​​Uncovering Novel Mechanisms Driving Opioid-Induced Hyperalgesia

Exploring the pain paradox of opioid-induced hyperalgesia

Abstract

Amidst the synthetic opioid epidemic of the early 2000s emerged a lesser-known side effect, opioid-induced hyperalgesia (OIH). Opioids are medicinally used to attenuate pain. However, OIH is the paradoxical effect of an individual consuming opioids and instead experiencing increased sensitivity to certain painful stimuli. OIH is understudied and its prevalence remains unknown. In effort to determine possible causes and explanations for OIH, a comprehensive literature review was conducted. This review identified relationships among OIH, glial cell activation, neuropeptides, and the dorsal root ganglion, a hub of sensory neurons at the top of the spinal cord. Glial cells in the dorsal root ganglion activate in response to the stress of being under opioid influence. Glial cell activation then leads to the dysregulation of nociceptive neuropeptides in the dorsal root ganglion that contribute to an increased perception of pain. The findings demonstrate a mechanism by which neuropeptides and glial cells interact and contribute to pain development. This mechanism provides potential therapeutic targets for OIH, other forms of hyperalgesia conditions, and chronic pain management strategies. Future research should focus on exploring these pathways in detail to develop novel, non-opioid pain treatments that eliminate the devastating effects of OIH.