Men are typically reported to have higher pain thresholds than women.
Gonadal hormones, particularly
testosterone for males, may contribute to this effect. This study tested whether changes in the male hormonal milieu early or late in development alter the inflammatory
pain induced by
carrageenan (CARR, 3%, intraarticular). Male rats were either gonadectomized or
sham gonadectomized neonatally. Once adults, the same rats underwent either
sham surgery or
gonadectomy, and received a
testosterone or oil implant. After baseline testing two weeks later, animals were tested in response to mechanical and thermal stimulation following CARR-induced
inflammation and injection of saline, 1 mg/kg, or 5 mg/kg
morphine.
Hormone alterations did not affect baseline responses, but CARR induced mechanical and
thermal hyperalgesia in the injured limb.
Gonadectomy in adult males injected with saline enhanced
inflammation-induced sensitivity to mechanical but not thermal stimulation and the effect was reversed by
testosterone. After
inflammation, saline-treated males gonadectomized neonatally displayed lower mechanical threshold than control
sham animals but this effect was not reversed by
testosterone. Both doses of
morphine increased mechanical and thermal thresholds. However, compared with the control group, 1 mg/kg
morphine was equally effective in reducing
mechanical hyperalgesia among groups of animals gonadectomized as adults, but less effective in males gonadectomized neonatally. The results suggest that in males: 1. the antihyperalgesic effect of
testosterone (or its metabolites) in CARR-induced
inflammation is established during development and maintained by circulating levels of
testosterone in adulthood; 2. the nociception-related interaction between the
opioid and gonadal systems influences the sensitivity to mechanical stimuli and is likely established during the period of sexual differentiation.