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Modulatory role of neuropeptide FF system in nociception and opiate analgesia

Hsiu-Ying T Yang1, Tao Tao, Michael J Iadarola

  • 1Neurobiology and Pain Therapeutics Section, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD 20892-4410, USA. hyang@dir.nidcr.nih.gov

Neuropeptides
|September 15, 2007
PubMed

Insights

Neuropeptide FF (NPFF) and its receptor NPFF-R2 are involved in pain modulation. Their expression and regulation in the spinal cord suggest a role in inflammatory pain and opiate analgesia.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • The tetra-peptide FMRF-NH(2), a cardioexcitatory peptide in clams, has analogs detected in the mammalian central nervous system (CNS).
  • Mammalian FMRF-NH(2)-like peptides, including Neuropeptide FF (NPFF) and NPAF, have been isolated and characterized.
  • The NPFF system, including precursor proteins and receptors (NPFFR1, NPFFR2), is highly conserved across vertebrates.

Purpose of the Study:

  • To investigate the biological roles of the NPFF system, particularly its modulatory effects on nociception and opiate analgesia.
  • To explore the potential involvement of NPFF in pain modulation through acid-sensing ion channels (ASICs).
  • To examine the expression and regulation of NPFF and NPFF-R2 in the rat CNS, especially in the context of inflammation.

Main Methods:

  • Immunohistochemistry using antibodies against FMRF-NH(2) to detect immunoreactive material in the mammalian CNS.
  • Isolation and characterization of mammalian FMRF-NH(2)-like peptides from bovine brain.
  • Pharmacological studies investigating the effects of NPFF-related peptides on analgesia and opiate activity.
  • Analysis of gene expression (mRNA) for NPFF and NPFF-R2 in rat spinal cord and dorsal root ganglia (DRG).
  • Assessment of NPFF-R2 immunoreactivity in primary afferents under conditions of peripheral inflammation.

Main Results:

  • NPFF-related peptides were found to exhibit analgesic properties and modulate opiate-induced analgesia differently depending on administration route (intrathecal vs. intracerebroventricular).
  • NPFF peptides were shown to delay ASIC desensitization, enhancing acid-gated currents, suggesting a potential pain modulatory role via ASICs.
  • NPFF and NPFF-R2 genes are highly expressed in the superficial layers of the dorsal spinal cord and DRG.
  • Peripheral inflammation led to coordinate up-regulation of NPFF and NPFF-R2 mRNAs in the spinal cord and DRG, with increased NPFF-R2 immunoreactivity in primary afferents.

Conclusions:

  • The NPFF system plays a significant role in pain modulation, evidenced by its analgesic and opiate-modulating activities.
  • NPFF's interaction with ASICs offers a novel mechanism for its pain modulatory function.
  • The observed regulation of NPFF and NPFF-R2 expression and localization in response to inflammation strongly supports their involvement in pain processing and the inflammatory pain state.

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