The Evidence for Opioid-Induced Hyperalgesia Today

Hyperalgesia is an increased response to painful sensation. Opioid–induced hyperalgesia occurs after sustained opioid exposure and⁄or following abrupt cessation of opioid. At the cellular level, adenylyl cyclase superactivation and elevated cAMP levels lead to PKA–mediated enhanced neurotransmitter release. Spinal glutamate, substance P, and CGRP enhance pain through NMDA, NK–1, and CGRP receptors respectively. Non–opioid receptor mediated OIH may be caused by M3G activation of TLR4. In controlled human experiments OIH is evident to cold pain, but less consistently found with pain caused by other modalities such as heat, electricity, or pressure. Hyperalgesia detected in response to cold pain can be reduced by the NMDA antagonist ketamine. Patients on methadone maintenance also show an increased sensitivity to nociception between doses. Multi–modal analgesia may be the best strategy fortreatment of OIH in the clinical setting.