Effects of Intrathecal Administration of Prostaglandin-D2 on Stress-Induced Analgesia: Involvements of DP2 Receptors

IF 0.5 4区 医学 Q4 NEUROSCIENCES
Mona Paknia, Mohammad Zarei, Safoura Raoufi, Parisa Habibi, Fatemeh Ramezani‑Aliakbari, Seyed Asaad Karimi
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Abstract

Prostaglandin D2 is the most abundant prostaglandin in the mammalian brain. Exposure to stressful stimuli is often accompanied by reduced pain sensitivity, termed “stress-induced analgesia” (SIA). In the present study, the possible modulatory role of prostaglandin-D2 (PGD2) in the acute or chronic type of SIA was examined in male and female rats. Acute and chronic (long-term) restraint stress (RS) in male and female rats was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. The involvements of specific PGD2 receptors in the modulatory role of PGD2 on SIA also investigated by specific antagonists (DP1 or DP2). Corticosterone levels were assessed in groups of rats following exposure to stress. Acute or chronic restraint stress altered formalin-induced spontaneous behaviors in male and female rats. Furthermore, intrathecal microinjection of PGD2 (10 µg/mL) could reverse acute SIA in male but not in female rats. DP2 antagonist of PGD2 (CAY10471) attenuated pain score in the acute RS-induced analgesia in male rats. Administration of PGD2 increases the phospho-extracellular signal regulated kinase 2 (pERK2) levels in the spinal cord of male RS rats. Sex differences were also seen in plasma corticosterone concentrations post injection of PGD2 in acute SIA in male rats. The outcome suggests that not only central microinjection of PGD2 could attenuate acute SIA in male rats, but also its antagonist could turn over this effect.

Abstract Image

鞘内注射前列腺素-D2 对应激诱导镇痛的影响:DP2 受体的参与
摘要前列腺素D2是哺乳动物大脑中最丰富的前列腺素。暴露于应激性刺激时,疼痛敏感性通常会降低,这被称为 "应激诱导镇痛"(SIA)。本研究以雄性和雌性大鼠为研究对象,探讨了前列腺素-D2(PGD2)在急性或慢性 SIA 中可能发挥的调节作用。在对雌雄大鼠进行急性和慢性(长期)束缚应激(RS)之前,先对其进行跖内注射福尔马林(一种有害的炎症制剂)。还通过特定的拮抗剂(DP1或DP2)研究了特定PGD2受体在PGD2对SIA的调节作用中的参与情况。在暴露于应激后,对各组大鼠的皮质酮水平进行了评估。急性或慢性束缚应激改变了福尔马林诱导的雌雄大鼠的自发行为。此外,鞘内微量注射 PGD2(10 µg/mL)可逆转雄性大鼠的急性 SIA,但不能逆转雌性大鼠的急性 SIA。PGD2的DP2拮抗剂(CAY10471)可减轻雄性大鼠在急性RS诱导镇痛中的疼痛评分。给予 PGD2 会增加雄性 RS 大鼠脊髓中磷酸胞外信号调节激酶 2(pERK2)的水平。注射 PGD2 后,雄性大鼠急性 SIA 的血浆皮质酮浓度也出现了性别差异。研究结果表明,不仅中枢微量注射 PGD2 可以减轻雄性大鼠急性 SIA 的症状,而且其拮抗剂也可以扭转这种效应。
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来源期刊
Neurochemical Journal
Neurochemical Journal 医学-神经科学
自引率
20.00%
发文量
40
审稿时长
>12 weeks
期刊介绍: Neurochemical Journal (Neirokhimiya) provides a source for the communication of the latest findings in all areas of contemporary neurochemistry and other fields of relevance (including molecular biology, biochemistry, physiology, neuroimmunology, pharmacology) in an afford to expand our understanding of the functions of the nervous system. The journal presents papers on functional neurochemistry, nervous system receptors, neurotransmitters, myelin, chromaffin granules and other components of the nervous system, as well as neurophysiological and clinical aspects, behavioral reactions, etc. Relevant topics include structure and function of the nervous system proteins, neuropeptides, nucleic acids, nucleotides, lipids, and other biologically active components. The journal is devoted to the rapid publication of regular papers containing the results of original research, reviews highlighting major developments in neurochemistry, short communications, new experimental studies that use neurochemical methodology, descriptions of new methods of value for neurochemistry, theoretical material suggesting novel principles and approaches to neurochemical problems, presentations of new hypotheses and significant findings, discussions, chronicles of congresses, meetings, and conferences with short presentations of the most sensational and timely reports, information on the activity of the Russian and International Neurochemical Societies, as well as advertisements of reagents and equipment.
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