Effects of inflammation on the properties of Nav1.8ChR2-positive and Nav1.8ChR2-negative afferent mechanoreceptors in the hindpaw glabrous skin of mice.

We recently used Nav1.8ChR2 mice in which Nav1.8-expressing afferents were optogenetically tagged to classify mechanosensitive afferents into Nav1.8ChR2-postive and Nav1.8ChR2-negative mechanoreceptors. We found that the former were mainly high threshold mechanoreceptors (HTMRs), while the latter were low threshold mechanoreceptors (LTMRs). In the present study, we further investigated whether the properties of these mechanoreceptors were altered following tissue inflammation. Nav1.8ChR2 mice received a subcutaneous injection of saline or Complete Freund's Adjuvant (CFA) in the hindpaws. Using the hindpaw glabrous skin-tibial nerve preparation and the pressure-clamped single-fiber recordings, we found that CFA-induced hindpaw inflammation lowered the mechanical threshold of many Nav1.8ChR2-postive Aβ-fiber mechanoreceptors but heightened the mechanical threshold of many Nav1.8ChR2-negative Aβ-fiber mechanoreceptors. Spontaneous action potential impulses were not observed in Nav1.8ChR2-postive Aβ-fiber mechanoreceptors, but occurred in Nav1.8ChR2-negative Aβ-fiber mechanoreceptors with a lower mechanical threshold in the saline group and a higher mechanical threshold in the CFA group. No significant change was observed in the mechanical sensitivity of Nav1.8ChR2-postive and Nav1.8ChR2-negative Aδ-fiber mechanoreceptors as well as Nav1.8ChR2-postive C-fiber mechanoreceptors following hindpaw inflammation. Collectively, inflammation significantly altered the functional properties of both Nav1.8ChR2-postive and Nav1.8ChR2-negative Aβ-fiber mechanoreceptors, which may contribute to mechanical allodynia during inflammation.