Spinal Dynorphin and Bradykinin Receptors Maintain Inflammatory Hyperalgesia

Miaw Chyi Luo, Qingmin Chen, Michael H. Ossipov, David R. Rankin, Frank Porreca, Josephine Lai

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

An upregulation of the endogenous opioid, dynorphin A, in the spinal cord is seen in multiple experimental models of chronic pain. Recent findings implicate a direct excitatory action of dynorphin A at bradykinin receptors to promote hyperalgesia in nerve injured rats, and its upregulation may promote, rather than counteract, enhanced nociceptive input due to injury. Here we examined a model of inflammatory pain by unilateral injection of complete Freund's adjuvant (CFA) into the rat hind paw. Rats exhibited tactile hypersensitivity and thermal hyperalgesia in the inflamed paw by 6 hours after CFA injection, whereas a significant elevation of prodynorphin transcripts in the lumbar spinal cord was seen at day 3 but not at 6 hours. Thermal hyperalgesia at day 3, but not at 6 hours, after CFA injection was blocked by intrathecal administration of anti-dynorphin antiserum or by bradykinin receptor antagonists. The antihyperalgesic effect of the latter was not due to de novo production of bradykinin or upregulation of spinal bradykinin receptors. These data suggest that elevated spinal dynorphin on peripheral inflammation mediates chronic inflammatory hyperalgesia. The antihyperalgesic effect of bradykinin receptor antagonists requires the presence of upregulated spinal dynorphin but not of de novo production of bradykinin, supporting our hypothesis that pathological levels of dynorphin may activate spinal bradykinin receptors to mediate inflammatory hyperalgesia. Perspective: This study shows that chronic peripheral inflammation induces a significant upregulation of the endogenous opioid peptide dynorphin. Elevated levels of spinal dynorphin and activation of spinal bradykinin receptors are essential to maintain inflammatory hyperalgesia. The results suggest that blockade of spinal bradykinin receptors may have therapeutic potential in chronic inflammatory pain.

Original languageEnglish (US)
Pages (from-to)1096-1105
Number of pages10
JournalJournal of Pain
Volume9
Issue number12
DOIs
StatePublished - Dec 2008

Fingerprint

Bradykinin Receptors
Dynorphins
Hyperalgesia
Freund's Adjuvant
Up-Regulation
Spinal Cord
Bradykinin
Chronic Pain
Injections
Inflammation
Opioid Peptides
dynorphin receptor
Opioid Analgesics
Immune Sera
Hypersensitivity
Theoretical Models
Pain

Keywords

  • complete Freund's adjuvant
  • G protein coupled receptor
  • inflammation
  • nociceptors
  • pain
  • Spinal cord

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Neurology
  • Clinical Neurology

Cite this

Spinal Dynorphin and Bradykinin Receptors Maintain Inflammatory Hyperalgesia. / Luo, Miaw Chyi; Chen, Qingmin; Ossipov, Michael H.; Rankin, David R.; Porreca, Frank; Lai, Josephine.

In: Journal of Pain, Vol. 9, No. 12, 12.2008, p. 1096-1105.

Research output: Contribution to journalArticle

Luo, Miaw Chyi ; Chen, Qingmin ; Ossipov, Michael H. ; Rankin, David R. ; Porreca, Frank ; Lai, Josephine. / Spinal Dynorphin and Bradykinin Receptors Maintain Inflammatory Hyperalgesia. In: Journal of Pain. 2008 ; Vol. 9, No. 12. pp. 1096-1105.
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