Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.
Using the chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord, and identified SIP30 as a gene whose expression was elevated after CCI. SIP30 was previously shown to interact with SNAP25, but whose function was otherwise unknown. We now show that in the spinal cord, SIP30 was present in the dorsal horn laminae where the peripheral nociceptive inputs first synapse, co-localizing with nociception-related neuropeptides CGRP and substance P. With the onset of neuropathic pain after CCI surgery, SIP30 mRNA and protein levels increased in the ipsilateral side of the spinal cord, suggesting a potential association between SIP30 and neuropathic pain. When CCI-upregulated SIP30 was inhibited by intrathecal antisense oligonucleotide administration, neuropathic pain was attenuated. This neuropathic pain-reducing effect was observed both during neuropathic pain onset following CCI, and after neuropathic pain was fully established, implicating SIP30 involvement in the development and maintenance phases of neuropathic pain. Using a secretion assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of synaptic vesicles available for exocytosis, pointing to a potential function for SIP30. These results suggest a role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain.
Zhang
Yu-Qiu
YQ
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Guo
Ning
N
Peng
Guangdun
G
Wang
Xidao
X
Han
Mei
M
Raincrow
Jeremy
J
Chiu
Chi-hua
CH
Coolen
Lique M
LM
Wenthold
Robert J
RJ
Zhao
Zhi-Qi
ZQ
Jing
Naihe
N
Yu
Lei
L
D000818:Animals; D015153:Blotting, Western; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology*; D002908:Chronic Disease; D003251:Constriction, Pathologic; D005089:Exocytosis / Q000187:drug effects; D006358:Hot Temperature; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology; D010146:Pain / Q000473:pathology* / Q000523:psychology; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000473:pathology* / Q000523:psychology; D010812:Physical Stimulation; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020426:Sciatic Neuropathy / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; C459407:Zwint protein, rat; D012313:RNA