Fibromyalgia: Genetics and epigenetics insights may provide the basis for the development of diagnostic biomarkers

Fibromyalgia is a disease characterized by chronic widespread pain with additional symptoms, such as joint stiffness, fatigue, sleep disturbance, cognitive dysfunction, and depression. Currently, fibromyalgia diagnosis is based exclusively on a comprehensive clinical assessment, according to 2016 ACR criteria, but validated biological biomarkers associated with fibromyalgia have not yet been identified. Genome-wide association studies investigated genes potentially involved in fibromyalgia pathogenesis highlighting that genetic factors are possibly responsible for up to 50% of the disease susceptibility. Potential candidate genes found associated to fibromyalgia are SLC64A4, TRPV2, MYT1L, and NRXN3. Furthermore, a gene-environmental interaction has been proposed as triggering mechanism, through epigenetic alterations: In particular, fibromyalgia appears to be characterized by a hypomethylated DNA pattern, in genes implicated in stress response, DNA repair, autonomic system response, and subcortical neuronal abnormalities. Differences in the genome-wide expression profile of microRNAs were found among multiple tissues, indicating the involvement of distinct processes in fibromyalgia pathogenesis. Further studies should be dedicated to strength these preliminary findings, in larger multicenter cohorts, to identify reliable directions for biomarker research and clinical practice

Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment

Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking. In this work, we used the monosodium iodoacetate model of osteoarthritis in adult (11-week-old) and old (20-month-old) C57BL/6J mice to compare hypersensitivity, locomotion, neuroinflammation, and the effects of morphine treatment. After osteoarthritis induction in adult and old mice, weight-bearing asymmetry, mechanical allodynia, and thermal hyperalgesia similarly developed, while locomotion and frailty were more affected in old than in adult animals. When behavioral deficits were present, the animals were treated for 7 days with morphine. This opioid counteracts the behavioral alterations and the frailty index worsening both in adult and old mice. To address the mechanisms that underlie pain, we evaluated neuroinflammatory markers and proinflammatory cytokine expression in the sciatic nerve, DRGs, and spinal cord. Overexpression of cytokines and glia markers were present in osteoarthritis adult and old mice, but the activation was qualitatively and quantitatively more evident in aged mice. Morphine was able to counteract neuroinflammation in both age groups. We demonstrate that old mice are more vulnerable to pain’s detrimental effects, but prompt treatment is successful at mitigating these effects