Single and double pain responses to individually titrated ultra-short laser stimulation in humans

Abstract

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.

Randomized cross-over evaluation of investigator gender on pain thresholds in healthy volunteers

“…However, since those investigators were dressed to emphasize their gender roles, those results were interpreted to primarily reflect influence of traditional gender role expectations, as also proposed in a survey of epidemiological and laboratory data on sex differences in pain perception [ 29 ]. Nevertheless, another study from the mid-2000s and a recent study, both based on heat-induced pain, not emphasizing traditional investigator gender roles in line with our study, have also reported higher pain thresholds in males evaluated by a neutrally dressed female [ 5 ], [ 6 ], representing more realistic clinical patient-physician interaction.…”

“…Advantages of this study are the blinding of participants to the main study purpose (to avoid some psychosocial impact on pain perception) and of both participants and investigators to on-line EPT levels. The use of a valid and reliable [ 42 ], [ 43 ] investigator-independent stimulation device designed for this specific purpose instead of investigator-dependent ones [ 4 ], [ 5 ], [ 6 ], [ 7 ] is considered to be another advantage. Combining EPT determination with individual VAS scoring – considered as the gold standard for pain assessment [ 44 ] – empowers our findings.…”

“…Evaluations by female investigators have been associated with higher thresholds of pain induced by mechanical pressure [ 4 ] or laser [ 5 ] stimulation, and with lower intensity of pain induced by heat [ 6 ] or cold [ 7 ] stimulation in study participants. However, female investigators have also been reported to obtain similar levels of pain threshold, but lower levels of pain tolerance to cold-induced nociceptive stimulation [ 8 ].…”

“…Numerous original studies on subject gender with different pain stimuli have found lower pain threshold levels [ 8 ], [ 10 ], [ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ], [ 19 ], [ 20 ] or higher pain intensity levels [ 7 ], [ 21 ], [ 22 ], [ 23 ] in females – recently confirmed in two reviews [ 1 ], [ 24 ], possibly reflecting physiological sex differences [ 21 ] or psychosocial factors [ 25 ] like gender-role expectations [ 26 ], [ 27 ] – whereas others have found no differences [ 5 ], [ 9 ], [ 13 ], [ 27 ], [ 28 ].…”

“…Based on available data in females and males evaluated by investigators of both genders [ 4 ], [ 5 ], [ 7 ], [ 17 ], [ 23 ], our main study hypothesis was that evaluations by female investigators result in higher pain threshold levels and/or lower pain intensity levels than evaluations by male investigators. Our second study hypothesis was that females have lower pain threshold levels and/or report higher pain intensity levels than males regardless of investigator gender.…”