The role of anxiety in the perception of pain: exploring the cumulative & temporal mechanisms of hypercapnic analgesia

Background Anxiety, evoked by continuous inspiration of a 5 – 8% CO2 mixture, has been found to have an analgesic eLect on self-reported pain. The precise mechanism whereby this effect obtains remains unknown. Methods The present study tested whether temporal summation, the psychological counterpart of wind-up, is involved in hypercapnic analgesia. 21 healthy participants received painful transcutaneous electrical stimuli of varied intensity, during continuous inhalation of 7.5% CO2 mixture and medical air, presented in a single-blinded counterbalanced order. Continuous pain ratings were acquired to measure the temporal development of the pain response. Several points and events of interest that characterise the pain response profile were extracted from the continuous data. Results Mixed-eLects modelling demonstrated a reduction of all pain measures during inspiration of the anxiogenic mixture, but not air. This was accompanied by an increase in the psychological and physiological measures of anxiety. Analyses of the characteristic measures of temporal summation suggested that the hypercapnic mixture has an analgesic property evident from the start of the pain response. The same was true for the remainder of the response, the adaptation period, where pain ratings were also inhibited. The reduced pain ratings persisted during the remainder of the response. Anxiety was found to be a mediating factor for summative pain ratings but not the temporally sensitive TS measures, suggesting an overall, cumulative effect. Conclusions The findings provide an explanation for the previously observed low self-reported pain during the inhalation of an anxiogenic hypercapnic mixture. ### Competing Interest Statement The authors have declared no competing interest.