Group II metabotropic glutamate receptor activation on peripheral nociceptors modulates TRPV1 function

Susan M. Carlton, Junhui Du, Shengtai Zhou

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Transient receptor potential vanilloid 1 (TRPV1) receptors are critical to nociceptive processing. Understanding how these receptors are modulated gives insight to potential therapies for pain. We demonstrate using double labeling immunohistochemistry that Group II metabotropic glutamate receptors (mGluRs) are co-expressed with TRPV1 on rat dorsal root ganglion (DRG) cells. In behavioral studies, intraplantar 0.1 μM APDC, a group II agonist, significantly attenuates capsaicin-induced nociceptive behaviors through a local effect. The APDC-induced inhibition of capsaicin responses is blocked by 1 μM LY341495, a group II antagonist. At the single fiber level, nociceptor responses to capsaicin are significantly decreased following exposure to APDC and this effect is blocked by LY341495. Finally, activation of peripheral group II mGluRs inhibits forskolin-induced thermal hyperalgesia and nociceptor heat sensitization, suggesting group II receptors are negatively coupled to the cAMP/PKA pathway. The data indicate that group II mGluRs and TRPV1 receptors are co-expressed on peripheral nociceptors and activation of mGluRs can inhibit painful sensory transmission following TRPV1 activation. The data are consistent with group II and TRPV1 receptors being linked intracellularly by the cAMP/PKA pathway. Peripheral group II mGluRs are important targets for drug discovery in controlling TRPV1-induced nociception.

Original languageEnglish (US)
Pages (from-to)86-95
Number of pages10
JournalBrain Research
Volume1248
DOIs
StatePublished - Jan 12 2009

Fingerprint

Nociceptors
Metabotropic Glutamate Receptors
Capsaicin
LY 341495
Nociception
Hyperalgesia
Spinal Ganglia
Colforsin
Drug Discovery
vanilloid receptor subtype 1
Hot Temperature
Immunohistochemistry
Pain

Keywords

  • APDC
  • Capsaicin
  • LY341495
  • mGluR
  • Pain
  • Primary afferent
  • Sensitization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Group II metabotropic glutamate receptor activation on peripheral nociceptors modulates TRPV1 function. / Carlton, Susan M.; Du, Junhui; Zhou, Shengtai.

In: Brain Research, Vol. 1248, 12.01.2009, p. 86-95.

Research output: Contribution to journalArticle

Carlton, Susan M. ; Du, Junhui ; Zhou, Shengtai. / Group II metabotropic glutamate receptor activation on peripheral nociceptors modulates TRPV1 function. In: Brain Research. 2009 ; Vol. 1248. pp. 86-95.
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