Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma

Zhisong Li, Xiyao Gu, Linlin Sun, Shaogen Wu, Lingli Liang, Jing Cao, Brianna M arie Lutz, Alex Bekker, Wei Zhang, Yuan Xiang Tao

Research output: Contribution to journalArticle

Abstract

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 voltage-gated 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.

Original languageEnglish (US)
Pages (from-to)711-721
Number of pages11
JournalPain
Volume156
Issue number4
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Zinc Fingers
Spinal Ganglia
Neuralgia
Peripheral Nerves
Wounds and Injuries
Proteins
Constriction
Antisense RNA
Peripheral Nerve Injuries
Hot Temperature
Microinjections
Hypersensitivity
Transcription Factors
Pain
Dependovirus
Sensory Receptor Cells
Sciatic Nerve
Small Interfering RNA
Genes
Potassium

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma. / Li, Zhisong; Gu, Xiyao; Sun, Linlin; Wu, Shaogen; Liang, Lingli; Cao, Jing; Lutz, Brianna M arie; Bekker, Alex; Zhang, Wei; Tao, Yuan Xiang.

In: Pain, Vol. 156, No. 4, 01.04.2015, p. 711-721.

Research output: Contribution to journalArticle

Li, Z, Gu, X, Sun, L, Wu, S, Liang, L, Cao, J, Lutz, BMA, Bekker, A, Zhang, W & Tao, YX 2015, 'Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma', Pain, vol. 156, no. 4, pp. 711-721. https://doi.org/10.1097/j.pain.0000000000000103
Li, Zhisong ; Gu, Xiyao ; Sun, Linlin ; Wu, Shaogen ; Liang, Lingli ; Cao, Jing ; Lutz, Brianna M arie ; Bekker, Alex ; Zhang, Wei ; Tao, Yuan Xiang. / Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma. In: Pain. 2015 ; Vol. 156, No. 4. pp. 711-721.
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