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.
BACKGROUND
A 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.


RESULTS
We 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).


CONCLUSIONS
These 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.
School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia. S.Nagi@uws.edu.au.
Saad S
SS
Nagi
School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia. James.Dunn@uws.edu.au.
James S
JS
Dunn
Neuroscience Research Australia, PO Box 1165, Randwick, NSW, 2031, Australia. I.Birznieks@unsw.edu.au.|School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia. I.Birznieks@unsw.edu.au.
Ingvars
I
Birznieks
School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia. Richard.Vickery@unsw.edu.au.
Richard M
RM
Vickery
School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW, 2751, Australia. D.Mahns@uws.edu.au.
David A
DA
Mahns
D000293:Adolescent; D000328:Adult; D044482:Benzeneacetamides / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D005260:Female; D006225:Hand / Q000294:innervation; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects* / Q000378:metabolism; D009407:Nerve Block; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D011725:Pyridines / Q000494:pharmacology*; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000187:drug effects / Q000294:innervation; D055698:Touch Perception / Q000187:drug effects / Q000502:physiology; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology*; D055815:Young Adult
C553486:2-(4-cyclopropylphenyl)-N-(1-(5-((2,2,2-trifluoroethyl)oxo)pyridin-2-yl)ethyl)acetamide; D044482:Benzeneacetamides; C479952:CACNA1H protein, human; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D011725:Pyridines; D061567:Voltage-Gated Sodium Channel Blockers; D008012:Lidocaine