Acute Reduction of Anandamide-Hydrolase (FAAH) Activity is Coupled With a Reduction of Nociceptive Pathways Facilitation in Medication-Overuse Headache Subjects After Withdrawal Treatment.

Abstract

“Objectives.- We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication-overuse headache, and (2) the effect of withdrawal treatment on both. Background.- The endocannabinoid system antinociception effect includes prevention of nociceptive pathways sensitization. The sensitization of the pain pathways has been demonstrated to be pivotal in the development and maintenance of chronic form of migraine, including medication-overuse headache. Methods.- We used the temporal summation threshold of the nociceptive withdrawal reflex to explore the spinal cord pain processing, and the platelet activity of the enzyme fatty acid amide hydrolase to detect the functional state of the endocannabinoid system in 27 medication-overuse headache subjects before and 10 and 60 days after a standard withdrawal treatment and compared results with those of 14 controls. Results.- A significantly reduced temporal summation threshold and increased related pain sensation was found in subjects before withdrawal treatment when compared with controls. A significant fatty acid amide hydrolase activity reduction coupled with a significant improvement (reduction) in facilitation of spinal cord pain processing (increase in temporal summation threshold and reduction in related pain sensation) was found in medication-overuse headache subjects at both 10 and 60 days after withdrawal treatment when compared with medication-overuse headache subjects before withdrawal treatment. Conclusions.- We demonstrated a marked facilitation in spinal cord pain processing in medication-overuse headache before withdrawal treatment when compared with controls. Furthermore, the acute reduction of the fatty acid amide hydrolase activity coupled with a reduction of the facilitation in pain processing immediately (10 days) after withdrawal treatment and its persistence 60 days after withdrawal treatment could represent the consequence of a mechanism devoted to acutely reduce the degradation of endocannabinoids and aimed to increase the activity of the endocannabinoid system that results in an antinociceptive effect.”

http://www.ncbi.nlm.nih.gov/pubmed/22670561

Degradation of endocannabinoids in chronic migraine and medication overuse headache.

Abstract

“Chronic migraine (CM) is frequently associated with medication overuse headache (MOH). The endocannabinoid system plays a role in modulating pain including headache and is involved in the common neurobiological mechanism underlying drug addiction and reward system. Anandamide (AEA) and 2-arachidonoylglycerol are the most biologically active endocannabinoids, which bind to both central and peripheral cannabinoid receptors. The level of AEA in the extracellular space is controlled by cellular uptake via a specific AEA membrane transporter (AMT), followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid amide hydrolase, FAAH). AMT and FAAH have also been characterized in human platelets. We assayed the activity of AMT and of FAAH in platelets isolated from four groups of subjects: MOH, CM without MOH, episodic migraine and controls. AMT and FAAH were significantly reduced in CM and MOH, compared to either controls or episodic migraine group. This latter finding was observed in both males and females with CM and MOH. Changes observed in the biochemical mechanisms degrading endogenous cannabinoids may reflect an adaptative behaviour induced by chronic headache and/or drug overuse.”

http://www.ncbi.nlm.nih.gov/pubmed/18358734