ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Background This preclinical study in humans was designed to selectively induce delayed nociceptive pain responses to individually titrated laser stimulation, enabling separate bedside intensity scoring of both immediate and delayed pain. Methods Forty-four (fourteen female) healthy volunteers were subjected to repeated nociceptive dermal stimulation in the plantar arc, based on ultra-short carbon dioxide laser with individually titrated energy levels associated with mild pain. Results Data was analysed in 42 (12 female) subjects, and 29 of them (11 females) consistently reported immediate and delayed pain responses at second-long intervals to each nociceptive stimulus. All single pain responses were delayed and associated with lower levels ( p = 0.003) of laser energy density (median 61; IQR 54–71 mJ/mm 2 ), compared with double pain responses (88; 64–110 mJ/mm 2 ). Pain intensity levels associated with either kind of response were readily assessable at bedside. Conclusions This study is the first one to show in humans that individually titrated ultra-short pulses of laser stimulation, enabling separate pain intensity scoring of immediate and delayed responses at bedside, can be used to selectively induce and evaluate delayed nociceptive pain, most likely reflecting C-fibre-mediated transmission. These findings might facilitate future research on perception and management of C-fibre-mediated pain in humans.

Background Postoperative pain is common but often difficult to assess, and there are many potential confounders. Over the last decades, the gender of investigator as well as participant has been found to influence pain perception in both preclinical and clinical studies. However, to our knowledge this has not been studied in various postoperative patients. Objectives of this study were to test the hypotheses that pain intensity levels early after acute or scheduled in- or out-hospital surgery are lower when evaluated by a female investigator, and higher when reported by a female patient. Methods In this prospective observational paired crossover study, two investigators of opposite genders independently obtained individually reported pain intensity levels with a visual analogue scale in a mixed cohort of adult postoperative study patients at Skåne University Hospital in Malmö, Sweden. Results In total, 245 (129 female) study patients were included and then one female excluded. The study patients rated their intensity of postoperative pain lower when evaluated by a female than by a male investigator (P = 0.006), where the male patients constituted the significant difference (P < 0.001). Pain intensity levels did not differ between female and male study patients (P = 0.210). Conclusions Main findings of lower pain intensity reported by males to a female than to a male investigator early after surgery in this paired crossover study in mixed postoperative patients, indicate that potential impact of investigator gender on pain perception should be considered and further evaluated in clinical bedside practice. Trial registration Retrospectively registered in the ClinicalTrials.gov research database on 24th June 2019 with TRN number NCT03968497.

Background and aims: This randomized cross-over study in healthy volunteers was designed primarily to evaluate the potential impact of investigator gender on electrical pain threshold (EPT) and corresponding pain intensity levels, and secondly to evaluate potential differences in those interventions between female and male study participants. Methods: Forty adult volunteers (22 females) were included. An electrical stimulation device was used to determine EPT levels (in pain magnitude scores) in series of three in each study participant – once by a female, and once by a male investigator – according to a predefined cross-over design schedule. Corresponding levels of pain intensity were scored on a visual analog scale (VAS) slide ruler. Results: Study data was obtained and analysed in all participants. Significantly higher EPT levels were determined by the female investigator compared with the male investigator (median 22 (IQR 12–31) vs. 8 (6–10) pain magnitude scores; p <0.0001), despite similar levels of reported pain intensity (1.9 (1.2–3.0) vs. 2.0 (1.1–3.4) VAS units; p >0.300). There were no differences in EPT levels between female and male subjects evaluated by female ( p >0.300) and male ( p =0.125) investigators, or between the first and second series of stimulation ( p >0.300). Conclusions: Our finding of significantly higher EPT levels when study participants of both genders – despite no difference in reported pain intensity – were evaluated by a female than by a male investigator, indicates a potential impact of investigator gender on the individual perception of pain. Implications: By contributing to a better understanding of how individual pain threshold levels are potentially influenced by investigator gender, this study might facilitate future evaluation of pain conditions in both preclinical and clinical settings.