Estrogen Modulates the Visceromotor Reflex and Responses of Spinal Dorsal Horn Neurons to Colorectal Stimulation in the Rat

Abstract

Many gastrointestinal pain syndromes are more prevalent in women than men, suggesting a gonadal steroid influence. We characterized the effects of estrogen on two responses to colorectal distention (CRD) in the rat: the visceromotor reflex (vmr) and L6-S1 dorsal horn neuron activity (ABRUPT and SUSTAINED neurons). Ovariectomized rats were injected with estrogen, and responses to innocuous and noxious intensities of CRD were measured between 4 hr and 14 d after injection and compared with ovariectomized and intact, cycling rats. Plasma estrogen levels were determined at each time point. Ovariectomy significantly decreased the magnitude of the vmr and ABRUPT neuron response to CRD compared with cycling rats. Four and 48 hr after estrogen injection (10 microg), the magnitude of the vmr and ABRUPT neuron response returned to the level or greater than that of cycling rats. All responses were comparable with ovariectomized rats by 7 d. These results paralleled the plasma estrogen concentration. Fifty micrograms of estrogen did not further increase the magnitude of the vmr or neuronal response 48 hr after estrogen but did extend the period of the increased ABRUPT neuron response to 14 d. Estrogen did not affect the response of SUSTAINED neurons. In a separate experiment, the response to innocuous CRD was sensitized in estrogen-treated rats but not ovariectomized or cycling rats. The present data suggest that estrogen modulates the spinal cord processing and reflex responses to innocuous and noxious colorectal stimuli in female rats and may contribute to alterations in sensory processing associated with irritable bowel syndrome.

Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats

“…Colorectal distention (CRD) induces abdominal contractions, and this visceromotor response (VMR) is used to assess visceral pain. Estradiol induces hyperalgesia in response to CRD in rats (29). To test whether BPA affects colorectal sensitivity, we measured the VMR to graded intensities of CRD.…”

“…However, visceral nociception has never been considered as a target for xenoestrogen chemicals such as BPA, although estrogens enhance visceral sensitivity to colorectal stimuli (29). The gastrointestinal tract is highly innervated, and primary sensory afferents convey information between intestine and central nervous system, adapting nociceptive behavior.…”

“…Altogether, a sex difference in intestinal permeability and inflammation (22), the prevalence of irritable bowel syndrome in women (23), the fluctuations of irritable bowel syndrome-associated abdominal pain in women during their menstrual cycle (24), as well as the wide expression of estrogen receptors (ERs) in human fetal and adult colonic mucosa (25,26) suggest that estrogens play a key role. In animal studies, estrogen action on intestinal permeability, inflammation, and viscerosensitivity are controlled by ERs in gut epithelial cells and sensory neurons, the latter conveying peripheral information to the central nervous system (27)(28)(29). Therefore, we assumed that BPA may target these receptors.…”

Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male

“…OVX rats that were to receive exogenous estrogen received a single dose of estradiol benzoate (1 ng, 10 ng, 1 g, 10 g, or 100 g/100 l sesame oil, s.c.) 48 h before testing. This regimen (single subcutaneous injection) has been used previously in neuroendocrinology (Berglund et al, 1988;Priest et al, 1995) and in the pain field (Ji et al, 2003(Ji et al, , 2005. The rationale for using a 100 g dose of estradiol for most of our experiments was that this dose is known to most reliably induce lordosis behavior in rats (for review, see Clark, 1993a).…”

Estrogenic influences in pain processing

“…the response to a noxious stimulus applied to the rodent's tail, which is considered to be a spinal reflex (Irwin et al, 1951), is influenced by estrogens (Frye et al, 1992;Gordon and Soliman, 1996). Albeit this effect could be due to a facilitating effect at the supraspinal level, in vivo electrophysiological experiments demonstrate that the modulation of the response takes place in the spinal cord, something that also has been shown for the estrogenic regulation of visceral sensitivity (Ji et al, 2003;Ji et al, 2011;Tang et al, 2008). Pregnancy-induced analgesia in the rat also has an unambiguous spinal component since intrathecal but not intracerebroventricular administration of naloxone (Sander et al, 1989) attenuates it.…”