SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model

Background The transcriptional repressor positive regulatory domain I–binding factor 1 (PRDM1) is expressed in adult mouse dorsal root ganglion and regulates the formation and function of peripheral sensory neurons. The authors hypothesized that PRDM1 in the dorsal root ganglion may contribute to peripheral nerve injury–induced nociception regulation and that its mechanism may involve Kv4.3 channel transcriptional repression. Methods Nociception was induced in C57BL/6 mice by applying chronic constriction injury, complete Freund’s adjuvant, or capsaicin plantar injection. Nociceptive response was evaluated by mechanical allodynia, thermal hyperalgesia, cold hyperalgesia, or gait analysis. The role of PRDM1 was evaluated by injection of Prdm1 knockdown and overexpression adeno-associated viruses. The interaction of PRDM1 at the Kv4.3 (Kcnd3) promoter was evaluated by chromatin immunoprecipitation assay. Excitability of dorsal root ganglion neurons was evaluated by whole cell patch clamp recordings, and calcium signaling in spinal dorsal horn neurons was evaluated by in vivo two-photon imaging. Results Peripheral nerve injury increased PRDM1 expression in the dorsal root ganglion, which reduced the activity of the Kv4.3 promoter and repressed Kv4.3 channel expression (injured vs. uninjured; all P < 0.001). Knockdown of PRDM1 rescued Kv4.3 expression, reduced the high excitability of injured dorsal root ganglion neurons, and alleviated peripheral nerve injury–induced nociception (short hairpin RNA vs. Scram; all P < 0.05). In contrast, PRDM1 overexpression in naive mouse dorsal root ganglion neurons diminished Kv4.3 channel expression and induced hyperalgesia (PRDM1 overexpression vs. control, mean ± SD; n = 13; all P < 0.0001) as evaluated by mechanical allodynia (0.6 ± 0.3 vs. 1.2 ± 0.2 g), thermal hyperalgesia (5.2 ± 1.3 vs. 9.8 ± 1.7 s), and cold hyperalgesia (3.4 ± 0.5 vs. 5.3 ± 0.6 s). Finally, PRDM1 downregulation in naive mice reduced the calcium signaling response of spinal dorsal horn neurons to thermal stimulation. Conclusions PRDM1 contributes to peripheral nerve injury–induced nociception by repressing Kv4.3 channel expression in injured dorsal root ganglion neurons. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Download Full-text

Inflammatory pain mediated by a phenotypic switch in brain-derived neurotrophic factor-immunoreactive dorsal root ganglion neurons innervating the lumbar facet joints in rats

Neuroscience Letters ◽

10.1016/s0304-3940(02)00120-9 ◽

2002 ◽

Vol 323 (2) ◽

pp. 129-132 ◽

Cited By ~ 17

Author(s):

Seiji Ohtori ◽

Kazuhisa Takahashi ◽

Hideshige Moriya

Keyword(s):

Dorsal Root Ganglion ◽

Neurotrophic Factor ◽

Inflammatory Pain ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Facet Joints ◽

Phenotypic Switch ◽

Ganglion Neurons ◽

Lumbar Facet ◽

Lumbar Facet Joints

Download Full-text

Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats

European Spine Journal ◽

10.1007/s00586-013-2733-5 ◽

2013 ◽

Vol 22 (8) ◽

pp. 1794-1799 ◽

Cited By ~ 7

Author(s):

Yusuke Matsuura ◽

Seiji Ohtori ◽

Nahoko Iwakura ◽

Takane Suzuki ◽

Kazuki Kuniyoshi ◽

...

Keyword(s):

Transcription Factor ◽

Dorsal Root Ganglion ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Activating Transcription Factor 3 ◽

Pain Model ◽

Lower Trunk ◽

Activating Transcription Factor ◽

Ganglion Neurons ◽

Transcription Factor 3

Download Full-text

Nogo-A Induced Polymerization of Microtubule Is Involved in the Inflammatory Heat Hyperalgesia in Rat Dorsal Root Ganglion Neurons

International Journal of Molecular Sciences ◽

10.3390/ijms221910360 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10360

Author(s):

Ling Chen ◽

Qiguo Hu ◽

Huaicun Liu ◽

Yan Zhao ◽

Sun-On Chan ◽

...

Keyword(s):

Dorsal Root Ganglion ◽

Inflammatory Pain ◽

Dorsal Root ◽

Intrathecal Injection ◽

Dorsal Root Ganglion Neurons ◽

Microtubule Assembly ◽

Major Constituent ◽

Drg Neurons ◽

Ganglion Neurons ◽

Heat Hyperalgesia

The microtubule, a major constituent of cytoskeletons, was shown to bind and interact with transient receptor potential vanilloid subfamily member 1 (TRPV1), and serves a pivotal role to produce thermal hyperalgesia in inflammatory pain. Nogo-A is a modulator of microtubule assembly and plays a key role in maintaining the function of TRPV1 in inflammatory heat pain. However, whether the microtubule dynamics modulated by Nogo-A in dorsal root ganglion (DRG) neurons participate in the inflammatory pain is not elucidated. Here we reported that the polymerization of microtubules in the DRG neurons, as indicated by the acetylated α-tubulin, tubulin polymerization-promoting protein 3 (TPPP3), and microtubule numbers, was significantly elevated in the complete Freund’s adjuvant (CFA) induced inflammatory pain. Consistent with our previous results, knock-out (KO) of Nogo-A protein significantly attenuated the heat hyperalgesia 72 h after CFA injection and decreased the microtubule polymerization via up-regulation of phosphorylation of collapsin response mediator protein 2 (CRMP2) in DRG. The colocalization of acetylated α-tubulin and TRPV1 in DRG neurons was also reduced dramatically in Nogo-A KO rats under inflammatory pain. Moreover, the down-regulation of TRPV1 in DRG of Nogo-A KO rats after injection of CFA was reversed by intrathecal injection of paclitaxel, a microtubule stabilizer. Furthermore, intrathecal injection of nocodazole (a microtubule disruptor) attenuated significantly the CFA-induced inflammatory heat hyperalgesia and the mechanical pain in a rat model of spared nerve injury (SNI). In these SNI cases, the Nogo-A and acetylated α-tubulin in DRG were also significantly up-regulated. We conclude that the polymerization of microtubules promoted by Nogo-A in DRG contributes to the development of inflammatory heat hyperalgesia mediated by TRPV1.

Download Full-text