Background & Aims
Research on sex differences in pain largely show that women experience greater pain than men [1]. Sex differences in pain extend to perceived pain relief following placebo treatments, where women with chronic orofacial pain show greater placebo hypoalgesia compared to men following experimental manipulation [5]. Sexual dimorphism in pain and placebo is significant yet often overlooked in clinical settings because the mechanisms underlying this disparity remain unclear [6]. A possible explanation lies in the different concentrations of sex hormones both between and within sexes. In particular, the protective effects of testosterone on pain have been shown in previous research [2, 3, 4], yet the extent to which these effects translate to placebo responsiveness is still in question. This study aimed to investigate the effects of sex hormones on pain experience and placebo effects in a large cohort of chronic pain and pain-free participants.
Methods
Specimens from participants diagnosed with Temporomandibular disorders (n = 311) and pain-free participants (n = 328) were collected to determine gonadal hormone levels. Then, participants completed a quantitative sensory pain test to assess pain sensitivity. Participants reported their pain intensity using a visual analogue scale (VAS). This allowed a high, low, and moderate level of pain tailored to each participant’s pain sensitivity to be used for the experiment. After, participants completed a classical conditioning with suggestions paradigm to study placebo effects. We tested placebo responsiveness in a laboratory setting by using two distinct levels of individually tailored painful stimulations (high and low pain) to reinforce expectations and provide a hypoalgesia experience (conditioning phase). Afterward, both pain levels were surreptitiously set at a moderate pain to test for placebo effects (testing phase). Pain was assessed as the primary outcome using the VAS.
Results
Among TMD patients, women showed higher chronic pain severity, but equal interference compared to men. Testosterone levels were negatively correlated with chronic pain severity (r = -0.204; p < 0.001) and positively correlated with pain tolerance (r = 0.152; p < 0.001). For all participants, women showed lower pain thresholds (F(1, 797) = 4.508; p = 0.034) and tolerance (F(1, 797) = 14.333; p < 0.001) than men. Further, women showed greater levels of baseline expectations and perceived effectiveness of treatment compared to men (baseline expectations: women mean = 48.31, SEM = 1.03; men mean = 43.78, SEM = 1.49; p = 0.006) (perceived effectiveness: women mean = 65.64, SEM = 1.04; men mean = 61.77, SEM = 1.50; p = 0.017). Higher testosterone levels were associated with lower levels of baseline expectations (r = -0.095, p = 0.017) and perceived effectiveness (r = -0.12, p = 0.003). Women showed greater placebo effects than men. However, hormone levels did not influence placebo effects.
Conclusions
The inclusion of sex as a biological variable in pain and placebo research is critical for the development of medical interventions and treatments tailored to patients’ needs. This study demonstrated that varied concentrations of sex hormones contribute to differences in pain experience, including pain sensitivity and tolerance and expectations regarding pain relief. However, gonadal hormone levels were not associated with the sex differences found in placebo effects, highlighting the importance of future research to elucidate the mechanisms underlying sexual dimorphism in placebo hypoalgesia. The findings of this study may be used to advance current knowledge in sex differences as they relate to pain and placebo science.
References
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Presenting Author
Jewel N. Clark
Poster Authors
Topics
- Assessment and Diagnosis