Volume 10 Supplement 1

Proceedings of the Seventh Scientific Meeting of The TMJ Association

Open Access

Imaging orofacial pain in mice

  • Yu Shin Kim1,
  • Yuxia Chu2,
  • Liang Han1,
  • Kyougsook Park1, 5,
  • Man Li2, 3,
  • Zhe Li1,
  • Pamela Colleen LaVinka1,
  • Michael J Caterina1, 4,
  • Ke Ren2,
  • Ronald Dubner2,
  • Feng Wei2 and
  • Xinzhong Dong1, 5
Molecular Pain201410(Suppl 1):O2

https://doi.org/10.1186/1744-8069-10-S1-O2

Published: 15 December 2014

Nociceptors in the dorsal root ganglia (DRG) and trigeminal ganglion (TG) play an essential role in initiating pain by detecting painful stimuli through their peripheral axons and sending signals to the spinal cord via their central axons [1]. Pathological conditions such as inflammation and nerve injury can sensitize nociceptors, causing heightened pain sensitivity and often leading to chronic pain conditions like TMJ disorders. Despite its importance in understanding the mechanism of nociceptor sensitization, monitoring neuronal activity of nociceptors in tissue explants or in live animals is still technically challenging due to the interference of the surrounding tissues. Recently, we have developed a novel approach to directly monitor neuronal activity and hyperactivity after injury and revealed the contribution of central terminal sensitization of primary nociceptive neurons to molecular mechanisms underlying the maintenance of trigeminal neuropathic pain. We generated Pirt-GCaMP3 mice in which GCaMP3, a genetic-encoded Ca2+-sensitive indicator [2], is specifically expressed in >95% of all DRG and TG neurons under the Pirt promoter[3]. Because of the specific expression of the Ca2+ sensor (i.e., only in DRG and TG and not in skin cells or spinal cord neurons), we detected robust neuronal hyperexcitability in TG explants and TG’s axons in the skin explants and trigeminal brain-stem slices of animals with nerve injury compared with naïve or sham-treated mice. In addition, we are developing techniques to image DRG neuronal activity in live mice in response to various sensory stimuli applied to sensory peripheral receptive fields. The advantages of the functional imaging using Pirt-GCaMP3 mice include simple tissue preparation and imaging procedures, intact sensory somatotopic organization, and simultaneously monitoring a large population of neurons and nerves. Previous and ongoing studies using this technique have revealed new mechanisms underlying chronic pain conditions including orofacial pain.

Disclosures

Dr. Caterina is an inventor on a patent on the use of products related to TRPV1, which is licensed through UCSF and Merck, and may be entitled to royalties related to these products. He is on the Scientific Advisory Board for Hydra Biosciences, which develops products related to TRP channels. These conflicts are being managed by the Johns Hopkins Office on Policy Coordination.

Declarations

Acknowledgements

We thank Dr. Loren Looger at Howard Hughes Medical Institute, Janelia Farm for providing us GCaMP3 cDNA and Yixun Geng for technical assistance. We thank Chip Hawkins and Holly Wellington of Transgenic Mouse Core at Johns Hopkins University School of Medicine for assistance with Pirt-GCaMP3 mouse generation. This work was supported by National Institutes of Health Grants (R01DE022750 and R01GM087369 to X.D.; R01DE018573 to F.W.), Johns Hopkins University Brain Science Institute grant, and T32 (T32NS070201 to Y.S.K.) Johns Hopkins University Pain Fellowship.

Authors’ Affiliations

(1)
Department of Neuroscience, Center of Sensory Biology, The Johns Hopkins University School of Medicine
(2)
Department of Neural and Pain Sciences, Program in Neuroscience, Dental School, University of Maryland
(3)
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
(4)
Department of Biological Chemistry, The Johns Hopkins University School of Medicine
(5)
Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine

References

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Copyright

© Kim et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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