Sex differences have been observed repeatedly in
chronic pain syndromes in both humans and animals, with females showing a higher incidence; it is likely that the
gonadal hormones are responsible for these differences. To examine the role of male
gonadal hormones on repetitive nociceptive stimulation, we studied male rats, half of them gonadectomized (GDX) and half left intact (INT). Starting from the third week after
gonadectomy, they were subjected to the
formalin test once a week for 3 weeks (50 micro l
formalin 5% injected s.c. in the dorsum of the hind paw: right, left, and right).
Formalin-induced licking, flexing, and jerking of the injected paw were recorded and analyzed for each of the three trials. Analysis of variance showed significant differences between GDX and INT animals depending on the trial considered: Trial 1: the GDX and INT groups showed a similar amount of licking, flexing, and paw-jerk; Trials 2 and 3: these responses showed a sort of adaptation in INT animals, not present in the GDX ones, resulting in lower levels of
pain responses in INT than GDX.
Corticosterone was higher in GDX animals than in INT animals.
Testosterone plasma levels were drastically decreased by
gonadectomy, whereas
estradiol was increased. These data indicate that male
gonadal hormones play a key role in inhibiting the behavioral responses to repeated nociceptive stimulation. This suggests that the lower incidence of
chronic pain syndromes in males could be caused by the presence of these
hormones.