Department of Pharmacology, Biological Sciences Building, Federal University of Parana, Curitiba, PR, Brazil.
Cephalalgia. 2020 Jun;40(7):689-700. doi: 10.1177/0333102419896539. Epub 2019 Dec 19.
To evaluate whether intraganglionic calcitonin gene-related peptide induced differential migraine-like responses in male and female rats.
Calcitonin gene-related peptide was injected in the trigeminal ganglion of male and female rats followed by assessment of periorbital mechanical allodynia with von Frey hairs. The influence of systemic treatment with sumatriptan or intraganglionic treatment with minocycline and propentofylline was determined on the calcitonin gene-related peptide-induced mechanical allodynia in male and female rats. One additional group was exposed to an aversive light 24 h after calcitonin gene-related peptide priming, followed by evaluation of periorbital mechanical threshold, and another group was tested in the elevated-plus maze.
Intraganglionar calcitonin gene-related peptide-induced periorbital mechanical allodynia in female (0.5 to 6 h) and male rats (0.5 to 4 h). Systemic sumatriptan briefly attenuated the mechanical allodynia, but intraganglionar minocycline or propentofylline injection was effective only in male rats. Calcitonin gene-related peptide induced photic sensitivity in female and male rats (lasting 4 h and 1 h, respectively), as well as anxiety-like behavior.
Intraganglionar calcitonin gene-related peptide may play a major role in migraine-like responses, including periorbital mechanical allodynia, light sensitivity and anxiety like-behavior. Female rats are likely to be more susceptible to calcitonin gene-related peptide effects and a better understanding of the sexual dimorphism in calcitonin gene-related peptide signaling may help to improve migraine therapy.
评估神经节内降钙素基因相关肽是否会引起雄性和雌性大鼠产生不同的偏头痛样反应。
在雄性和雌性大鼠的三叉神经节内注射降钙素基因相关肽,然后用 von Frey 毛发评估眶周机械性痛觉过敏。确定全身性给予舒马曲坦或三叉神经节内给予米诺环素和丙戊茶碱对雄性和雌性大鼠降钙素基因相关肽诱导的机械性痛觉过敏的影响。还有一组大鼠在降钙素基因相关肽引发作用 24 小时后暴露于厌恶光下,然后评估眶周机械阈值,另一组大鼠在高架十字迷宫中进行测试。
神经节内降钙素基因相关肽诱导雌性(0.5 至 6 小时)和雄性大鼠(0.5 至 4 小时)眶周机械性痛觉过敏。全身性舒马曲坦短暂减弱了机械性痛觉过敏,但三叉神经节内米诺环素或丙戊茶碱注射仅对雄性大鼠有效。降钙素基因相关肽诱导雌性和雄性大鼠产生光敏感性(分别持续 4 小时和 1 小时)以及焦虑样行为。
神经节内降钙素基因相关肽可能在偏头痛样反应中起主要作用,包括眶周机械性痛觉过敏、光敏感性和焦虑样行为。雌性大鼠可能更容易受到降钙素基因相关肽的影响,更好地了解降钙素基因相关肽信号的性别二态性可能有助于改善偏头痛的治疗。