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Depressive symptoms are common in individuals with multiple sclerosis (MS), and are frequently exacerbated by pain; however, spiritual well-being may allow persons with MS to more effectively cope with pain-related deficits in physical and role functioning. We explored the associations between spiritual well-being, pain interference and depressive symptoms, assessing each as a potential mediator, in eighty-one patients being treated for MS, who completed self-report measures: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale, Pain Effects Scale, and Center for Epidemiologic Studies Depression Scale Revised. At the bivariate level, spiritual well-being and its subscale of meaning and peace were negatively associated with depression and pain interference. In mediation models, depression was not related to pain interference via spiritual well-being, or to spiritual well-being via pain interference. Pain interference was related to depression via spiritual well-being and meaning/peace, and to spiritual well-being and meaning/peace via depressive symptoms. Finally, spiritual well-being and meaning/peace were related to depression via pain interference, and to pain interference via depressive symptoms. For patients with MS, a multi-faceted approach to treatment that includes pain reduction and promotion of spiritual well-being may be beneficial, although amelioration of depression remains a critical task.

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