The effects of preferential A- and C-fibre blocks and T-type calcium channel antagonist on detection of low-force monofilaments in healthy human participants.

Saad S Nagi,David A Mahns,Ingvars Birznieks,James S Dunn,Richard M Vickery

doi:10.1186/s12868-015-0190-2

Saad S Nagi, David A Mahns + Show 3 more

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https://doi.org/10.1186/s12868-015-0190-2

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Abstract

BackgroundA myriad of studies have argued that tactile sensibility is underpinned exclusively by large myelinated mechanoreceptors. However, the functional significance of their slow-conducting counterparts, termed C-low threshold mechanoreceptors (C-LTMRs), remains largely unexplored. We recently showed the emergence of brush- and vibration-evoked allodynia in human hairy and glabrous skin during background muscle pain. The allodynia persisted following the preferential blockade of myelinated fibres but was abolished by the preferential blockade of cutaneous C fibres, thereby suggesting a pathway involving hairy skin C-LTMRs and their functional counterparts in glabrous skin in this phenomenon. In the present study, we tested the effects of preferential A- and C-fibre conduction blocks and pharmacological blockade of T-type calcium channel Cav3.2 (expressed selectively on small-fibre LTMRs) on monofilament detection thresholds in healthy participants by compression, low-dose intradermal anaesthesia (xylocaine 0.25 %) and selective T-channel antagonist, TTA-A2.ResultsWe found that all participants could detect monofilament contacts (as low as 1.6 mN) within the innocuous tactile range regardless of the preferential blockade of myelinated fibres. Furthermore, during the compression block no subject reported a switch in modality from touch to pain. That is, the low-force monofilament contacts were always perceived as non-painful. However, there was a small but significant elevation of monofilament thresholds (~2 mN) in the glabrous skin following the compression block. Importantly, no differences were found in the thresholds across hairy and glabrous regions while the myelinated fibres were conducting or not. The preferential blockade of C fibres in the glabrous skin (with myelinated fibres intact) also resulted in a small but significant elevation of tactile thresholds. Furthermore, the use of T-channel blocker in the glabrous skin during compression block of myelinated fibres resulted in complete abolition of monofilament sensibility within the innocuous tactile range (tested up to ~20 mN).ConclusionsThese observations suggest that C-LTMRs need not be regarded as a redundant tactile system, but appear to complement normal large-myelinated-fibre tactile function. Convergent findings in glabrous and hairy skin lend support for an underlying system of innocuous mechanoreception with Cav3.2-expressing unmyelinated fibres.

Highlights

A myriad of studies have argued that tactile sensibility is underpinned exclusively by large myelinated mechanoreceptors
We recently provided psychophysical evidence for the existence of an apparent ‘functional homologue’ of C-low threshold mechanoreceptors (C-LTMRs) in human glabrous skin based on: (1) the production of cutaneous allodynia during background muscle pain by applying focal vibratory stimuli and gentle brushing to glabrous skin at stroking speeds deemed optimal for C-LTMR activation in hairy skin; (2) the persistence of allodynia following the preferential blockade of myelinated fibres by compression; (3) the abolition of allodynia following the preferential blockade of C fibres by injecting a small amount of low-dose anaesthetic into the glabrous skin [16]
Localised blockade of T‐type calcium (Cav3.2) channels in the compression condition We examined whether the C-fibre contribution from glabrous skin is dependent on the Cav3.2 calcium channels by injecting 0.5 ml of 1 mg/ml TTA-A2—a selective T-type calcium channel antagonist—into the distal palmar pad of little finger in 5 participants. 5-mg TTA-A2 powder was dissolved in 0.5-ml alcohol and 0.1-ml aliquots were diluted in 0.9-ml normal saline to produce a 1 mg/ml solution

Summary

Introduction

A myriad of studies have argued that tactile sensibility is underpinned exclusively by large myelinated mechanoreceptors. The functional significance of their slow-conducting counterparts, termed C-low threshold mechanoreceptors (C-LTMRs), remains largely unexplored. The allodynia persisted following the preferential blockade of myelinated fibres but was abolished by the preferential blockade of cutaneous C fibres, thereby suggesting a pathway involving hairy skin C-LTMRs and their functional counterparts in glabrous skin in this phenomenon. It is widely appreciated that large myelinated mechanoreceptors are the underlying neural substrate of sensorydiscriminative touch, which includes the perception of pressure, vibration/texture, skin stretch, and in case of hairy skin, displacement of hair follicles [1,2,3,4]. Based on a phylogenetic classification, C mechanoreceptors represent a very ancient system of slowly conducting unmyelinated afferents. This afferent class was first reported by Zotterman [5] in the hairy skin of cat. Despite initial failure to discover this afferent class in humans, subsequent microneurography studies have confirmed their ubiquitous distribution in human hairy skin [11,12,13,14,15]

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