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.

Fig. 1.

A, The plasma estrogen concentration from ovariectomized rats (OVx) and 7–10 hr, 48 hr, and 7 d after a single injection of 10 or 50 μg of estrogen to ovariectomized rats. Data are pooled from animals used in the vmr and single-unit studies. *p < 0.05 compared with OVx or same dose of estrogen at 7 d. Data were analyzed with Kruskal–Wallis one-way ANOVA on ranks, followed by Dunn's multiple comparison test. B, The volume–pressure relationship of the distention balloon in ovariectomized and estrogen-treated rats. The volume was increased in 0.5 ml increments, and the corresponding pressure was recorded.

Fig. 2.

The magnitude of the vmr (mean area under the curve) after graded intensities of CRD. A, The magnitude of the vmr for intact female and ovariectomized rats. B, The effects of time after estrogen replacement on the magnitude of the vmr. C, The effects of dose of estrogen on the magnitude of the vmr. *p < 0.05 compared with intact females in A and OVx in B and C.

Fig. 3.

The magnitude of the vmr for the first 12 distentions at 20 mmHg. Every third data point is shown. Trend lines were determined from the 12 data points. * indicates significant increase in slope versus OVx. p < 0.05.

Fig. 4.

The mean magnitude of response of dorsal horn neurons to graded intensities of CRD. A, ABRUPT neurons.B, SUSTAINED neurons. Insets, Examples of a peristimulus time histogram (top trace) and spike discharge (middle trace) of an ABRUPT and a SUSTAINED neuron to 80 mmHg CRD (bottom trace). * indicates significantly greater response compared with ovariectomized rats. p < 0.05.

Fig. 5.

The mean magnitude of the response of ABRUPT (A, B) or SUSTAINED (C) dorsal horn neurons to graded intensities of CRD after 10 μg (A, C) or 50 μg (B) of estrogen. # indicates significantly greater response compared with ovariectomized and 7 d post-estrogen rats. * indicates significantly greater response compared with ovariectomized rats. *#p < 0.05.