA. Lastly, the risk of a pain flare is increased by worsened mental health in the week prior to the flare. These three basic findings support a strong association and possibly predictive relation between mental health and OA pain.
The rationale for examining the mental health factors and their relation to pain in OA is multifold. First, it is clear that the etiology of OA pain is not well understood, and that both peripheral and central neuronal abnormalities of function may play a part(27
). Given the importance of the central nervous system in understanding pain, and the known relation between depression or other components of mental health and intrinsic neuronal function, psychological factors become prime suspects as mediators of the experience of pain.
Second, pain in a variety of other conditions has been found to be associated with psychological state, and treatment with antidepressants has been found to alleviate pain. Tricyclic antidepressants have been demonstrated in small trials to be effective at reducing pain in rheumatoid arthritis patients(28
), but have not achieved widespread use for treatment of that disease, given the development of disease-modifying drugs for that condition; at present there are no available disease-modifying treatments for OA. Three recent meta-analyses of anti-depressant treatment for fibromyalgia have all supported the likelihood of a modest effect on pain with tricyclics(31
), but duloxetine has demonstrated a significant and repeated effect on tender points and measures of pain in randomized, controlled clinical trials(34
Lastly, there has been some preliminary evidence that treatment of depression, a powerful factor in mental health, can affect pain in OA. Lin et al.(21
) found a significant reduction in OA pain with enhancement of treatment for coexistant depression in OA patients.
Our study carries the inherent strengths of the original LEAP data. These include the first weekly independent measurements of pain and mental health in a cohort of OA patients to our knowledge. Other strengths include a plausible time frame for a causal relationship between predictor and outcome of approximately one week, convincing trends in the data that appear stable, and a case crossover analysis which demonstrates a persuasive relation to pain flares in a manner which eliminates questions of genetic, experiential, and neuronal differences between subjects. Furthermore, the differences across groups in mental health in LEAP are large. Nettles et al.(36
) state that “a change of more than 10 points [in a normalized scale of the MHI-5] was considered a significant change in mood”; a change of 10 points in the Nettles paper corresponds to a change of 2.5 points on the raw MHI-5 scale we use in this paper, which is much smaller than the change values we observed in the LEAP study.
There are also significant limitations in our study. These include combining hip and knee OA subjects into one cohort. Our most significant limitation, however, is intrinsic to the study of pain and mental health in any setting: it is quite difficult to address the spectre of reverse causality in these data. It may be true, as we have found, that mental health affects pain levels in OA. It seems intuitively true, however, that pain in OA affects mental health, and to disentangle this relationship is daunting. For example, although we have separated the independent variable from the outcome by one week in these analyses, it still may be the case that subjects have a premonition of pain they will experience the next week which could affect their mental health. Although we have tried to establish the mental health variable as predictive in our analysis, this does not negate the possibility that reverse causality plays a significant role in the results.
It may be that ultimately the question of causality is academic. There may be an iterative process at work, with an ongoing stream of OA pain and related worsened mental health that feeds back on itself over time. Certainly the cross-sectional association we have found is consistent with such a picture. It is worth considering whether entering that process at any point with a therapeutic intervention related to mental health will have the capability to abort the circular pain process. The relationship of pain to mental health may be mediated in part by a variety of factors, including social isolation, sleep changes, and changes in physical activity. We were not able to look at these questions given the information collected in the LEAP study.
In conclusion, we have shown that worse or worsening mental health precedes reporting of worse OA-related pain and OA pain flares. With the paucity of effective interventions for OA pain and the toxicities of some in common use, mental health may represent a new therapeutic target for OA pain, with potential significant opportunities for both patients and physicians.