Involvement of Pro‐Nociceptive 5‐HT_2A Receptor in the Pathogenesis of Medication‐Overuse Headache

Abstract

These findings suggest that up-regulation of pro-nociceptive 5-HT(2A) receptor is an important step in the process of cortical hyper-excitation and nociceptive facilitation induced by chronic analgesic exposure.

Original article. Potential risk of dihydroergotamine causing medicationoveruse headache: preclinical evidence

“…Our previous experiments using immunohistochemistry show that the majority of neurons in this area that express c-Fos after CSD were confined to the superficial laminae especially the TNC, an important nucleus controlling cranial nociception [8,9]. The finding of a decrease in c-Fos expression in this area can be interpreted as a decrease in trigeminal activation and therefore nociception.…”

“…First, topical application of KCl is a robust method for CSD induction where a threshold of cortical susceptibility is not assessed. Nevertheless, it is a standard protocol for inducing repetitive CSDs to evaluate the level of cortical excitability that we have used in the previous studies [8,9,11]. Second, we attempted to quantitate total c-Fos expression in the TNC by western blotting analysis.…”

“…We designed experiments according to our previous studies of chronic analgesic exposure. In those studies, we showed that animals with prolonged analgesic exposure demonstrated an increased susceptibility to develop cortical spreading depression (CSD), an electrophysiological phenomenon analogous to the aura phase of migraine [8,9]. CSD activates the trigeminovascular system, including the large cranial vessels, proximal intracranial vessels, and the dura mater that are innervated by branches of the ophthalmic division of the trigeminal nerve [10].…”

Too Much of a Good Thing

“…Chronic acetaminophen use upregulates cerebral cortex pronociceptive 5-HT2A receptors. 22 Continual use of opiates is frequently associated with increased pain. 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.…”

Medication Overuse Headache: Practical Guidelines

“…Установлено, что длительное использование ацетаминофена снижает порог корковой распространя-ющейся депрессии (КРД), увеличивает частоту КРД и экспрессию с-Fos в корковых нейронах, а также наруша-ет активность тригеминальной ноцицептивной системы. Корковая и тригеминальная сенситизация развивается одновременно с увеличением экспрессии рецепторов 5-НТ2А [17,18]. На основании данных фМРТ показано, что при ЛИГБ экспрессия серотониновых рецепторов преобладает в орбитофронтальной, медиальной нижней фронтальной, первичной сенсомоторной, задней цингу-лярной областях, что еще раз подчеркивает роль пове-денческих и личностных факторов в злоупотреблении анальгетиками [17].…”