The Effect of Caffeine Withdrawal on Pain Processing in Healthy Adults

Louise A Kingsford

Caffeine is known to have potent analgesic effects, yet the effects of caffeine withdrawal on pain remain unclear. Pain chronification is influenced by altered processing within the pain modulation pathways involving the Locus Coeruleus (LC), which is also affected by caffeine. Caffeine withdrawal is proposed to reduce LC firing, changing how painful sensations are processed. This study aimed to explore the influence of altered LC firing and its effect on pain perception by leveraging the neurophysiological changes seen in caffeine withdrawal. The present study (N = 16) utilised pupillometry and conditioned pain modulation assessments in healthy adults to examine changes in pupil diameter (LC activity) and pressure pain threshold ratings in a caffeine-withdrawn and caffeine (control) condition. Results showed no influence of caffeine withdrawal on pain sensitivity in the hands compared to the control condition (partial η2 = 0.09, p = 0.24). Caffeine withdrawal also did not affect pupil diameter compared to the control condition either before (partial η2 = 0.08, p = 0.34) or after the light stimulus (partial η2 = 0.04, p = 0.59). Although these results were not significant, the moderate effect sizes suggest that the sample size was insufficient to adequately test these hypotheses. These findings do not align with previous research. As this is an unexplored functional relationship, further studies are recommended. Low sample size was a key limitation in this study; therefore, results must be interpreted cautiously.

The Effect of Caffeine Withdrawal on Pain Processing in Healthy Adults

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