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.
- Brian M Davis
- Jennifer J DeBerry
- Jeffery C Woodbury
- Jeffery C Woodbury
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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).
- David D Ginty, Howard Hughes Medical Institute, Harvard Medical School, United States
© 2016, Smith-Edwards et al.
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