Administration of testosterone might increase the feeling of pain, study finds

An experimental study has found that individuals showed increased vigilance and sustained attention levels when they were administered testosterone. They rated the same stimulus as more painful compared to the ratings they gave when they received placebo. Тheir brain activity also exhibited an electrical pattern associated with paying greater attention to the stimulus at hand. The study was published Psychoneuroendocrinology.

Testosterone is a hormone primarily produced in the testes of males and ovaries of females. It is also produced in smaller amounts by the adrenal glands. Testosterone plays a key role in the development and maintenance of male sexual characteristics, including facial and body hair, muscle mass, and bone density. It regulates sexual desire, the production of sperm, and displays a wide set of effects on a number of other systems in the body.

It has also been suggested that it modulates the perception of pain. Previous studies have reported higher levels of testosterone generated by the body to be associated with lower sensitivity to pain and higher activation of brain regions involved in pain inhibition.

Other studies reported daily fluctuations of testosterone levels in the body to be inversely associated with reported pain severity among female patients with fibromyalgia, a chronic disorder characterized by widespread pain and tenderness in muscles, joints and soft tissues. This again confirmed the role of testosterone in reducing pain.

Study author Shiwei Zhuo and his colleagues wanted to verify this pain reducing role of testosterone and also study brain activity associated with this changed perception of pain. They organized a double-blind experimental study.

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Participants were 30 male students from Shenzhen University in China. The researchers report that all participants were males because previous studies that included testosterone gel administration only had male participants. Female reactions to the administration of testosterone are not known.

There eight experimental sessions and each participant underwent all of them. These conditions included combinations of whether testosterone gel was administered to the participant or a placebo, whether the electric shock participant received was painful or non-painful, and whether it was predictable or uncertain.

In sessions where participants received testosterone, a 1.5% testosterone gel (Androgel) was applied to their shoulders and upper arms. In the placebo sessions, participants had an identical-looking gel with no testosterone applied in the same way. Gels were applied by a male research assistant who did not know whether he was applying the testosterone gel or placebo. In all experimental sessions, participants had electrodes attached to their left hand that either delivered a painful or a non-painful electric stimulation.

Depending on the session, the researchers presented a square or a triangle to participants that in one group of sessions indicated with certainty whether the electrostimulation that was to follow would be painful. In the other group of sessions (uncertain trials), it was not possible to accurately predict what the electric stimulation will be like based on these pictures. Participants underwent electroencephalographic (EEG) recording during the experimental sessions.

Results showed that participants reported higher intensities of pain when they were administered testosterone compared to ratings they gave in placebo sessions. Pain was also rated as higher in sessions when painful electrostimulations were unpredictable.

Analysis of EEG recordings showed greater N1 amplitude in situations when participants received painful electrical stimulations and when they received testosterone. The study authors tested a statistical model in which they assumed that the N1 neural activity mediated the effect of testosterone on the perceived intensity of pain. Data confirmed that such a model is possible.

The N1 neural activity is an event related potential associated with paying greater attention to the stimulus at hand. It is a negative deflection in the electroencephalogram waveform that typically peaks around 100 milliseconds after the onset of a sensory stimulus, such as a sound or a visual cue.

“When perceiving painful or non-painful somatosensory stimulation, testosterone enhanced the amplitude of the N1 component that reflects the early stage of somatosensory processing, thus further leading to an increase of subjective pain intensity ratings,” the researchers wrote.

“When anticipating the upcoming somatosensory stimulation, testosterone increased the expected pain intensity ratings upon viewing the predictability cues, accompanied with decreased low-frequency α-oscillation power recorded after the predictability cues but before somatosensory stimulation.”

“These results provide some causal evidence for the role of testosterone in enhancing the expectation and perception of somatosensory event, irrespective of whether the somatosensory event was painful or nonpainful.”

The paper provides a valuable contribution to the study of behavioral and neural effects of testosterone administration. However, it should be noted that these results are valid only for males. Additionally, all participants were relatively young university students. Effects on other age groups might not be the same.

The study, “Testosterone administration enhances the expectation and perception of painful and non-painful somatosensory stimuli”, was authored by Shiwei Zhuo, Yinhua Zhang, Chennan Lin, and Weiwei Peng.