Sex and hormonal variations in the development of at-level allodynia in a rat chronic spinal cord injury model

Abstract

The development of central neuropathic pain varies among patients with spinal cord injury (SCI). The factors contributing to the development and perpetuation of segmental pain (at-level allodynia) has been the focus of ongoing experiments in our laboratory. One such factor is hormonal status. We have shown previously, using a male rat model of SCI, that a severe contusion injury is necessary for the development of allodynia in trunk regions at and just above the level of a T8 injury. In this study, we examined at-level sensitivity for SCI ovariectomized (ovx) and cycling female rats as well as for SCI males implanted with either a placebo pellet or one that slowly releases 17beta-estradiol. The proportion of ovx SCI female rats and placebo-treated SCI males displaying pain-like behaviors to touch/pressure of at-level dermatomes up to 6 weeks post-injury (67% and 75%, respectively) was similar to our previous studies on SCI males (69%). In contrast, significantly fewer cycling SCI female rats and 17beta-estradiol treated SCI male rats showed sensitivity to touch at-level (26% and 30%, respectively). These results implicate 17beta-estradiol as a potential target that can readily be modulated to prevent segmental pain following SCI.

Figure 1

Lesion Epicenters - Typical lesion epicenters from three rats with pain-like responses to touch/pressure at-level. The cross-section to the left is from an ovariectomized female (mean five-week allodynia score of 5.0; 224 Kdyn impactor force), the middle section is from a placebo-treated male (mean allodynia score of 7.0; 221 Kdyn), and the section to the right is from an estradiol-treated male (mean allodynia score of 6.8; 216 Kdyn). The sections were stained with both luxol fast blue (indicates the presence of myelin) and cresyl violet (to stain Nissl substance in nervous tissue).