Am. Aloisi et I. Ceccarelli, Role of gonadal hormones in formalin-induced pain responses of male rats: Modulation by estradiol and naloxone administration, NEUROSCIENC, 95(2), 2000, pp. 559-566
The aim of this study was to assess the possible mediation of endogenous op
ioids in the effects of gonadal hormones on the responses to formalin pain.
We studied the effects of intracerebroventricular injection of estradiol a
nd/or naloxone on the magnitude and time-course of the formalin-evoked beha
vioural and hormonal responses of intact and gonadectomized male rats. Anim
als were gonadectomized or left intact; on days 20 and 21 after surgery, th
ey were intracerebroventricularly injected with 17 beta-estradiol (1 mu g/5
mu l) or saline. On day 22, the animals received naloxone (2.5 mu g/5 mu l
) or saline intracerebroventricularly and then, 15 min later, were subcutan
eously injected with formalin (50 mu l, 5%) or only pricked with a syringe
needle in the dorsal hindpaw. The rats were then introduced to a testing ap
paratus where the formalin-induced licking, flexing and jerking of the inje
cted limb and the other spontaneous behaviours were recorded for 60 min. At
the end of the test, the animals were killed and blood was collected from
the trunk. Gonadectomy and naloxone increased flexing duration independentl
y of the other treatments. In gonadectomized rats, estrogen increased licki
ng duration and decreased paw-jerk frequency during the first phase (0-15 m
in) of the formalin test. During the second phase (16-60 min), licking was
increased by estrogen only in intact animals. Treatment with naloxone compl
etely abolished all these modifications. The three measures of activity (re
aring, inner and outer crossing) showed that while in sham-treated animals
the gonadectomy-induced decrease in activity was completely counteracted by
estrogen administration, in formalin-treated animals the gonadectomy-induc
ed decrease was not affected by estrogen. In fact, estrogen appeared to fur
ther depress the motor activities in the formalin groups. Naloxone reversed
these modifications only for outer crossing frequency, blocking the gonade
ctomy-induced decrease in sham-treated animals. Corticosterone plasma level
s were increased by formalin only in estrogen-treated animals, independentl
y of naloxone.
In conclusion, these data indicate an important role of both male gonadal h
ormones and estrogen in formalin-pain responses, acting through opiate and
non-opiate mechanisms. (C) 1999 IBRO. Published by Elsevier Science Ltd.