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TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons.

ABSTRACT: The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses to both innocuous and noxious mechanical force. Mechanically evoked action potentials in cutaneous myelinated A-fiber and unmyelinated C-fiber neurons were quantified using the ex vivo skin-nerve preparation to record from the saphenous nerve, which terminates in the dorsal hairy skin of the hindpaw. Our data reveal that in TRPC1-deficient mice, mechanically evoked action potentials were decreased by nearly 50% in slowly adapting A?-fibers, which largely innervate Merkel cells, and in rapidly adapting A?-Down-hair afferent fibers compared with wild-type controls. In contrast, differences were not found in slowly adapting A?-mechanoreceptors or unmyelinated C-fibers, which primarily respond to nociceptive stimuli. These results suggest that TRPC1 may be important in the detection of innocuous mechanical force. We concurrently investigated the role of TRPC1 in behavioral responses to mechanical force to the plantar hindpaw skin. For innocuous stimuli, we developed a novel light stroke assay using a "puffed out" cotton swab. Additionally, we used repeated light, presumably innocuous punctate stimuli with a low threshold von Frey filament (0.68 mN). In agreement with our electrophysiological data in light-touch afferents, TRPC1-deficient mice exhibited nearly a 50% decrease in behavioral responses to both the light-stroke and light punctate mechanical assays when compared with wild-type controls. In contrast, TRPC1-deficient mice exhibited normal paw withdrawal response to more intense mechanical stimuli that are typically considered measures of nociceptive behavior.

SUBMITTER: Garrison SR

PROVIDER: S-EPMC3289471 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons.

Garrison Sheldon R SR Dietrich Alexander A Stucky Cheryl L CL

Journal of neurophysiology 20111109 3

The cellular proteins that underlie mechanosensation remain largely enigmatic in mammalian systems. Mechanically sensitive ion channels are thought to distinguish pressure, stretch, and other types of tactile signals in skin. Transient receptor potential canonical 1 (TRPC1) is a candidate mechanically sensitive channel that is expressed in primary afferent sensory neurons. However, its role in the mechanical sensitivity of these neurons is unclear. Here, we investigated TRPC1-dependent responses ...[more]

PMID: 22072513

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Project description:Background and purposeStroke rehabilitation does not often integrate both sensory and motor recovery. While subthreshold noise was shown to enhance sensory signal detection at the site of noise application, having a noise-generating device at the fingertip to enhance fingertip sensation and potentially enhance dexterity for stroke survivors is impractical, since the device would interfere with object manipulation. This study determined if remote application of subthreshold vibrotactile noise (away from the fingertips) improves fingertip tactile sensation with potential to enhance dexterity for stroke survivors.MethodsIndex finger and thumb pad sensation was measured for ten stroke survivors with fingertip sensory deficit using the Semmes-Weinstein Monofilament and Two-Point Discrimination Tests. Sensation scores were measured with noise applied at one of three intensities (40%, 60%, 80% of the sensory threshold) to one of four locations of the paretic upper extremity (dorsal hand proximal to the index finger knuckle, dorsal hand proximal to the thumb knuckle, dorsal wrist, volar wrist) in a random order, as well as without noise at beginning (Pre) and end (Post) of the testing session.ResultsVibrotactile noise of all intensities and locations instantaneously and significantly improved Monofilament scores of the index fingertip and thumb tip (p < .01). No significant effect of the noise was seen for the Two-Point Discrimination Test scores.ConclusionsRemote application of subthreshold (imperceptible) vibrotactile noise at the wrist and dorsal hand instantaneously improved stroke survivors' light touch sensation, independent of noise location and intensity. Vibrotactile noise at the wrist and dorsal hand may have enhanced the fingertips' light touch sensation via stochastic resonance and interneuronal connections. While long-term benefits of noise in stroke patients warrants further investigation, this result demonstrates potential that a wearable device applying vibrotactile noise at the wrist could enhance sensation and grip ability without interfering with object manipulation in everyday tasks.

Project description:BackgroundAcupuncture has been shown to reduce pain, and acupuncture-induced sensation may be important for this analgesia. In addition, cognitive coping strategies can influence sensory perception. However, the role of coping strategy on acupuncture modulation of pain and sensory thresholds, and the association between acupuncture sensation and these modulatory effects, is currently unknown.MethodsElectroacupuncture (EA) was applied at acupoints ST36 and GB39 of 61 healthy adults. Different coping conditions were experimentally designed to form an active coping strategy group (AC group), who thought they could control EA stimulation intensity, and a passive coping strategy group (PC group), who did not think they had such control. Importantly, neither group was actually able to control EA stimulus intensity. Quantitative sensory testing was performed before and after EA, and consisted of vibration (VDT), mechanical (MDT), warm (WDT), and cold (CDT) detection thresholds, and pressure (PPT), mechanical (MPT), heat (HPT) and cold (CPT) pain thresholds. Autonomic measures (e.g. skin conductance response, SCR) were also acquired to quantify physiological response to EA under different coping conditions. Subjects also reported the intensity of any acupuncture-induced sensations.ResultsCoping strategy was induced with successful blinding in 58% of AC subjects. Compared to PC, AC showed greater SCR to EA. Under AC, EA reduced PPT and CPT. In the AC group, improved pain and sensory thresholds were correlated with acupuncture sensation (VDTchange vs. MI: r=0.58, CDTchange vs. tingling: r=0.53, CPTchange vs. tingling; r=0.55, CPTchange vs. dull; r=0.55). However, in the PC group, improved sensory thresholds were negatively correlated with acupuncture sensation (CDTchange vs. intensity sensitization: r=-0.52, WDTchange vs. fullness: r=-0.57).ConclusionsOur novel approach was able to successfully induce AC and PC strategies to EA stimulation. The interaction between psychological coping strategy and acupuncture sensation intensity can differentially modulate pain and sensory detection threshold response to EA. In a clinical context, our findings suggest that instructions given to the patient can significantly affect therapeutic outcomes and the relationship between acupuncture intensity and clinical response. Specifically, acupuncture analgesia can be enhanced by matching physical stimulation intensity with psychological coping strategy to acupuncture contexts.Trial registrationKCT0000905.

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TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons.

Publications

TRPC1 contributes to light-touch sensation and mechanical responses in low-threshold cutaneous sensory neurons.

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