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Why Opioids Backfire With Repeated Use With repeated exposure, the nervous system adapts to opioids, leading to: Tolerance , requiring higher doses for the same effect (33,35) Dependence , with withdrawal symptoms when doses wear off (35) Opioid-induced hyperalgesia , a paradoxical increase in pain sensitivity (33,36) Rather than calming pain long term, opioids can sensitize the nervous system, making everyday stimuli feel more painful (33,36)

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3, Table S1)