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Mu and delta opioid receptors on nociceptors attenuate mechanical hyperalgesia in rat

E K Joseph1, J D Levine

  • 1Division of Neuroscience, Department of Medicine, University of California, San Francisco, CA 94143, USA.

Neuroscience
|August 26, 2010
PubMed

Insights

This study reveals that delta-opioid receptor (DOR) agonists inhibit glia-derived growth factor (GDNF)-induced pain sensitization, while both mu-opioid receptor (MOR) and DOR agonists target nerve growth factor (NGF)-sensitive pain pathways.

Area of Science:

  • Neuroscience
  • Pain Research
  • Pharmacology

Background:

  • Mechanical hyperalgesia is a key feature of many pain conditions.
  • Nociceptors, sensory neurons transmitting pain, are crucial in developing hyperalgesia.
  • Opioid receptors, specifically mu-opioid receptor (MOR) and delta-opioid receptor (DOR), are targets for pain management.

Purpose of the Study:

  • To investigate the specific nociceptor populations involved in mechanical hyperalgesia.
  • To determine the role of MOR and DOR agonists in inhibiting hyperalgesia induced by different factors.
  • To explore the potential for combined MOR and DOR agonist therapy for enhanced analgesia.

Main Methods:

  • Induction of mechanical hyperalgesia using glia-derived growth factor (GDNF) and nerve growth factor (NGF) in rats.
  • Administration of MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) and DOR agonist SNC.
  • Selective ablation of isolectin B4 (IB4)-binding neurons using IB4-saporin to identify specific nociceptor roles.

Main Results:

  • Both GDNF and NGF induced mechanical hyperalgesia via distinct nociceptor populations.
  • DOR agonist SNC, but not MOR agonist DAMGO, inhibited GDNF-induced hyperalgesia.
  • Both DAMGO and SNC inhibited NGF-induced hyperalgesia, irrespective of IB4-binding neuron presence.
  • Co-administration of DAMGO and SNC enhanced analgesia, but repeated DAMGO led to cross-tolerance to SNC.

Conclusions:

  • Most nociceptors contribute to mechanical hyperalgesia.
  • GDNF-induced hyperalgesia is selectively inhibited by DOR agonists.
  • MOR and DOR are co-localized on TrkA-positive nociceptors, mediating NGF-induced hyperalgesia.
  • Combined MOR and DOR activation shows potential for analgesia, but tolerance requires further investigation.

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