Supraspinal neuroinflammation and anxio-depressive-like behaviors in young- and older- adult mice with osteoarthritis pain: the effect of morphine

Rationale: Asteoarthritis (OA) is a leading cause of chronic pain in the elderly population and is often associated with emotional comorbidities such as anxiety and depression. Despite age is a risk factor for both OA and mood disorders, preclinical studies are mainly conducted in young adult animals. Objectives: Here, using young adult (11-week-old) and older adult (20-month-old) mice, we evaluate in a monosodium-iodoacetate-(MIA)-induced OA model the development of anxio-depressive-like behaviors and whether brain neuroinflammation may underlie the observed changes. We also test whether an effective pain treatment may prevent behavioral and biochemical alterations. Methods: Mechanical allodynia was monitored throughout the experimental protocol, while at the end of protocol (14 days), anxio-depressive-like behaviors and cognitive dysfunction were assessed. Neuroinflammatory condition was evaluated in prefrontal cortex, hippocampus and hypothalamus. Serum IFNγ levels were also measured. Moreover, we test the efficacy of a 1-week treatment with morphine (2.5 mg/kg) on pain, mood alterations and neuroinflammation. Results: We observed that young adult and older adult controls (CTRs) mice had comparable allodynic thresholds and developed similar allodynia after MIA injection. Older adult CTRs were characterized by altered behavior in the tests used to assess the presence of depression and cognitive impairment and by elevated neuroinflammatory markers in brain areas compared to younger ones. The presence of pain induced depressive-like behavior and neuroinflammation in adult young mice, anxiety-like behavior in both age groups and worsened neuroinflammation in older adult mice. Morphine treatment counteracted pain, anxio-depressive behaviors and neuroinflammatory activation in both young adult and older adult mice. Conclusions: Here, we demonstrated that the presence of chronic pain in young adult mice induces mood alterations and supraspinal biochemical changes and aggravates the alterations already evident in older adult animals. A treatment with morphine, counteracting the pain, prevents the development of anxio-depressive disorders and reduces neuroinflammation.