TY - JOUR
T1 - Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma
AU - Li, Zhisong
AU - Gu, Xiyao
AU - Sun, Linlin
AU - Wu, Shaogen
AU - Liang, Lingli
AU - Cao, Jing
AU - Lutz, Brianna Marie
AU - Bekker, Alex
AU - Zhang, Wei
AU - Tao, Yuan Xiang
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health, Bethesda, Maryland (NS072206, HL117684, and DA033390) and the Rita Allen Foundation, Princeton, New Jersey. Z. Li, X. Gu, L. Sun, and S. Wu contributed equally to this work. Y.-X. Tao and W. Zhang conceived the project and supervised most experiments. Z. Li, X. Gu, S. Wu, L. Sun, L. Liang, J. Cao, B. M. Lutz, A. Bekker, and Y.-X. Tao designed the project. Z. Li performed the animal model, conducted behavioral experiments, and performed microinjection. X. Gu performed electrophysiological recording. L. Sun performed Western blot and behavioral testing. S. Wu performed real-time RT-PCR. L. Liang, B. M. Lutz, and J. Cao were involved in parts of animal model conductance, behavioral testing, or microinjection. Z. Li, X. Gu, S. Wu, L. Sun, W. Zhang, and Y.-X. Tao analyzed the data. Y.-X. Tao wrote the manuscript. All of the authors read and discussed the manuscript.
Publisher Copyright:
© 2015 Lippincott Williams and Wilkins. All rights reserved.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Peripheral nerve injury induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltagegated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury induced increase of DRG MZF1 through microinjection of recombinant adeno-Associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-Triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.
AB - Peripheral nerve injury induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltagegated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury induced increase of DRG MZF1 through microinjection of recombinant adeno-Associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-Triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.
KW - Dorsal root ganglion
KW - Kv1.2 antisense RNA
KW - Kv1.2 mRNA
KW - Myeloid zinc finger protein 1
KW - Neuropathic pain
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U2 - 10.1097/j.pain.0000000000000103
DO - 10.1097/j.pain.0000000000000103
M3 - Article
C2 - 25630025
AN - SCOPUS:85003043816
SN - 0304-3959
VL - 156
SP - 711
EP - 721
JO - Pain
JF - Pain
IS - 4
ER -