Abstract
IntroductionThe sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear.MethodsC‐nociceptors from two patients with late onset of erythromelalgia‐like pain, signs of small fiber neuropathy, and rare genetic variants of Nav 1.9 (N1169S, I1293V) were assessed by microneurography.ResultsCompared with patients with comparable pain phenotypes (erythromelalgia‐like pain without Nav‐mutations and painful polyneuropathy), there was a tendency toward more activity‐dependent slowing of conduction velocity in mechanoinsensitive C‐nociceptors. Hyperexcitability to heating and electrical stimulation were seen in some nociceptors, and other unspecific signs of increased excitability, including spontaneous activity and mechanical sensitization, were also observed.ConclusionsAlthough the functional roles of these genetic variants are still unknown, the microneurography findings may be compatible with increased C‐nociceptor excitability based on increased Nav 1.9 function.
Highlights
The sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear
The two adult female patients underwent assessment of thermal detection thresholds (as described elsewhere (Warncke, Jorum, & Stubhaug, 1997), electromyography/neurography as well as microneurography recordings from individual cutaneous C-fibers in the peroneal nerve (Kleggetveit et al, 2012; Orstavik et al, 2003; Schmelz et al, 1995). Based on their sensory and axonal characteristics assessed by microneurography, C-nociceptors were further subclassified as either mechanosensitive (CM-) or mechanoinsensitive (CMi-) nociceptors
We add data from a later third recording session and present an extended analysis of the data, given the information that patient 1 was identified with a rare genetic variant of Nav 1.9 (Zhang et al, 2014)
Summary
The sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear. Methods: C-n ociceptors from two patients with late onset of erythromelalgia-like pain, signs of small fiber neuropathy, and rare genetic variants of Nav 1.9 (N1169S, I1293V) were assessed by microneurography. Results: Compared with patients with comparable pain phenotypes (erythromelalgia- like pain without Nav-mutations and painful polyneuropathy), there was a tendency toward more activity-dependent slowing of conduction velocity in mechanoinsensitive C-nociceptors. Hyperexcitability to heating and electrical stimulation were seen in some nociceptors, and other unspecific signs of increased excitability, including spontaneous activity and mechanical sensitization, were observed. Conclusions: the functional roles of these genetic variants are still unknown, the microneurography findings may be compatible with increased C-nociceptor excitability based on increased Nav 1.9 function. KEYWORDS microneurography, nociceptors, pain 1 | INTRODUCTION
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