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