Pain Perception, Brain Connectivity, and Neurochemistry in Healthy, Capsaicin-Sensitive Subjects

Most of the occupational exposure limits (OELs) are based on local irritants. However, exposure to much lower concentrations of irritant substances can also lead to health complaints from workers. Exposure to irritants is often accompanied by strong unpleasant odors, and strong odors might have distracting effects and hence pose a safety risk. The findings obtained in human exposure studies with chemically sensitive, stressed, or anxious persons suggest that their ability to direct attention away from the odorous exposure and to focus on a cognitive task is reduced. In addition, after repeated odor exposure, these persons show signs of sensitization, i.e., difficulties in ignoring or getting used to the exposure. The question arises as to whether certain health conditions are accompanied by a change in sensitivity to odors and irritants, so that these persons are potentially more distracted by odors and irritants and therefore more challenged in working memory tasks than nonsusceptible persons. In our study, susceptible persons with sensory airway hyperreactivity ("capsaicin-sensitive") respond more strongly to mechanical skin stimuli than controls and show altered network connectivity. Capsaicin-sensitive subjects have a lower pain threshold and thus are more sensitive to mechanical skin stimuli. The intrinsic functional connectivity of their saliency network is higher, and the lower the GABAergic tone of the thalamus, the higher their pain sensitivity to mechanical stimuli. It seems that the increased communication between resting-state networks promotes a stronger perception of the sensory input signal. The results can be used to inform about actual risks (i.e., attention diversion and increased risk of accidents) and "pseudo" risks such as odor perception without a negative impact on one's well-being. This way, uncertainties that still prevail in the health assessment of odorous and sensory irritating chemicals could be reduced.