scholarly journals Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Elisa Bellei ◽  
Emanuela Monari ◽  
Stefania Bergamini ◽  
Aurora Cuoghi ◽  
Aldo Tomasi ◽  
...  
2013 ◽  
Vol 14 (1) ◽  
Author(s):  
Elisa Bellei ◽  
Emanuela Monari ◽  
Aurora Cuoghi ◽  
Stefania Bergamini ◽  
Simona Guerzoni ◽  
...  

Cephalalgia ◽  
2011 ◽  
Vol 31 (12) ◽  
pp. 1282-1290 ◽  
Author(s):  
Antonio Currà ◽  
Gianluca Coppola ◽  
Manuela Gorini ◽  
Elisa Porretta ◽  
Martina Bracaglia ◽  
...  

Background: We investigated whether chronic headache related to medication overuse (MOH) is associated with changes in brain mechanisms regulating inhibitory cortical responses compared with healthy volunteers and episodic migraineurs recorded between attacks, and whether these changes differ according to the drug overused. Subjects and Methods: We studied 40 MOH patients whose symptoms were related to triptans alone, non-steroidal anti-inflammatory drugs (NSAIDs) or both medications combined, 12 migraineurs and 13 healthy volunteers. We used high-intensity transcranial magnetic stimulation over the primary motor cortex to assess the silent period from contracted perioral muscles. Results: In MOH patients the cortical silent period differed according to the type of headache medication overused: in patients overusing triptans alone it was shorter than in healthy volunteers (44.7 ± 14.2 vs. 108.1 ± 30.1 ms), but similar to that reported in migraineurs (59.9 ± 30.4 ms), whereas in patients overusing NSAIDs alone or triptans and NSAIDs combined duration of silent period was within normal limits (80.6 ± 46.4 and 103.8 ± 47.2 ms). Conclusions: Compared with episodic migraineurs, MOH patients overusing triptans have no significant change in cortical inhibition, whereas those overusing NSAIDs have an increase in cortical inhibitory mechanisms. We attribute these changes to medication-induced neural adaptation promoted by changes in central serotonin neurotransmission.


Neurology ◽  
2017 ◽  
Vol 89 (12) ◽  
pp. 1296-1304 ◽  
Author(s):  
Ann I. Scher ◽  
Paul B. Rizzoli ◽  
Elizabeth W. Loder

It is a widely accepted idea that medications taken to relieve acute headache pain can paradoxically worsen headache if used too often. This type of secondary headache is referred to as medication overuse headache (MOH); previously used terms include rebound headache and drug-induced headache. In the absence of consensus about the duration of use, amount, and type of medication needed to cause MOH, the default position is conservative. A common recommendation is to limit treatment to no more than 10 or 15 days per month (depending on medication type) to prevent headache frequency progression. Medication withdrawal is often recommended as a first step in treatment of patients with very frequent headaches. Existing evidence, however, does not provide a strong basis for such causal claims about the relationship between medication use and frequent headache. Observational studies linking treatment patterns with headache frequency are by their nature confounded by indication. Medication withdrawal studies have mostly been uncontrolled and often have high dropout rates. Evaluation of this evidence suggests that only a minority of patients required to limit the use of symptomatic medication may benefit from treatment limitation. Similarly, only a minority of patients deemed to be overusing medications may benefit from withdrawal. These findings raise serious questions about the value of withholding or withdrawing symptom-relieving medications from people with frequent headaches solely to prevent or treat MOH. The benefits of doing so are smaller, and the harms larger, than currently recognized. The concept of MOH should be viewed with more skepticism. Until the evidence is better, we should avoid dogmatism about the use of symptomatic medication. Frequent use of symptom-relieving headache medications should be viewed more neutrally, as an indicator of poorly controlled headaches, and not invariably a cause.


2013 ◽  
Vol 3 (2) ◽  
pp. 94-98
Author(s):  
A Rahman ◽  
R Habib ◽  
NB Bhowmik ◽  
A Haque

Medication Overuse Headache (MOH) was previously termed analgesic rebound headache, drug-induced headache, and medication-misuse headache. It is not a primary headache but frequently coexists with primary chronic daily headache. All acute symptomatic medications used to treat headaches have the potential for causing MOH. Highest with opioids, butalbital-containing combination analgesics, and aspirin/ acetaminophen/caffeine combinations. The development is typically preceded by an episodic headache disorder, usually migraine or tension-type headache, that has been treated with frequent and excessive amounts of acute symptomatic medications. The diagnosis is based upon clinical impression. A history of analgesic use averaging more than two to three days per week in association with chronic daily headache is suggestive. The diagnosis is made when the pattern of frequent headaches fulfills the diagnostic criteria for MOH. The basic steps in the management: Patient education, withdrawal of the offending medication, bridge (transitional) therapy, establishment of a headache treatment regimen covering acute and preventive care, follow up and relapse prevention. Birdem Med J 2013; 3(2): 94-98 DOI: http://dx.doi.org/10.3329/birdem.v3i2.17213


Cephalalgia ◽  
2020 ◽  
Vol 40 (9) ◽  
pp. 903-912 ◽  
Author(s):  
Jill C Rau ◽  
Edita Navratilova ◽  
Janice Oyarzo ◽  
Kirk W Johnson ◽  
Sheena K Aurora ◽  
...  

Background Medication overuse is a significant issue that complicates the treatment of headache disorders. The most effective medications for the acute treatment of migraine all have the capacity to induce medication overuse headache (MOH). Novel acute migraine-specific treatments are being developed. However, because the mechanism(s) underlying medication overuse headache are not well understood, it is difficult to predict whether any particular acute medication will induce MOH in susceptible individuals. LY573144 (lasmiditan), a 5-HT1F receptor agonist, has recently been shown to be effective in the acute treatment of migraine in phase 3 trials. The aim of this study is to determine whether frequent administration of lasmiditan induces behaviors consistent with MOH in a pre-clinical rat model. Methods Sprague Dawley rats were administered six doses of lasmiditan (10 mg/kg), sumatriptan (10 mg/kg), or sterile water orally over 2 weeks and cutaneous allodynia was evaluated regularly in the periorbital and hindpaw regions using von Frey filaments. Testing continued until mechanosensitivity returned to baseline levels. Rats were then submitted to bright light stress (BLS) or nitric oxide (NO) donor administration and were again evaluated for cutaneous allodynia in the periorbital and hindpaw regions hourly for 5 hours. Results Both lasmiditan and sumatriptan exhibited comparable levels of drug-induced cutaneous allodynia in both the periorbital and hindpaw regions, which resolved after cessation of drug administration. Both lasmiditan and sumatriptan pre-treatment resulted in cutaneous allodynia that was evoked by either BLS or NO donor. Conclusions In a pre-clinical rat model of MOH, oral lasmiditan, like sumatriptan, induced acute transient cutaneous allodynia in the periorbital and hindpaw regions that after resolution could be re-evoked by putative migraine triggers. These results suggest that lasmiditan has the capacity to induce MOH through persistent latent peripheral and central sensitization mechanisms.


2020 ◽  
pp. 109158182096151
Author(s):  
Jennifer C. Shing ◽  
Kai Schaefer ◽  
Shaun E. Grosskurth ◽  
Andy H. Vo ◽  
Tatiana Sharapova ◽  
...  

Predictive indicators of testicular toxicity could improve drug development by allowing early in-life screening for this adverse effect before it becomes severe. We hypothesized that circulating microRNAs (miRNAs) could serve as testicular toxicity biomarkers in dogs. Herein, we describe the results of an exploratory study conducted to discover biomarkers of drug-induced testicular injury. Following a dose-selection study using the testicular toxicant ethylene glycol monomethyl ether (EGME), we chose a dose of 50 mg/kg/d EGME to avoid systemic toxicity and treated 2 groups of dogs (castrated, non-castrated) for 14 to 28 days. Castrated animals were used as negative controls to identify biomarkers specific for testicular toxicity because EGME can cause toxicity to organ systems in addition to the testis. Blood was collected daily during the dosing period, followed by recovery for 29 to 43 days with less frequent sampling. Dosing was well tolerated, resulting in mild-to-moderate degeneration in testes and epididymides. Global profiling of serum miRNAs at selected dosing and recovery time points was completed by small RNA sequencing. Bioinformatics data analysis using linear modeling demonstrated several circulating miRNAs that were differentially abundant during the dosing period compared with baseline and/or castrated control samples. Confirmatory reverse transcription quantitative polymerase chain reaction data in these animals was unable to detect sustained alterations of miRNAs in serum, except for 1 potential candidate cfa-miR-146b. Taken together, we report the results of a comprehensive exploratory study and suggest future directions for follow-up research to address the challenge of developing diagnostic biomarkers of testicular toxicity.


Sign in / Sign up

Export Citation Format

Share Document