NOS2 and myalgic encephalomeyelitis/chronic fatigue syndrome: However, in ME/CFS activation of immunoinflammatory pathways and intracellular signaling networks, including NFκB, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) and CMI pathways contribute to fatigue, malaise, hyperalgesia, and autonomic and neurocognitive symptoms [12,13,95].