Peripheral delta opioid receptors require priming for functional competence in vivo

Matthew P. Rowan, Nikita B. Ruparel, Amol M Patwardhan, Kelly A. Berg, William P. Clarke, Kenneth M. Hargreaves

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Although centrally acting opioid analgesics produce profound antinociception under basal conditions, the antinociceptive properties of peripherally restricted opioid analgesics are generally only detectable after inflammation or injection of inflammatory mediators. Despite considerable research, the cellular mechanisms regulating the functional competence of peripheral opioid receptor systems for inhibition of nociception remain unclear. Recent work has demonstrated that brief pre-treatment (priming) with bradykinin, arachidonic acid, protease-activated receptor-2 agonists, or direct activators of protein kinase C (PKC) are capable of inducing the functional competence of the opioid receptor system in cultures of primary sensory neurons in vitro. Here we report that the peripheral delta opioid receptor system also requires PKC-dependent priming to inhibit prostaglandin E2 (PGE2)-induced thermal allodynia in the rat. Peripheral hindpaw injection of [D-Pen2,5]-enkephalin (DPDPE), a selective delta opioid receptor agonist, did not alter PGE2-induced thermal allodynia. However, following priming (15 min) with bradykinin or arachidonic acid, DPDPE produced a significant reduction in allodynia that was antagonist reversible, peripherally restricted, and exhibited a typical dose-response relationship. Furthermore, the bradykinin priming effect was blocked by the PKC inhibitors, bisindolylmaleimide I and chelerythrine. Collectively, these data support prior in vitro findings that, although present on primary sensory neurons, peripheral opioid receptor systems are functionally inactive under basal conditions and require activation of a PKC- and arachidonic acid-dependent signaling pathway to develop functional competence in vivo.

Original languageEnglish (US)
Pages (from-to)283-287
Number of pages5
JournalEuropean Journal of Pharmacology
Volume602
Issue number2-3
DOIs
StatePublished - Jan 14 2009
Externally publishedYes

Fingerprint

delta Opioid Receptor
Mental Competency
Protein Kinase C
Hyperalgesia
Opioid Receptors
Bradykinin
Arachidonic Acid
D-Penicillamine (2,5)-Enkephalin
Sensory Receptor Cells
Dinoprostone
Opioid Analgesics
PAR-2 Receptor
Injections
Nociception
Protein C Inhibitor
Enkephalins
Protein Kinase Inhibitors
Inflammation
Research
In Vitro Techniques

Keywords

  • Allodynia
  • Bradykinin
  • DPDPE
  • Hindpaw
  • Prostaglandin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Peripheral delta opioid receptors require priming for functional competence in vivo. / Rowan, Matthew P.; Ruparel, Nikita B.; Patwardhan, Amol M; Berg, Kelly A.; Clarke, William P.; Hargreaves, Kenneth M.

In: European Journal of Pharmacology, Vol. 602, No. 2-3, 14.01.2009, p. 283-287.

Research output: Contribution to journalArticle

Rowan, Matthew P. ; Ruparel, Nikita B. ; Patwardhan, Amol M ; Berg, Kelly A. ; Clarke, William P. ; Hargreaves, Kenneth M. / Peripheral delta opioid receptors require priming for functional competence in vivo. In: European Journal of Pharmacology. 2009 ; Vol. 602, No. 2-3. pp. 283-287.
@article{aecb78e62ce148ed8d1eaaa1248af52f,
title = "Peripheral delta opioid receptors require priming for functional competence in vivo",
abstract = "Although centrally acting opioid analgesics produce profound antinociception under basal conditions, the antinociceptive properties of peripherally restricted opioid analgesics are generally only detectable after inflammation or injection of inflammatory mediators. Despite considerable research, the cellular mechanisms regulating the functional competence of peripheral opioid receptor systems for inhibition of nociception remain unclear. Recent work has demonstrated that brief pre-treatment (priming) with bradykinin, arachidonic acid, protease-activated receptor-2 agonists, or direct activators of protein kinase C (PKC) are capable of inducing the functional competence of the opioid receptor system in cultures of primary sensory neurons in vitro. Here we report that the peripheral delta opioid receptor system also requires PKC-dependent priming to inhibit prostaglandin E2 (PGE2)-induced thermal allodynia in the rat. Peripheral hindpaw injection of [D-Pen2,5]-enkephalin (DPDPE), a selective delta opioid receptor agonist, did not alter PGE2-induced thermal allodynia. However, following priming (15 min) with bradykinin or arachidonic acid, DPDPE produced a significant reduction in allodynia that was antagonist reversible, peripherally restricted, and exhibited a typical dose-response relationship. Furthermore, the bradykinin priming effect was blocked by the PKC inhibitors, bisindolylmaleimide I and chelerythrine. Collectively, these data support prior in vitro findings that, although present on primary sensory neurons, peripheral opioid receptor systems are functionally inactive under basal conditions and require activation of a PKC- and arachidonic acid-dependent signaling pathway to develop functional competence in vivo.",
keywords = "Allodynia, Bradykinin, DPDPE, Hindpaw, Prostaglandin",
author = "Rowan, {Matthew P.} and Ruparel, {Nikita B.} and Patwardhan, {Amol M} and Berg, {Kelly A.} and Clarke, {William P.} and Hargreaves, {Kenneth M.}",
year = "2009",
month = "1",
day = "14",
doi = "10.1016/j.ejphar.2008.11.028",
language = "English (US)",
volume = "602",
pages = "283--287",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Peripheral delta opioid receptors require priming for functional competence in vivo

AU - Rowan, Matthew P.

AU - Ruparel, Nikita B.

AU - Patwardhan, Amol M

AU - Berg, Kelly A.

AU - Clarke, William P.

AU - Hargreaves, Kenneth M.

PY - 2009/1/14

Y1 - 2009/1/14

N2 - Although centrally acting opioid analgesics produce profound antinociception under basal conditions, the antinociceptive properties of peripherally restricted opioid analgesics are generally only detectable after inflammation or injection of inflammatory mediators. Despite considerable research, the cellular mechanisms regulating the functional competence of peripheral opioid receptor systems for inhibition of nociception remain unclear. Recent work has demonstrated that brief pre-treatment (priming) with bradykinin, arachidonic acid, protease-activated receptor-2 agonists, or direct activators of protein kinase C (PKC) are capable of inducing the functional competence of the opioid receptor system in cultures of primary sensory neurons in vitro. Here we report that the peripheral delta opioid receptor system also requires PKC-dependent priming to inhibit prostaglandin E2 (PGE2)-induced thermal allodynia in the rat. Peripheral hindpaw injection of [D-Pen2,5]-enkephalin (DPDPE), a selective delta opioid receptor agonist, did not alter PGE2-induced thermal allodynia. However, following priming (15 min) with bradykinin or arachidonic acid, DPDPE produced a significant reduction in allodynia that was antagonist reversible, peripherally restricted, and exhibited a typical dose-response relationship. Furthermore, the bradykinin priming effect was blocked by the PKC inhibitors, bisindolylmaleimide I and chelerythrine. Collectively, these data support prior in vitro findings that, although present on primary sensory neurons, peripheral opioid receptor systems are functionally inactive under basal conditions and require activation of a PKC- and arachidonic acid-dependent signaling pathway to develop functional competence in vivo.

AB - Although centrally acting opioid analgesics produce profound antinociception under basal conditions, the antinociceptive properties of peripherally restricted opioid analgesics are generally only detectable after inflammation or injection of inflammatory mediators. Despite considerable research, the cellular mechanisms regulating the functional competence of peripheral opioid receptor systems for inhibition of nociception remain unclear. Recent work has demonstrated that brief pre-treatment (priming) with bradykinin, arachidonic acid, protease-activated receptor-2 agonists, or direct activators of protein kinase C (PKC) are capable of inducing the functional competence of the opioid receptor system in cultures of primary sensory neurons in vitro. Here we report that the peripheral delta opioid receptor system also requires PKC-dependent priming to inhibit prostaglandin E2 (PGE2)-induced thermal allodynia in the rat. Peripheral hindpaw injection of [D-Pen2,5]-enkephalin (DPDPE), a selective delta opioid receptor agonist, did not alter PGE2-induced thermal allodynia. However, following priming (15 min) with bradykinin or arachidonic acid, DPDPE produced a significant reduction in allodynia that was antagonist reversible, peripherally restricted, and exhibited a typical dose-response relationship. Furthermore, the bradykinin priming effect was blocked by the PKC inhibitors, bisindolylmaleimide I and chelerythrine. Collectively, these data support prior in vitro findings that, although present on primary sensory neurons, peripheral opioid receptor systems are functionally inactive under basal conditions and require activation of a PKC- and arachidonic acid-dependent signaling pathway to develop functional competence in vivo.

KW - Allodynia

KW - Bradykinin

KW - DPDPE

KW - Hindpaw

KW - Prostaglandin

UR - http://www.scopus.com/inward/record.url?scp=58149159544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149159544&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2008.11.028

DO - 10.1016/j.ejphar.2008.11.028

M3 - Article

C2 - 19063879

AN - SCOPUS:58149159544

VL - 602

SP - 283

EP - 287

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 2-3

ER -