Study protocol for microneurographic investigation of nociceptor sensitisation in Fibromyalgia Syndrome. (MICRO-FMS)

IntroductionChronic pain in fibromyalgia may be driven by abnormal ongoing activity in a subclass of C-fibre nociceptors known as Type1B or CMi nociceptors. As is common in C-nociceptor microneurography studies, the modest patient numbers in these prior studies generate large confidence intervals around the point estimate of the prevalence of this abnormal activity. This complicates the interpretation of the relative importance of this ongoing nociceptor activity as a pain generating mechanism in fibromyalgia. The study aims to improve precision via an adaptive Bayesian protocol that maximises the yield and quality of data collection whilst minimising patient burden. MethodsThe study employs an optimised microneurography protocol with an adaptive study design. The microneurography protocol incorporates early identification of CMi nociceptors via an abbreviated activity dependent slowing protocol to increase yields enabling efficient collection of the primary outcome data. The adaptive study design will use Bayesian principles to iteratively assess the predictive probability of futility, and terminate early if there is high confidence that the hypothesis is false. Furthermore, the study will employ questionnaires to explore links with pain in the area under study to the electrophysiology data. Finally, quantitative sensory testing will be used to investigate whether the irritable nociceptor phenotype is associated with abnormalities in CMi nociceptor physiology. Ethics & DisseminationThis study has received HRA REC approval in the UK. Participants will provide written informed consent, and may withdraw at any time without consequence. At the end of the study, the results will be disseminated through peer-reviewed publication, and the data made available via a data repository. Strengths & limitations of this studyBayesian predictive probability of futility to minimise patient burden in microneurography Microneurography for objective interrogation of the peripheral nervous system Optimised microneurography protocol to efficiently answer primary hypotheses Subjective elements of early termination criteria of the study assessed and co-developed with Patient and Public Inclusion and Engagement Group