Agrin downregulation induced by nerve injury contributes to neuropathic pain

Jian Guo Cui, Nicolas G. Bazan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The elusiveness of neuropathic pain mechanisms is a major impediment in developing effective clinical treatments. Here we show that peripheral nerve injury decreased agrin expression in the ipsilateral spinal dorsal horn of rats displaying tactile allodynia. SCP1, an acetaminophen analog, suppressed allodynia and promoted agrin upregulation. Preemptive treatment with SCP1 also upregulated agrin, thereby preventing neuropathic pain development. Expression of 50 kDa agrin delivered by adeno-associated virus into the dorsal horn also suppressed allodynia and hyperalgesia. Allodynia suppression was a consequence of serine residue 896/897 phosphorylation of NMDA receptor NR1 subunits in the GABA interneurons of the dorsal horn. Agrin silencing by small interference RNA, administered with either AAV-Ag50 vector or SCP1, blocked allodynia suppression, agrin upregulation, and NR1 phosphorylation. In conclusion, 50 kDa agrin modulates neuropathic pain through NR1 phosphorylation in GABA neurons. This mechanism may open new approaches for treating not only neuropathic pain, but also epilepsy, tremors, and spasticity.

Original languageEnglish
Pages (from-to)15286-15297
Number of pages12
JournalJournal of Neuroscience
Volume30
Issue number45
DOIs
StatePublished - Nov 10 2010

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Agrin
Neuralgia
Hyperalgesia
Down-Regulation
Wounds and Injuries
Phosphorylation
Up-Regulation
GABAergic Neurons
Peripheral Nerve Injuries
Dependovirus
Tremor
Interneurons
Acetaminophen
RNA Interference
gamma-Aminobutyric Acid
Serine
Epilepsy

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Agrin downregulation induced by nerve injury contributes to neuropathic pain. / Cui, Jian Guo; Bazan, Nicolas G.

In: Journal of Neuroscience, Vol. 30, No. 45, 10.11.2010, p. 15286-15297.

Research output: Contribution to journalArticle

Cui, Jian Guo ; Bazan, Nicolas G. / Agrin downregulation induced by nerve injury contributes to neuropathic pain. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 45. pp. 15286-15297.
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