Aromatase (estrogen synthase) activity in the dorsal horn of the spinal cord: functional implications

The presence of aromatase (estrogen synthase) in neurons in the dorsal horn of the spinal cord in Japanese quail suggests that estrogens produced locally from androgens could control spinal sensory processes including nociception. We used the hot water nociceptive test (54 degrees C) to appraise the long-term effect of an inhibition of aromatization on the foot withdrawal latency in male quail. Four weeks after the ablation of their main source of testosterone (testes), castrated males displayed a significantly higher foot withdrawal latency than gonadally intact males. A prolonged treatment with subcutaneous capsules filled with testosterone or 17 beta-estradiol restored the baseline latency within 2 weeks. The effect of testosterone in castrated quail was almost completely blocked by systemic injections of Vorozole(TM), a nonsteroidal aromatase inhibitor or tamoxifen, an estrogen receptor antagonist (one injection per day for 10 days). Taken together, these data demonstrate for the first time to our knowledge an effect of estrogens formed by aromatization of androgens on nociception. Because aromatase-immunoreactive neurons and aromatase activity are present in the dorsal horns of the spinal cord, this control of pain thresholds is presumably mediated, at least in part, by estrogens produced at the spinal level that act locally via slow, presumably genomic, mechanisms mediated by the activation of spinal nuclear estrogen receptors.