Selective targeting of peripheral cannabinoid receptors prevents behavioral symptoms and sensitization of trigeminal neurons in mouse models of migraine and medication overuse headache

Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Toru Yamamoto ◽  
Yatendra Mulpuri ◽  
Mikhail Izraylev ◽  
Qianyi Li ◽  
Menooa Simonian ◽  
...  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Bonnet ◽  
Jizhe Hao ◽  
Nancy Osorio ◽  
Anne Donnet ◽  
Virginie Penalba ◽  
...  

Abstract Medication-overuse headaches (MOH) occur with both over-the-counter and pain-relief medicines, including paracetamol, opioids and combination analgesics. The mechanisms that lead to MOH are still uncertain. Here, we show that abnormal activation of Nav1.9 channels by Nitric Oxide (NO) is responsible for MOH induced by triptan migraine medicine. Deletion of the Scn11a gene in MOH mice abrogates NO-mediated symptoms, including cephalic and extracephalic allodynia, photophobia and phonophobia. NO strongly activates Nav1.9 in dural afferent neurons from MOH but not normal mice. Abnormal activation of Nav1.9 triggers CGRP secretion, causing artery dilatation and degranulation of mast cells. In turn, released mast cell mediators potentiates Nav1.9 in meningeal nociceptors, exacerbating inflammation and pain signal. Analysis of signaling networks indicates that PKA is downregulated in trigeminal neurons from MOH mice, relieving its inhibitory action on NO-Nav1.9 coupling. Thus, anomalous activation of Nav1.9 channels by NO, as a result of chronic medication, promotes MOH.


2018 ◽  
Vol 48 ◽  
pp. 153-159
Author(s):  
Junxia Li ◽  
Chunfu Chen ◽  
Ligong Zhang ◽  
Xiaochen Cui ◽  
Chuanqiao Wei ◽  
...  

Cephalalgia ◽  
2006 ◽  
Vol 26 (5) ◽  
pp. 589-596 ◽  
Author(s):  
G Relja ◽  
A Granato ◽  
A Bratina ◽  
RM Antonello ◽  
M Zorzon

One hundred and one patients suffering from chronic daily headache (CDH) and medication overuse were treated, in an in-patient setting, with abrupt discontinuation of the medication overused, intravenous hydrating, and intravenous administration of benzodiazepines and ademetionine. The mean time to CDH resolution was 8.8 days. The in-patient withdrawal protocol used was effective, safe and well tolerated. There was a trend for a shorter time to CDH resolution in patients who overused triptans ( P = 0.062). There was no correlation between time to CDH resolution and either the type of initial primary headache or duration of medication abuse, whereas time to CDH resolution was related to daily drug intake ( P = 0.01). In multiple regression analysis, daily drug intake, age and type of medication overused were independent predictors of time to CDH resolution. At 3-months' follow-up, no patient had relapsed and was again overusing symptomatic medications.


Cephalalgia ◽  
2006 ◽  
Vol 26 (10) ◽  
pp. 1192-1198 ◽  
Author(s):  
P Zeeberg ◽  
J Olesen ◽  
R Jensen

It is generally accepted that ongoing medication overuse nullifies the effect of prophylactic treatment, although few data support this contention. We set out to describe the treatment outcome in patients withdrawn from medication overuse and relate any improvement to a renewed effect of prophylaxis. For patients with probable medication-overuse headache (pMOH), treated and dismissed from the Danish Headache Centre in 2002 and 2003, we assed, from prospective headache diaries, the headache frequency before and after withdrawal of offending drugs and compared these frequencies with the headache frequency at dismissal. Among 1326 patients, 337 had pMOH. Eligible were 175, mean age 49 years, male/female ratio 1: 2.7. Overall, there was a 46% decrease in headache frequency from the first visit to dismissal ( P < 0.0001). Patients with no improvement 2 months after complete drug withdrawal ( N = 88) subsequently responded to pharmacological and/or non-pharmacological prophylaxis with a 26% decrease in headache frequency as measured from the end of withdrawal to dismissal ( P < 0.0001). At dismissal, 47% were on prophylaxis. Former non-responders to medical prophylaxis had a 49% decrease in headache frequency from first visit to dismissal ( P < 0.0001), whereas those who had never received prophylaxis had a 56% reduction ( P < 0.0001). This difference was not statistically significant ( P = 0.22). Almost all MOH patients benefit from drug withdrawal, either just from the withdrawal or by transformation from therapeutic non-responsiveness to responsiveness. According to the International Classification of Headache Disorders, 2nd edn, the MOH diagnosis requires improvement after drug withdrawal. Our data suggest that these diagnostic criteria are too strict.


Sign in / Sign up

Export Citation Format

Share Document