Electrophysiological and Behavioral Evaluation of C-LTMR Plasticity Induced by Spinal Cord Injury: Transformation from Pleasure to Pain Afferents
Abstract
C-low threshold mechanoreceptors (C-LTMRs) are a sub-population of cutaneous afferents that innervate hairy skin and encode pleasant touch. The study tests the hypothesis that C-LTMRs are transformed into allodynia-encoding nociceptors after spinal cord injury (SCI). In rodents, C-LTMRs can be selectively identified by their expression of tyrosine hydroxylase (TH). Using transgenic TH-Cre mice, we proposed to examine whether (i)SCI modifies C-LTMRs recruitment and activation properties,(ii)C-LTMR plasticity after SCI contributes to at-level mechanical allodynia and(iii)sympathetic activity modulates C-LTMR activity and the expression of neuropathic pain. Overall, we acquired data that align with or fully support the general hypothesis. First, we report that using a tamoxifen-inducible strain of TH-Cre mice, neural responses are evoked by selective activation of TH+ C-LTMRs in the sciatic nerve and trunk skin. Second, we show that SCI and mechanical truncal stimulation (only after SCI) induce short-lasting increases in respiratory rates (RRs) in adult mice. Third, using two place preference behavioral paradigms, TH-Cre mice with a SCI show a significant increase in time spent in the non-stimulated(escape chamber) immediately after mechanical or optical stimulation of the trunk. This effect developed at 3 weeks and persisted to at least 5 weeks after SCI. Interestingly, SCI mice also showed significant hind-paw hypersensitivity compared to pre-stimulation and/or sham and nave control mice. Overall, these observations suggest that mechanical truncal stimulation, that is consistent with C-LTMRs recruitment, elicits an aversive (not pleasurable) response after SCI, which strongly supports our hypothesis. Moreover, the findings suggest that C-LTMRs may indeed signal pain after SCI.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2018
- Accession Number
- AD1095409
Entities
People
- Sandra M Garraway
- Shawn Hochman
Organizations
- Emory University School of Medicine