Medication-overuse headache and opioid-induced hyperalgesia: A review of mechanisms, a neuroimmune hypothesis and a novel approach to treatment

Abstract

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Too Much of a Good Thing

“…One explanation for this is the phenomenon known as opioid-induced hyperalgesia (OIH) À the paradoxical worsening of pain with continuing or increasing opiate usage. 23 Many of the features seen in OIH are also observed in MOH. In both cases, the increasing pain involves upregulation of CGRP and the hyperexcitability of dorsal horn neurons.…”

Headache of Analgesic Abuse as a Cause of New Pain Pathways Development

“…Of note, opioids have been found to be one of the most problematic drugs found to induce chronic headache, regardless of the purpose of their use whether it be chronic headache or any other chronic pain condition such as back pain, oncologic pain, and so on. The underlying mechanism seems to be "the activation of toll-like receptor-4 on glial cells, resulting in a pro-inflammatory state that manifests clinically as increased pain" [101], such activation may explain not only the development of MOH but also of the transformation to migraine [102]. But opiates are not the only molecules associated with MOH, there is also strong evidence suggesting that combined analgesics as well as joined ergotamine-caffeine preparations may induce a metabolic decrease in several brain areas, especially the orbitofrontal cortex leading to a decrease in intrinsic pain downregulation circuits and the development of chronic headaches such as MOH and modified migraine (MM) [105].…”

Medication overuse and chronic migraine: a critical review according to clinical pharmacology

“…MOH caused by opioids could be similar to hyperalgesia observed in animals. It seems to derive from the activation of glial cells by opioids, with the release of proinflammatory cytokines and an increased activity of excitatory neurotransmitters [64]. Acetaminophen overuse could induce MOH, altering cortical excitability and leading to an increased susceptibility of cortical spreading depression [65].…”