Exploring the Influence of Testosterone on Pain Perception and Modulation Among Men with Low and Normal Testosterone Concentrations

Background: Pain perception varies considerably between individuals, with sex differences likely contributing to this variability. These differences appear to involve multiple factors, including sex hormones, although the underlying mechanisms of modulation remain unclear. Purpose: To explore how variations in free testosterone influence pain perception and modulation mechanisms in men. Patients and Methods: A non-probabilistic convenience sampling was used to recruit a total of 12 men with low testosterone and 16 controls for this cross-sectional experimental study. Pain sensitivity was evaluated via heat pain threshold (HPT) and heat pain tolerance (HPTol) using a contact thermode placed on the left forearm. Pain modulation was assessed through conditioned pain modulation (CPM) responses using a counter-irritation protocol with heat pain stimulation as test stimuli applied before and after a cold pressor test serving as the conditioning stimulus. Temporal summation of pain (TSP) was assessed using 2 minutes constant heat pain stimulation. Results: Pain perception (HPT and HPTol) was significantly lower in low testosterone compared to controls (p = 0.02). Free testosterone levels were positively correlated with HPTol (r = 0.40, p = 0.03). Pain modulation responses were similar in low-testosterone and those in the control group. No significant between-groups differences were observed for CPM and TSP responses (all p > 0.90). Conclusion: Control men showed lower pain sensitivity than low-testosterone participants, supporting an antinociceptive effect of testosterone that may partly contribute to sex differences in pain. Keywords: pain perception, pain threshold, pain modulation, conditioned pain modulation, temporal summation, sex hormones, testosterone, men