Pain Medicine  |   September 2017
Astroglial MicroRNA-219-5p in the Ventral Tegmental Area Regulates Nociception in Rats
Author Notes
  • From Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University (S.Z., X.-N.Y., T.Z., J.L., Z.P., L.W., H.L., D.L., Y.-Q.L., Y.-D.Z., H.Z., H.-L.D., J.-L.C.) and Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University (H.L., J.-L.C.), Xuzhou, China.
  • S.Z., X.-N.Y., and T.Z. contributed equally to this article.
    S.Z., X.-N.Y., and T.Z. contributed equally to this article.×
  • Submitted for publication October 26, 2016. Accepted for publication May 5, 2017.
    Submitted for publication October 26, 2016. Accepted for publication May 5, 2017.×
  • Address correspondence to Dr. Cao: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China, or Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China. caojl0310@aliyun.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Pain Medicine / Basic Science / Central and Peripheral Nervous Systems / Pain Medicine / Pharmacology
Pain Medicine   |   September 2017
Astroglial MicroRNA-219-5p in the Ventral Tegmental Area Regulates Nociception in Rats
Anesthesiology 9 2017, Vol.127, 548-564. doi:10.1097/ALN.0000000000001720
Anesthesiology 9 2017, Vol.127, 548-564. doi:10.1097/ALN.0000000000001720
Abstract

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 κB 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 naïve 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-κB 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-κB signaling and elevated dopamine neuron activity.