Electrophysiological and Behavioral Evaluation of C-LTMR Plasticity Induced by Spinal Cord Injury: Transformation from Pleasure to Pain Afferents
Technical Report,30 Sep 2015,29 Sep 2018
Emory University School of Medicine Atlanta United States
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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 iSCI modifies C-LTMRs recruitment and activation properties,iiC-LTMR plasticity after SCI contributes to at-level mechanical allodynia andiiisympathetic 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-stimulatedescape 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 andor 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.
- Anatomy and Physiology
- Medicine and Medical Research