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Opioid-induced hyperalgesia
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Opioid tolerance
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Opioid withdrawal
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Opioid use disorder
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Mechanism
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Drug-induced pain sensitization within the CNS (central sensitization)
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Decreased drug efficacy
Desensitization of μ-receptor to opioids
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Absence of μ-receptor stimulation
Increased NE levels result in systemic symptoms
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Uncontrolled use of opioids despite adverse outcomes
Possible desensitization to opioids
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Opioid escalation
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Pain not overcome with opioid dose escalation
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Pain overcome with opioid dose escalation
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Symptomatic improvement with opioid escalation
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Variable response to dose escalation
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Other symptoms
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Pain worse with dose escalation
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Tolerance to many opioid side effects but not central apnea or constipation
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Symptoms include muscle spasm, abdominal cramp, anxiety, palpitations, and hot flashes
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Symptoms of tolerance and withdrawal, depending on the presence or lack of opioid use
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CNS: Central nervous system; NE: Norepinephrine
Adapted from Pain Manag. (2021) 11(4)