How to make calibration less painful – a proposition of an automatic, reliable and time-efficient procedure

Background In neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli that have different modalities. However, such studies often lack calibration procedure implementation, have a vague protocol description, do not provide data quality quantification, or even omit required control for gender pain differences. All this hampers not only study repetition but also interexperimental comparisons. Moreover, typical calibration procedures are long and require a high number of stimulations which may cause participants’ discomfort and stimuli habituation. Method To overcome those shortcomings, we present an automatic staircase pain calibration method for A-delta-specific electrical stimulation adjusted to the magnetoencephalography environment. We provide an in-depth data analysis of the collected self-reports from seventy healthy volunteers (37 males) and propose a method based on a dynamic truncated linear regression model (tLRM). We compare its estimates for the sensation ( t ), and pain ( T ) thresholds, as well as for the mid-pain stimulation ( MP ), with those calculated using a traditional threshold method and standard linear regression models. Results Compared to the other threshold methods, tLRM exhibits higher R2 and requires 36% fewer stimuli application and has significantly higher t and lower T and MP intensities. Regarding sex differences, both lower t and T were found for females compared to males, regardless of the calibration method. Conclusions The proposed tLRM method quantifies the quality of the calibration procedure, minimizes its duration and invasiveness, as well as provides validation of linearity between stimuli intensity and subjective scores, making it an enabling technique for further studies. Moreover, our results highlight the importance of control for gender in pain studies. Summary The purpose of this study was to shorten and automatize the calibration method which is an enabling technique for realizing neurophysiological studies on pain. The proposed method is based on a dynamic truncated linear regression model and was shown to require 36% fewer stimuli application compared to the traditional staircase method. Furthermore, the calibration was adjusted to A-delta specific intraepidermal electrical stimulation, quantifies the quality of the resulting calibration parameters and provides a validation of linearity between stimuli intensity and subjective scores. The results also highlight the importance of control for participant gender in studies where different types of stimulation are used to induce pain sensation. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by H2020 EU-funded Marie Skłodowska-Curie Individual Fellowship (MSCA-IF), Grant agreement ID: 896262. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The calibration procedure design was approved by the Ethics Committee of the Universidad Complutense de Madrid (UCM), the Universidad Politécnica de Madrid (UPM), and the Basque Centre on Cognition, Brain and Language (BCBL), and followed the Helsinki Declaration and national and European Union regulations as part of a the MSCA project. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors