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

Bellei, Elisa; Monari, Emanuela; Bergamini, Stefania; Cuoghi, Aurora; Tomasi, Aldo; Guerzoni, Simona; Ciccarese, Michela; Pini, Luigi Alberto

doi:10.1186/s10194-015-0559-8

Cited by 16 publications

(24 citation statements)

References 47 publications

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“…Ptgds converts PGH 2 to PGD 2 , which is one of the most abundant prostaglandins in the brain (41,42,82). PGD 2 is known to have important roles in the regulation of nociception (43,83), temperature (53) and sleep (52). There is also evidence that Ptgds is involved in the transport of retinoids in the brain (84), thus playing essential roles in the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Tavares‐Ferreira

Ray

Sankaranarayanan

et al. 2020

Preprint

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Background: There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences. Methods: We used Translating Ribosome Affinity Purification (TRAP) sequencing and behavioral pharmacology to test the hypothesis that nociceptor (Nav1.8 expressing neurons) translatomes would differ by sex. Results: We found 66 genes whose mRNA were sex-differentially bound to nociceptor ribosomes. Many of these genes have known neuronal functions but have not been explored in sex differences in pain. We focused on Ptgds, which was increased in female mice. The mRNA encodes the prostaglandin D2 (PGD2) synthesizing enzyme. We observed increased Ptgds protein and PGD2 in female mouse DRG. The Ptgds inhibitor AT-56 caused intense pain behaviors in male mice but was only effective at high doses in females. Conversely, female mice responded more robustly to another major prostaglandin, PGE2, than did male mice. Ptgds protein expression was also higher in female cortical neurons, suggesting DRG findings may be generalizable to other nervous system structures. Conclusions: Nociceptor TRAP sequencing (TRAP-seq) reveals unexpected sex differences in one of the oldest known nociceptive signaling molecule families, the prostaglandins. Our results demonstrate that translatome analysis reveals physiologically relevant sex differences important for fundamental protective behaviors driven by nociceptors.

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Section: Discussionmentioning

confidence: 99%

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Tavares‐Ferreira

Ray

Sankaranarayanan

et al. 2020

Preprint

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“…Migraine is an episodic disorder, but in its natural course, its frequency, in a particular subset of patients, could progressively increase and evolve to a chronic form. The higher frequency of attacks can lead to a chronic intake of abortive medications as triptans and non-steroidal anti-inflammatory drugs (NSAIDs), both associated with a greater risk of developing cardio-cerebrovascular events and renal events [ 26 , 27 ]. Thus, CM is a serious and debilitating neurological disorder with high risk of medication overuse given by the frequent partial response to treatment, both abortive and preventive.…”

Section: Discussionmentioning

confidence: 99%

Quarterly repeat cycles of onabotulinumtoxinA in chronic migraine patients: the benefits of the prolonged treatment on the continuous responders and quality-of-life conversion rate in a real-life setting

et al. 2017

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OnabotulinumtoxinA was approved for treatment of chronic migraine (CM) after publication of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) trials. However, the PREEMPT trials lasted only up to 1 year. The main aim of our retrospective study was to evaluate whether a prolonged treatment of onabotulinumtoxinA (18 months, six quarterly cycles) will sustain or further improve the efficacy results and the quality of life achieved at 6 and 12 months. Patients were adults with CM with or without overuse of drugs, with at least six regularly repeat onabotulinumtoxinA treatments, administered according to the PREEMPT protocol. The outcomes were investigated after 6, 12, and 18 months of treatment with respect to baseline and with respect to each previous study time point. Headache days and hours, and dosage of headache medication taken with latency period, were collected from the patients daily. Quality of life was evaluated by means of the Migraine Disability Assessment (MIDAS) questionnaire. At each study time point, the proportion of responder patients with respect to baseline was evaluated. For all measures, the baseline data were referred to the previous month before starting. Forty-seven patients were evaluated. Our data show a decrease in the monthly headache days and hours, at each study evaluation, with respect to the previous one. They showed that beyond the first year, a statistically significant difference in the monthly days of headache compared at 18 vs. 12 months is observed. A significantly higher proportion of patients (with a response greater than 75% decrease from baseline in the frequency of headache days and hours) was observed at month 18 compared to month 12. The proportion of patients in MIDAS grade I increased over time, and a statistically significant improvement in MIDAS I score was obtained from month 12 to month 18. A positive modification in the consumption of analgesics over time was observed (p for trend <0.001). The mean acute drug latency strongly decreased over time. Our study confirmed that onabotulinumtoxinA is an effective treatment to reduce headache-related disability and improve patients’ quality of life, highlighting that upon repeated administration, the therapy efficacy increases significantly and a progressive trend of “first-time response” is observed for the entire period under consideration.

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“…The higher frequency of attacks can lead to a chronic intake of abortive medications as triptans and non-steroidal anti-inflammatory drugs (NSAIDs), both associated with a greater risk of developing cardio-cerebrovascular events and renal damages [2,3].…”

Section: Introductionmentioning

confidence: 99%

Chronic migraine treatment: from OnabotulinumtoxinA onwards

Negro

Curto

Lionetto

et al. 2016

Expert Review of Neurotherapeutics

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Our goal is to review the existing data on OnabotulinoumtoxinA and CGRP-targeting drugs such as anti-CGRP monoclonal antibodies, one of the most promising migraine drugs under development. The research of bibliographic databases has included only published peer-reviewed articles from indexed journals. Expert commentary: To date, real-life studies are supporting OnabotulinumtoxinA in the treatment of chronic migraine. Additionally, anti-CGRP mAbs showed good efficacy and safety in recent RCTs and may soon contribute to improve the quality of life of patients suffering with migraine.

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

Cited by 16 publications

References 47 publications

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Quarterly repeat cycles of onabotulinumtoxinA in chronic migraine patients: the benefits of the prolonged treatment on the continuous responders and quality-of-life conversion rate in a real-life setting

Chronic migraine treatment: from OnabotulinumtoxinA onwards

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