Attenuation of persistent experimental pancreatitis pain by a bradykinin B2 receptor antagonist

Qingmin Chen, Louis P. Vera-Portocarrero, Michael H. Ossipov, Marina Vardanyan, Josephine Lai, Frank Porreca

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective: The role of bradykinin (BK) receptors in activating and sensitizing peripheral nociceptors is well known. Recently, we showed that spinal dynorphin was pronociceptive through direct or indirect BK receptor activation. Here, we explored the potential role of BK receptors in pain associated with persistent pancreatitis in rats. Methods: Experimental pancreatitis and abdominal hypersensitivity were induced by intravenous administrations of dibutyltin dichloride (DBTC). [des-Arg9-Leu 8]BK (B1 antagonist) and HOE 140 (B2 antagonist) were given by intraperitoneal or intrathecal injection. Dynorphin antiserum was given intrathecally. Reverse transcription-polymerase chain reaction was used to detect spinal mRNA for BK receptors. Results: Dibutyltin dichloride-induced pancreatitis upregulated B1 and B2 mRNA in the thoracic dorsal root ganglion and B2, but not B1, in the pancreas. No changes in spinal B1 or B2 mRNA were observed. Intraperitoneal or intrathecal administration of HOE 140 dose dependently abolished DBTC-induced abdominal hypersensitivity, whereas [des-Arg9-Leu8]BK was without effect by either route of administration. Antiserum to dynorphin (intrathecal) abolished DBTC-induced hypersensitivity. Conclusions: These results suggest that blockade of peripheral or spinal BK B2 receptors may be an effective approach for diminishing pain associated with pancreatitis. Moreover, it is suggested that spinal dynorphin may maintain pancreatitis pain through direct or indirect activation of BK B2 receptors in the spinal cord.

Original languageEnglish (US)
Pages (from-to)1220-1225
Number of pages6
JournalPancreas
Volume39
Issue number8
DOIs
StatePublished - Nov 1 2010

    Fingerprint

Keywords

  • bradykinin receptor
  • bradykinin receptor antagonists
  • pancreatitis pain

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this