Astroglial MicroRNA-219-5p in the Ventral Tegmental Area Regulates Nociception in Rats

作者：Zhang, Song; Yang, Xiao-Na; Zang, Ting; Luo, Jun; Pan, Zhiqiang; Wang, Lei; Liu, He; Liu, Di; Li, Yan-Qiang; Zhang, Yao-Dong; Zhang, Hongxing; Ding, Hai-Lei; Cao, Jun-Li^*

来源：Anesthesiology, 2017, 127(3): 548-564.

DOI：10.1097/ALN.0000000000001720

• NEUROPATHIC PAIN
• CENTRAL SENSITIZATION
• ASTROCYTE ACTIVATION
• DOPAMINE NEURONS
• REWARD CIRCUITRY
• MECHANICAL ALLODYNIA
• NUCLEUS-ACCUMBENS
• DORSAL-HORN
• SPINAL-CORD
• EXPRESSION

Background: The authors previously reported that noncoding microRNA miR-219-5p is down-regulated in the spinal cord in a nociceptive state. The ventral tegmental area also plays critical roles in modulating nociception, although the underlying mechanism remains unknown. The authors hypothesized that miR-219-5p in the ventral tegmental area also may modulate nociception.
Methods: The authors studied the bidirectional regulatory role of ventral tegmental area miR-219-5p in a rat complete Freund's adjuvant model of inflammatory nociception by measuring paw withdrawal latencies. Using molecular biology technologies, the authors measured the effects of astroglial coiled-coil and C2 domain containing 1A/nuclear factor kappa B cascade and dopamine neuron activity on the down-regulation of ventral tegmental area miR-219-5p-induced nociceptive responses.
Results: MiR-219-5p expression in the ventral tegmental area was reduced in rats with thermal hyperalgesia. Viral overexpression of ventral tegmental area miR-219-5p attenuated complete Freund's adjuvant-induced nociception from 7 days after complete Freund's adjuvant injection (paw withdrawal latencies: 6.09 +/- 0.83 s vs. 3.96 +/- 0.76 s; n = 6/group). Down-regulation of ventral tegmental area miR-219-5p in naive rats was sufficient to induce thermal hyperalgesia from 7 days after lentivirus injection (paw withdrawal latencies: 7.09 +/- 1.54 s vs. 11.75 +/- 2.15 s; n = 8/group), which was accompanied by increased glial fibrillary acidic protein (fold change: 2.81 +/- 0.38; n = 3/group) and reversed by intraventral tegmental area injection of the astroglial inhibitor fluorocitrate. The nociceptive responses induced by astroglial miR-219-5p down-regulation were inhibited by interfering with astroglial coiled-coil and C2 domain containing 1A/nuclear factor-kappa B signaling. Finally, pharmacologic inhibition of ventral tegmental area dopamine neurons alleviated this hyperalgesia.
Conclusions: Down-regulation of astroglial miR-219-5p in ventral tegmental area induced nociceptive responses are mediated by astroglial coiled-coil and C2 domain containing 1A/nuclear factor-kappa B signaling and elevated dopamine neuron activity.

• 出版日期2017-9
• 单位徐州医科大学