分类： 生物学 >> 神经生物学 提交时间： 2017-07-24
摘要： Although depression-induced altered pain perception has been described in several laboratory and clinical studies, its neurobiological mechanism in the central nervous system, particularly in the spinal dorsal horn remains unclear. In this study, we therefore aimed to clarify whether nociceptive sensitivity of neuropathic pain is altered in the olfactory bulbectomy (OB) model of depression and whether glucocorticoid receptor (GR), which is involved in the etio-pathologic mechanisms of both major depression and neuropathic pain, contributes to these processes in the spinal dorsal horn of male Sprague-Dawley rats. The results showed that mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation (SNL) were attenuated in OB-SNL rats with decreased spinal GR expression and nuclear translocation, while NOB (non-olfactory bulbectomy)-SNL rats showed an increased spinal GR nuclear translocation. Decreased GR nuclear translocation with normal mechanical nociception and hypoalgesia of thermal nociception were observed in OB-Sham rats, too. Intrathecal injection of GR agonist dexamethasone (4 µg / rat / day for 1 week) eliminated the attenuating effect of depression on the nociceptive hypersensitivity in OB-SNL rats and aggravated neuropathic pain in NOB-SNL rats, associating with the up-regulation of BDNF, TrkB and NR2B expression in the spinal dorsal horn. The present study shows that depression attenuates the mechanical allodynia and thermal hyperalgesia of neuropathic pain and suggests that altered spinal GR-BDNF-TrkB signaling may be one of the reasons for depression-induced hypoalgesia.
分类： 生物学 >> 神经生物学 提交时间： 2017-03-31
摘要： Although depression-induced altered pain perception has been described in several laboratory and clinical studies, its neurobiological mechanism in the central nervous system, particularly in the spinal dorsal horn remains unclear. In this study, we therefore aimed to clarify whether nociceptive sensitivity of neuropathic pain is altered in the olfactory bulbectomy (OB) model of depression and whether glucocorticoid receptor (GR), which is involved in the etio-pathologic mechanisms of both major depression and neuropathic pain, contributes to these processes in the spinal dorsal horn of male Sprague-Dawley rats. The results showed that mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation (SNL) were attenuated in OB-SNL rats with decreased spinal GR expression and nuclear translocation, while NOB (non-olfactory bulbectomy)-SNL rats showed an increased spinal GR nuclear translocation. Decreased GR nuclear translocation with normal mechanical nociception and hypoalgesia of thermal nociception were observed in OB-Sham rats, too. Intrathecal injection of GR agonist dexamethasone (4 µg / rat / day for 1 week) eliminated the attenuating effect of depression on the nociceptive hypersensitivity in OB-SNL rats and aggravated neuropathic pain in NOB-SNL rats, associating with the up-regulation of BDNF, TrkB and NR2B expression in the spinal dorsal horn. The present study shows that depression attenuates the mechanical allodynia and thermal hyperalgesia of neuropathic pain and suggests that altered spinal GR-BDNF-TrkB signaling may be one of the reasons for depression-induced hypoalgesia.
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