Profound alteration in cutaneous primary afferent activity produced by inflammatory mediators
- University of Wyoming, United States
- University of Alabama at Birmingham, United States
- University of Pittsburgh, United States
Abstract
Inflammatory pain is thought to arise from increased transmission from nociceptors and recruitment of 'silent' afferents. To evaluate inflammation-induced changes, mice expressing GCaMP3 in cutaneous sensory neurons were generated and neuronal responses to mechanical stimulation in vivo before and after subcutaneous infusion of an 'inflammatory soup' (IS) were imaged in an unanesthetized preparation. Infusion of IS rapidly altered mechanical responsiveness in the majority of neurons. Surprisingly, more cells lost, rather than gained, sensitivity and 'silent' afferents that were mechanically insensitive and gained mechanosensitivity after IS exposure were rare. However, the number of formerly silent afferents that became mechanosensitive was increased 5-fold when the skin was heated briefly prior to infusion of IS. These findings suggest that pain arising from inflamed skin reflects a dramatic shift in the balance of sensory input, where gains and losses in neuronal populations results in novel output that is ultimately interpreted by the CNS as pain.
Article and author information
Author details
Funding
National Institutes of Health (NS31826)
- Brian M Davis
National Institutes of Health (DK101681)
- Jennifer J DeBerry
National Institutes of Health (NS044094)
- Jeffery C Woodbury
National Institutes of Health (RR032128)
- Jeffery C Woodbury
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All studies were performed in accordance within guidelines of the Institutional Animal Care and Use Committees at the Universities of Pittsburgh and Wyoming and the National Institutes of Health guidelines for the Care and Use of Laboratory Animals. Approved animal protocol numbers include Univ. of Wyoming IACUC protocol #20131206JW00049-03 (for in vivo studies), # p20131203JW00048-3-03 (for ex vivo studies) and University of Pittsburgh IACUC protocol # 15106942 (for calcium imaging studies).
Copyright
© 2016, Smith-Edwards et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Profound alteration in cutaneous primary afferent activity produced by inflammatory mediators
eLife 5:e20527.
https://doi.org/10.7554/eLife.20527
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