Estradiol attenuates spinal cord injury-related central pain by decreasing glutamate levels in thalamic VPL nucleus in male rats
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Central neuropathic pain (CNP) is a complicated medical problem that involves both the spinal and supraspinal regions of the central nervous system. Estrogen, a neuroprotective agent, has been considered a possible candidate for CNP treatment. In this study, we examined the effects of a single dose of 17β-estradiol on glutamate levels in the ventral posterolateral (VPL) nucleus of the rat thalamus. Furthermore, we determined whether there was a correlation between glutamate levels and neuropathic pain induced by unilateral electrolytic spinothalamic tract (STT) lesion. STT lesioning was performed in male Wistar rats at the T8-T9 vertebrae; rats were then administered 17β-estradiol (4 mg/kg, i.p.) 30 min after injury. Glutamate samples were collected using a microdialysis probe and quantified by high performance liquid chromatography. Mechanical allodynia (MA) and thermal hyperalgesia (TH) thresholds were measured pre-injury and 7, 14, and 28 days post-injury. We found that STT lesion significantly increased glutamate levels in the ipsilateral VPL nucleus 14 and 28 days post-injury; this was accompanied by allodynia and hyperalgesia in the hind paws of the rats. Administering 17β-estradiol to the rats decreased glutamate levels in the ipsilateral VPL nucleus and significantly increased MA and TH thresholds. These results suggest that glutamate in the VPL nucleus of the thalamus is involved in the pathology of neuropathic pain after STT injury; furthermore, 17β-estradiol may attenuate this neuropathic pain by decreasing glutamate levels.
KeywordsCentral neuropathic pain Estradiol Glutamate Spinal cord injury VPL nucleus
We are grateful to Dr. Hedayat Sahraei and Dr. Asghar Ghasemi for the critical reading of the manuscript and Hamid Reza Falahatpishe for excellent technical assistance. This project was a part of Ph.D. dissertation supported by the Neuroscience Research Center of Baqiyatallah University of Medical Sciences & Neurobiology Research Center of Shahid Beheshti University of Medical Sciences.
Conflict of interest
The authors declare that there are no conflicts of interest, financial or otherwise in the publication of this manuscript.
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