Acute Pain Management in Patients With Opioid Tolerance

Adebola Adesoye, PharmD, BCPS; Nakia Duncan, PharmD, BCGP, BCPS


US Pharmacist. 2017;42(3):28-33. 

In This Article


The sensation of pain occurs via nociception, a process of communication between the site of tissue damage and the central nervous system (CNS).[8,9] A noxious stimulus (mechanical, thermal, or chemical) activates nociceptors, or free nerve endings (A-delta and C fibers), in the peripheral nerves.[9] This stimulus is then transduced into a sensor potential that, if high enough, triggers action potential that is transmitted down the axon to nerves located in the dorsal horn of the spinal cord or brainstem.[9] The nerve impulses in the dorsal horn may then travel up the ascending pathway to the thalamocortical system, where perception—including information on location, intensity, and duration—occurs.[8,9] Pain modulation takes place via the descending pathway from the brain to the neurons in the dorsal horn of the spinal cord.[8,9]

Neuropathic pain differs from nociceptive pain in that neuropathic pain results from abnormal processing of nerve impulses in the peripheral nervous system and CNS, whereas nociceptive pain results from noxious stimulation of free nerve endings in the tissue.[8,9]

It is theorized that, with chronic opioid exposure, extensive adaptations occur at the cellular and synaptic levels, leading to opioid tolerance.[4] Opioid tolerance is thought to develop from the desensitization, internalization, and downregulation of opioid receptors.[4] This phenomenon should not be confused with opioid addiction, in which a physical dependence results from receptor counteradaptation in conjunction with a drug-seeking behavior.[4]Physical dependence is a state of adaptation that is manifested by drug-specific withdrawal syndrome upon abrupt change or discontinuation of the drug.[4]

A condition that overlaps with opioid tolerance is opioid-induced hyperalgesia (OIH). However, the difference between them is that in opioid tolerance, an increased amount of opioids is necessary to relieve the pain, whereas in OIH, the same amount of opioid causes paradoxically worse pain.[5] It is important for both clinicians and patients to understand the difference between opioid tolerance and OIH.