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

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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.

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Funding

The study was funded by Vice-chancellor for Research and Technology at Hamadan University of Medical Sciences (No. 140004083033) and extracted from MSc Thesis.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Mona Paknia, Mohammad Zarei, Safoura Raoufi, Parisa Habibi & Fatemeh Ramezani‑Aliakbari

  2. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Mohammad Zarei, Safoura Raoufi, Parisa Habibi & Seyed Asaad Karimi

Authors
  1. Mona Paknia
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  2. Mohammad Zarei
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  3. Safoura Raoufi
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  4. Parisa Habibi
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  6. Seyed Asaad Karimi
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Contributions

Data analysis and interpretation: Mona Paknia; Data acquisition, Mohammad Zarei; Study conception, design, and critical revision. Mona Paknia, Safoura Raoufi, Parisa Habibi, Fatemeh Ramezani-Aliakbari, and Seyed Asaad Karimi; Drafting of the manuscript.

Corresponding author

Correspondence to Mohammad Zarei.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The experimentation protocols were following the instructions agreed by the NIH Publication; No. 85-23, 1985. The Ethics Committee of the University of Medical Sciences- Hamadan approved the research (Ethical No. 1397.618).

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The authors of this work declare that they have no conflicts of interest.

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Mona Paknia, Zarei, M., Raoufi, S. et al. Effects of Intrathecal Administration of Prostaglandin-D2 on Stress-Induced Analgesia: Involvements of DP2 Receptors. Neurochem. J. 18, 313–320 (2024). https://doi.org/10.1134/S1819712424020119

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