Instrumentation issues in implementation science

Background Like many new fields, implementation science has become vulnerable to instrumentation issues that potentially threaten the strength of the developing knowledge base. For instance, many implementation studies report findings based on instruments that do not have established psychometric properties. This article aims to review six pressing instrumentation issues, discuss the impact of these issues on the field, and provide practical recommendations. Discussion This debate centers on the impact of the following instrumentation issues: use of frameworks, theories, and models; role of psychometric properties; use of ‘home-grown’ and adapted instruments; choosing the most appropriate evaluation method and approach; practicality; and need for decision-making tools. Practical recommendations include: use of consensus definitions for key implementation constructs; reporting standards (e.g., regarding psychometrics, instrument adaptation); when to use multiple forms of observation and mixed methods; and accessing instrument repositories and decision aid tools. Summary This debate provides an overview of six key instrumentation issues and offers several courses of action to limit the impact of these issues on the field. With careful attention to these issues, the field of implementation science can potentially move forward at the rapid pace that is respectfully demanded by community stakeholders

Kappa opioid receptor antagonists: A possible new class of therapeutics for migraine prevention.

Background: Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods: Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine. Nor-binaltorphimine (nor-BNI), a long-acting KOR antagonist or CYM51317, a novel short-acting KOR antagonist, were given systemically either during sumatriptan priming or immediately before environmental stress challenge. The effects of KOR blockade in the amygdala on stress-induced allodynia was determined by administration of nor-BNI into the right or left central nucleus of the amygdala (CeA). Results: KOR blockade prevented both stress-induced allodynia and increased plasma CGRP. Stress increased dynorphin content and phosphorylated KOR in both the left and right CeA in sumatriptan-primed rats. However, KOR blockade only in the right CeA prevented stress-induced cephalic allodynia as well as extracephalic allodynia, measured in either the right or left hindpaws. U69,593, a KOR agonist, given into the right, but not the left, CeA, produced allodynia selectively in sumatriptan-primed rats. Both stress and U69,593-induced allodynia were prevented by right CeA U0126, a mitogen-activated protein kinase inhibitor, presumably acting downstream of KOR. Conclusions: Our data reveal a novel lateralized KOR circuit that mediated stress-induced cutaneous allodynia and increased plasma CGRP in an injury-free model of functional cephalic pain with features of migraine and medication overuse headache. Selective, small molecule, orally available, and reversible KOR antagonists are currently in development and may represent a novel class of preventive therapeutics for migraine