c-Fos expression in the spinal cord of female rats with artificial ureteric calculosis

Rats with an artificial stone in the left ureter display spontaneous pain behavior (ureteral 'crises') and referred hyperalgesia/contraction in the ipsilateral oblique musculature. To evaluate neuronal activation in both sensitive and motor pathways in this model, c-Fos expression was studied in the spinal cord of calculosis rats vs. sham controls. Fos-labeled cells were never observed in sham controls. In stone rats, they were found in the T10-L2 segments, throughout the dorsal horn, significantly more on the left than the right side (P < 0.002). Fos-labeled cells were also found in lamina IX, containing motoneurons; at the T11-T12 level, these were significantly more on the left than the right side (P < 0.03). Nociceptive input from the ureter thus activates not only sensory but also efferent neurons in the spinal cord, suggesting the triggering of reflex arcs by the visceral focus

Estradiol and testosterone differently affect visceral pain-related behavioural responses in male and female rats

In the study of pain, the presence of sex differences is well known, with female subjects being more affected in a number of chronic painful conditions; however, the underlying mechanisms and the involvement of gonadal hormones, are still controversial. This study evaluated visceral pain in a validated rat model of artificial calculosis and the effects of estradiol and testosterone administration. Adult male and female rats were divided into groups and treated with one of the substances or Oil (vehicle) for 5 days, starting 2 days before surgery, with half receiving an artificial calculosis (Stone) and half only a sham (Sham) procedure. The animals' behaviour (ureteral crises, frequency and duration) were recorded for 72 h; estradiol and testosterone plasma levels were determined in all groups at the end of the observation period. After surgery, only Stone rats showed ureteral pain crises, with a significant sex difference in the Oil-treated groups in which the number and duration of crises were higher in females than in males. This difference was not present in the estradiol-treated groups in which ureteral crises were decreased only in females while testosterone treatment had no effect in either sex. Estradiol and testosterone plasma levels were affected by treatments in both sexes. These results confirm that, also in this model of visceral pain, females experience more pain than males; moreover, they show that supraphysiological levels of estradiol, but not of testosterone, are analgesic only in females. A dose and sex-dependent efficacy of gonadal hormones is suggested and discussed