PT  - JOURNAL ARTICLE
AU  - Jian-Guo Cui
AU  - Nicolas G. Bazan
TI  - Agrin Downregulation Induced by Nerve Injury Contributes to Neuropathic Pain
AID  - 10.1523/JNEUROSCI.4418-10.2010
DP  - 2010 Nov 10
TA  - The Journal of Neuroscience
PG  - 15286--15297
VI  - 30
IP  - 45
4099  - http://www.jneurosci.org/content/30/45/15286.short
4100  - http://www.jneurosci.org/content/30/45/15286.full
SO  - J. Neurosci.2010 Nov 10; 30
AB  - 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.