Dynorphin A activates bradykinin receptors to maintain neuropathic pain

Josephine Lai, Miaw Chyi Luo, Qingmin Chen, Shouwu Ma, Luis R. Gardell, Michael H. Ossipov, Frank Porreca

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Dynorphin A is an endogenous opioid peptide that produces non-opioid receptor-mediated neural excitation. Here we demonstrate that dynorphin induces calcium influx via voltage-sensitive calcium channels in sensory neurons by activating bradykinin receptors. This action of dynorphin at bradykinin receptors is distinct from the primary signaling pathway activated by bradykinin and underlies the hyperalgesia produced by pharmacological administration of dynorphin by the spinal route in rats and mice. Blockade of spinal B1 or B2 receptor also reverses persistent neuropathic pain but only when there is sustained elevation of endogenous spinal dynorphin, which is required for maintenance of neuropathic pain. These data reveal a mechanism for endogenous dynorphin to promote pain through its agonist action at bradykinin receptors and suggest new avenues for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)1534-1540
Number of pages7
JournalNature Neuroscience
Volume9
Issue number12
DOIs
StatePublished - Dec 2006

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Bradykinin Receptors
Dynorphins
Neuralgia
Sensory Receptor Cells
Opioid Peptides
Hyperalgesia
Bradykinin
Calcium Channels
Maintenance
Pharmacology
Calcium
Pain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lai, J., Luo, M. C., Chen, Q., Ma, S., Gardell, L. R., Ossipov, M. H., & Porreca, F. (2006). Dynorphin A activates bradykinin receptors to maintain neuropathic pain. Nature Neuroscience, 9(12), 1534-1540. https://doi.org/10.1038/nn1804

Dynorphin A activates bradykinin receptors to maintain neuropathic pain. / Lai, Josephine; Luo, Miaw Chyi; Chen, Qingmin; Ma, Shouwu; Gardell, Luis R.; Ossipov, Michael H.; Porreca, Frank.

In: Nature Neuroscience, Vol. 9, No. 12, 12.2006, p. 1534-1540.

Research output: Contribution to journalArticle

Lai, J, Luo, MC, Chen, Q, Ma, S, Gardell, LR, Ossipov, MH & Porreca, F 2006, 'Dynorphin A activates bradykinin receptors to maintain neuropathic pain', Nature Neuroscience, vol. 9, no. 12, pp. 1534-1540. https://doi.org/10.1038/nn1804
Lai J, Luo MC, Chen Q, Ma S, Gardell LR, Ossipov MH et al. Dynorphin A activates bradykinin receptors to maintain neuropathic pain. Nature Neuroscience. 2006 Dec;9(12):1534-1540. https://doi.org/10.1038/nn1804
Lai, Josephine ; Luo, Miaw Chyi ; Chen, Qingmin ; Ma, Shouwu ; Gardell, Luis R. ; Ossipov, Michael H. ; Porreca, Frank. / Dynorphin A activates bradykinin receptors to maintain neuropathic pain. In: Nature Neuroscience. 2006 ; Vol. 9, No. 12. pp. 1534-1540.
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