The Korean Journal of Pain

  • 제34권1호
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  • Pages.27-34
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  • 2021
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  • 2005-9159(pISSN)
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  • 2093-0569(eISSN)
대한통증학회 (The Korean Pain Society)
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Prostaglandin D2 contributes to cisplatin-induced neuropathic pain in rats via DP2 receptor in the spinal cord

  • Li, Yaqun (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Kim, Woong Mo (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Kim, Seung Hoon (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • You, Hyun Eung (Department of Anesthesiology and Pain Medicine, Chonnam National University Hwasun Hospital) ;
  • Kang, Dong Ho (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Lee, Hyung Gon (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Choi, Jeong Il (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Yoon, Myung Ha (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School)
  • 투고 : 2020.09.18
  • 심사 : 2020.10.28
  • 발행 : 2021.01.01
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초록

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomechanisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2) signaling in cisplatin-induced neuropathic pain. Methods: CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting. Results: The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001). Conclusions: The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.

키워드

과제정보

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A3B07050259).

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