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Rapid modulation of micro-opioid receptor signaling in primary sensory neurons

Kelly A Berg1, Amol M Patwardhan, Teresa A Sanchez

  • 1Department of Pharmacology, MS 7764, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

The Journal of Pharmacology and Experimental Therapeutics
|March 10, 2007
PubMed

Insights

Peripheral opioid analgesics show limited effects due to central side effects. This study reveals bradykinin priming enhances micro-opioid receptor signaling in sensory neurons via a cyclooxygenase-dependent pathway.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Management

Background:

  • Opioid analgesics are limited by central adverse effects, necessitating research into peripheral actions.
  • Understanding peripheral opioid effects on sensory neurons is crucial for pain management.
  • Opioid agonists typically show minimal effects on cultured nociceptors despite receptor presence.

Purpose of the Study:

  • To investigate the mechanisms underlying opioid receptor signaling in peripheral sensory neurons.
  • To explore how bradykinin (BK) influences micro-opioid receptor (MOR) agonist activity.
  • To elucidate the signaling pathways involved in enhanced MOR responsiveness.

Main Methods:

  • Primary cultures of rat trigeminal ganglion (TG) neurons were used.
  • Micro-opioid receptor agonist [D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin (DAMGO) was applied.
  • Guanosine 5'-O-(3-[(35)S]thio)-triphosphate (GTPγ[35S]) binding, adenylyl cyclase activity, and neuropeptide release were measured.
  • Effects of bradykinin (BK), receptor antagonists, and signaling pathway activators/inhibitors were assessed.

Main Results:

  • DAMGO alone did not affect basal GTPγ[35S] binding, adenylyl cyclase, or neuropeptide release.
  • Brief BK exposure potentiated DAMGO-stimulated GTPγ[35S] binding.
  • BK priming inhibited prostaglandin E(2) (PGE(2))-stimulated adenylyl cyclase and BK/PGE(2)-stimulated neuropeptide release.
  • BK's effects involved B(2) receptors, protein kinase C (PKC), and cyclooxygenase (COX) dependent arachidonic acid (AA) metabolites.

Conclusions:

  • Micro-opioid receptor signaling in TG neurons is enhanced by BK priming.
  • This enhancement is mediated by a COX-dependent AA metabolite downstream of PKC.
  • Findings suggest novel pathways for modulating peripheral opioid efficacy in pain relief.

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