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How Pain Medications May Reinforce Nervous System Sensitivity Several commonly used pain medications influence nervous system signaling in ways that may unintentionally reinforce pain over time: Opioids can increase pain sensitivity through opioid-induced hyperalgesia Corticosteroids alter stress-hormone signaling and sleep architecture NSAIDs may impair tissue repair, prolonging nociceptive input Acetaminophen reduces antioxidant capacity needed for neuronal resilience When combined with chronic stress, poor sleep, nutrient depletion, or unresolved inflammation, the nervous system may lose its ability to turn pain off. When Pain Becomes a Conditioned Neurologic Response Over time, pain can become conditioned linked not only to tissue injury, but also to: Movement patterns Emotional stress Previous flare experiences Sleep disruption At this stage, pain is maintained by neural patterning rather than active structural damage

Moreover, it has been reported that Rheb undergoes K48-linked polyubiquitination under low glucose availability, leading to the inactivation of mTORC1 (Li et al, 2024), which suggests the essentiality of regulating Rheb levels and activity during glucose starvation