Pain modulation induced by Heterotopic Noxious Counter-Stimulation (HNCS) : psychophysiological assessment of adequate stimulation paradigms and sex-related effects

Field: Neuroscience (Life Sciences)

This work comprises three studies whose main concern was to find a valid tonic pain model able to trigger a genuine diffuse noxious pain inhibition. All studies were performed in healthy, drug-free volunteers and whereas the first two are validation studies, the third is an application study of the previous two. The aim of the first study was to characterize the cold pressor (CPT) and hot water immersion test (HIT) from a physiological and a psychophysical point of view. A second issue was to clarify the origin of potential autonomic responses during both tests; are they related to baroreflex activity or rather a consequence of the pain experience per se? The study was performed in 30 volunteers aged 19-57 (median 24) years, and consisted of a single session including one CPT (4 ± 0.2°C) and one HIT (47 ± 0.5°C) with a cut-off-point of 5 minutes. Participants were randomly assigned to sequence order (the sequence of both trials was alternated) and groups were paralleled with respect to gender. Cardiovascular, respiratory and electrodermal activities as well as subjective pain intensity were continuously monitored. Pain detection and tolerance thresholds as well as pain unpleasantness and nervous tension were assessed additionally. Both tests were found to be comparable with respect to intensity of subjective pain and time course, but a significantly higher blood pressure increase during CPT could be observed, compared to the HIT. In conclusion, the HIT appears to be less confounded with baroreflex activity and hence seems to be a more adequate tonic pain model. The second study tested the internal validity of inter-digital web pinching (IWP) with regard to its potential as DNIC-trigger. 24 gender-matched participants, aged 21-54 (median 25) years, volunteered for the controlled study. The protocol included the assessment of thermal and mechanical perceptual wind-up (WU) before and after a HIT (47.5 °C) or an IWP (15 N) of 2 minutes duration each. WU pain was induced by 10 repetitive (1 Hz) contact heat (max. 49°C; 5 5 mm thermode) or 10 ballistic impact stimuli (0.5 g at 9m/s) on the phalanges of the non-dominant hand. Cardiovascular and corrugator muscle activity as well as pain experience were permanently monitored. Both heterotopic noxious counter-stimulation (HNCS) types produced a similar pain experience, but a more pronounced cardiovascular activity was observed for the HIT. Painful water immersion is though accompanied by a stronger baroreceptor activity. WU pain was significantly reduced for both pain modalities, although the inhibition was somewhat stronger for the HIT than the IWP. The IWP, being practically uncontaminated by baroreflex sensitivity (BRS), proved its validity as DNIC-trigger. The third study investigated temporal characteristics of electrically elicited pain and nocifensive RIII-reflex activity in a gender-balanced sample of 28 volunteers aged 21-38 (median 27) years, using IWP as HNCS, a tonic pain model previously validated to be BRS-unrelated. Sex-related differences in the post HNCS time courses of pain perception were identified with women demonstrating a more rapid return to baseline compared to men. Interestingly, an opposite pattern was observed regarding nociceptive reflex activity with a steeper return rate of electromyographic responses in males, whereas those of women remained attenuated over the entire observation period. These findings may reflect a stronger defensive response to pain in women.