Scholarlink

<p>Analgesia by non-steroidal anti-inflammatory drugs (NSAIDs) is ascribed to inhibition of prostaglandin (PG) biosynthesis and ensuing inflammation. However, NSAIDs have life-threatening side effects, and inhibition of inflammation delays pain resolution. Decoupling the mechanisms underlying PG-evoked pain <i>vs</i>. protective inflammation would facilitate pain treatment. Herein, we reveal that selective silencing of the PGE<sub>2</sub> receptor 2 (EP2) in Schwann cells via adeno-associated viral vectors abrogates the indomethacin-sensitive component of pain-like responses in mice elicited by inflammatory stimuli without affecting inflammation. In human Schwann cells and in mice, EP2 activation and optogenetic stimulation of adenylyl cyclase evokes a plasma membrane-compartmentalized cyclic adenosine monophosphate (cAMP) signal that, via A-kinase anchor protein-associated protein kinase A, sustains inflammatory pain-like responses, but does not delay their resolution. Thus, an unforeseen and druggable EP2 receptor in Schwann cells, via specific cAMP nanodomains, encodes PGE<sub>2</sub>-mediated persistent inflammatory pain but not PG-dependent protective inflammation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Targeting prostaglandin E2 receptor 2 in Schwann cells inhibits inflammatory pain but not inflammation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月25日

查看全文
  • Romina Nassini,
  • Lorenzo Landini,
  • Matilde Marini,
  • Martina Chieca,
  • Daniel Souza Monteiro de Araújo,
  • Marco Montini,
  • Pasquale Pensieri,
  • Vittorio Donato Abruzzese,
  • Gaetano De Siena,
  • Jin Zhang,
  • Elisa Bellantoni,
  • Vincenzo De Giorgi,
  • Antonia Romitelli,
  • Giulia Brancolini,
  • Raquel Tonello,
  • Chloe J. Peach,
  • Alessandra Mastricci,
  • Irene Scuffi,
  • Martina Tesi,
  • Dane D. Jensen,
  • Brian L. Schmidt,
  • Nigel W. Bunnett,
  • Francesco De Logu,
  • Pierangelo Geppetti

摘要

Analgesia by non-steroidal anti-inflammatory drugs (NSAIDs) is ascribed to inhibition of prostaglandin (PG) biosynthesis and ensuing inflammation. However, NSAIDs have life-threatening side effects, and inhibition of inflammation delays pain resolution. Decoupling the mechanisms underlying PG-evoked pain vs. protective inflammation would facilitate pain treatment. Herein, we reveal that selective silencing of the PGE2 receptor 2 (EP2) in Schwann cells via adeno-associated viral vectors abrogates the indomethacin-sensitive component of pain-like responses in mice elicited by inflammatory stimuli without affecting inflammation. In human Schwann cells and in mice, EP2 activation and optogenetic stimulation of adenylyl cyclase evokes a plasma membrane-compartmentalized cyclic adenosine monophosphate (cAMP) signal that, via A-kinase anchor protein-associated protein kinase A, sustains inflammatory pain-like responses, but does not delay their resolution. Thus, an unforeseen and druggable EP2 receptor in Schwann cells, via specific cAMP nanodomains, encodes PGE2-mediated persistent inflammatory pain but not PG-dependent protective inflammation.