Mechanical allodynia induced by optogenetic sensory nerve excitation activates dopamine signaling and metabolism in medial nucleus accumbens

Eiji Sugiyama, Takashige Kondo, Naoko Kuzumaki, Kurara Honda, Akihiro Yamanaka, Minoru Narita, Makoto Suematsu, Yuki Sugiura

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The mesolimbic dopaminergic signaling, such as that originating from the ventral tegmental area (VTA) neurons in the medial part of the nucleus accumbens (mNAc), plays a role in complex sensory and affective components of pain. To date, we have demonstrated that optogenetic sensory nerve stimulation rapidly alters the dopamine (DA) content within the mNAc. However, the physiological role and biochemical processes underlying such rapid and regional dynamics of DA remain unclear. In this study, using imaging mass spectrometry (IMS), we observed that sensitized pain stimulation by optogenetic sensory nerve activation increased DA and 3-Methoxytyramine (3-MT; a post-synaptic metabolite obtained following DA degradation) in the mNAc of the experimental mice. To delineate the mechanism associated with elevation of DA and 3-MT, the de novo synthesized DA in the VTA/substantia nigra terminal areas was evaluated using IMS by visualizing the metabolic conversion of stable isotope-labeled tyrosine (13C15N-Tyr) to DA. Our approach revealed that at steady state, the de novo synthesized DA occupied >10% of the non-labeled DA pool in the NAc within 1.5 h of isotope-labeled Tyr administration, despite no significant increase following pain stimulation. These results suggested that sensitized pain triggered an increase in the release and postsynaptic intake of DA in the mNAc, followed by its degradation, and likely delayed de novo DA synthesis. In conclusion, we demonstrated that short, peripheral nerve excitation with mechanical stimulation accelerates the mNAc-specific DA signaling and metabolism which might be associated with the development of mechanical allodynia.

Original languageEnglish
Article number104494
JournalNeurochemistry International
Volume129
DOIs
Publication statusPublished - 2019 Oct 1

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Optogenetics
Hyperalgesia
Nucleus Accumbens
Dopamine
Pain
Ventral Tegmental Area
Isotopes
Mass Spectrometry
Biochemical Phenomena
Physiological Phenomena
Substantia Nigra
Peripheral Nerves

Keywords

  • Dopamine
  • Imaging mass spectrometry
  • Mechanical allodynia
  • Nucleus accumbens
  • Optogenetics
  • Ventral tegmental area

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Mechanical allodynia induced by optogenetic sensory nerve excitation activates dopamine signaling and metabolism in medial nucleus accumbens. / Sugiyama, Eiji; Kondo, Takashige; Kuzumaki, Naoko; Honda, Kurara; Yamanaka, Akihiro; Narita, Minoru; Suematsu, Makoto; Sugiura, Yuki.

In: Neurochemistry International, Vol. 129, 104494, 01.10.2019.

Research output: Contribution to journalArticle

Sugiyama, Eiji ; Kondo, Takashige ; Kuzumaki, Naoko ; Honda, Kurara ; Yamanaka, Akihiro ; Narita, Minoru ; Suematsu, Makoto ; Sugiura, Yuki. / Mechanical allodynia induced by optogenetic sensory nerve excitation activates dopamine signaling and metabolism in medial nucleus accumbens. In: Neurochemistry International. 2019 ; Vol. 129.
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abstract = "The mesolimbic dopaminergic signaling, such as that originating from the ventral tegmental area (VTA) neurons in the medial part of the nucleus accumbens (mNAc), plays a role in complex sensory and affective components of pain. To date, we have demonstrated that optogenetic sensory nerve stimulation rapidly alters the dopamine (DA) content within the mNAc. However, the physiological role and biochemical processes underlying such rapid and regional dynamics of DA remain unclear. In this study, using imaging mass spectrometry (IMS), we observed that sensitized pain stimulation by optogenetic sensory nerve activation increased DA and 3-Methoxytyramine (3-MT; a post-synaptic metabolite obtained following DA degradation) in the mNAc of the experimental mice. To delineate the mechanism associated with elevation of DA and 3-MT, the de novo synthesized DA in the VTA/substantia nigra terminal areas was evaluated using IMS by visualizing the metabolic conversion of stable isotope-labeled tyrosine (13C15N-Tyr) to DA. Our approach revealed that at steady state, the de novo synthesized DA occupied >10{\%} of the non-labeled DA pool in the NAc within 1.5 h of isotope-labeled Tyr administration, despite no significant increase following pain stimulation. These results suggested that sensitized pain triggered an increase in the release and postsynaptic intake of DA in the mNAc, followed by its degradation, and likely delayed de novo DA synthesis. In conclusion, we demonstrated that short, peripheral nerve excitation with mechanical stimulation accelerates the mNAc-specific DA signaling and metabolism which might be associated with the development of mechanical allodynia.",
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