Electroacupuncture decreases inflammatory pain through a pro-resolving mechanism involving the peripheral annexin A1-formyl peptide receptor 2/ALX-opioid receptor pathway.

The pro-resolving mechanism is a recently described endogenous process that controls inflammation. The present study evaluated components of this mechanism, including annexin 1 (ANXA1) and the formyl peptide receptor 2/ALX (FPR2/ALX) receptor, in the antihyperalgesic effect induced by electroacupuncture (EA) in an animal model of persistent peripheral inflammation. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2-10 Hz, ST36-SP6) or subcutaneous BML-111 injection (FPR2/ALX agonist) for 5 consecutive days. In a separate set of experiments, on the first and fifth days after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or naloxone (non-selective opioid receptor antagonist) before EA or BML-111 injection. Paw protein levels of FPR2/ALX and ANXA1 were evaluated on the second day after CFA injection by western blotting technique. EA and BML-111 reduced mechanical hyperalgesia. I.pl. naloxone or WRW4 prevented the antihyperalgesic effect induced by either EA or BML-111. EA increased ANXA1 but did not alter FPR2/ALX receptor levels in the paw. Furthermore, i.pl. pretreatment with WRW4 prevented the increase of ANXA1 levels induced by EA. This work demonstrates that the EA antihyperalgesic effect on inflammatory pain involves the ANXA1/FPR2/ALX pro-resolution pathway. This effect appears to be triggered by the activation of FPR2/ALX receptors and crosstalk communication with the opioid system.

Eluxadoline en el tratamiento del síndrome de intestino irritable con predominio de diarrea. Punto de vista SEPD / Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome. The SEPD perspective

Los trastornos funcionales del tubo digestivo, entre los que se encuentra el síndrome de intestino irritable con predominio de diarrea, constituyen una patología muy prevalente en todo el mundo, con un gran impacto tanto económico como en la calidad de vida de los pacientes, que no cuenta con alternativas terapéuticas completamente satisfactorias. Estas circunstancias han propiciado la investigación de diferentes moléculas con unas dianas terapéuticas más específicas como los receptores opioides. Eluxadoline (Vibercy(R) en Estados Unidos/Truberzi® en Europa, de Allergan) es una molécula agonista con efectos locales mixtos tanto agonista de los receptores opioides μ- y κ- como antagonista del receptor δ-opioide, que fue aprobada en 2015 por la Food and Drug Administration (FDA) y en 2016 por la Agencia Europea del Medicamento (EMA) para su indicación en el síndrome de intestino irritable con predominio de diarrea. Eluxadoline es un fármaco que ofrece, con ventaja sobre los que se utilizan en esta patología, el control tanto de la consistencia de las deposiciones como del dolor abdominal, con una buena tolerancia en la mayoría de los casos y una mejoría en la calidad de vida de estos pacientes, por lo que es una molécula a considerar en el abordaje de esta patología. Como en todo producto de reciente incorporación terapéutica, es de esperar una farmacovigilancia adecuada así como que se vaya generando conocimiento de estudios que nos ofrezcan información sobre diferentes escenarios tales como el tratamiento a demanda, la valoración de la pérdida de respuesta, la utilización del tratamiento como rescate a otras moléculas y la valoración del coste-eficacia del fármaco, para caracterizar y posicionar de una manera más precisa eluxadoline dentro del espectro terapéutico (AU)

Functional gut disorders, including diarrhea-predominant irritable bowel syndrome, are highly prevalent conditions worldwide that significantly impact health economy and patient quality of life, yet lacking fully satisfactory therapeutic options. These circumstances fostered research on various molecules with more specific therapeutic targets, including opioid receptors. Eluxadoline (Allergan’s Vibercy® in the USA, Truberzi® in Europe) is a locally-acting mixed mu- and kappa-opioid receptor agonist, and delta-opioid receptor antagonist, that was licensed in 2015 by the Food and Drug Administration (FDA) and in 2016 by the European Medicines Agency (EMA) for use in diarrhea-predominant irritable bowel syndrome. Eluxadoline provides, with advantage over the current standard of care, control of both stool consistency and abdominal pain, good tolerability in most cases, and improved quality of life, hence it deserves consideration when approaching a patient with this disorder. As with any recently approved therapy, adequate pharmacovigilance is to be expected, as well as studies to inform on different scenarios such as on-demand therapy, loss of response assessment, use as rescue therapy for other molecules, and cost-effectiveness, to further characterize and more accurately position eluxadoline within the therapeutic spectrum (AU)

Síndrome de la bolsa de orina púrpura / Purple urine bag syndrome

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