Sensory receptors in mammalian skin in an in vitro preparation

doi:10.1016/0304-3940(86)90180-1

Neuroscience Letters

Volume 66, Issue 2, 15 May 1986, Pages 141-146

https://doi.org/10.1016/0304-3940(86)90180-1 Get rights and content

Abstract

The saphenous nerve and a patch of innervated skin were excised from the rat and guinea pig and kept in modified Krebs-Henseleit solution. The nerve was split into filaments and single fibre action potentials were recorded. Various cutaneous receptors could be identified by adequate stimulation of the superfused skin with radiant heat, von Frey hairs, constant pressure, cold and chemical stimuli restricted to receptive fields. In comparison to previous in vivo experiments no obvious differences occurred with respect to excitability and spontaneous activity. Within 12 h after excision of the skin no time-related changes in receptor behaviour became obvious.

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Cited by (233)

Multisite silicon probes enable simultaneous recording of spontaneous and evoked activity in multiple isolated C-fibres in rat saphenous nerve
2022, Journal of Neuroscience Methods
Recordings of electrical activity in nerves have provided valuable insights into normal function and pathological behaviours of the nervous system. Current high-resolution techniques (e.g. teased fibre recordings) typically utilise electrodes with a single recording site, capturing the activity of a single isolated neuron per recording.
We conducted proof-of-principle C-fibre recordings in the saphenous nerve of urethane-anaesthetised adult Wistar rats using 32-channel multisite silicon electrodes. Data was acquired using the OpenEphys recording system and clustered offline with Kilosort 2.5.
In single recordings in 5 rats, 32 units with conduction velocities in the C-fibre range (< 1 m/s) were identified via constant latency responses and classified using activity dependent slowing. In two animals, 6 C-fibres (5 classified as nociceptors) were well isolated after clustering. Their activity could be tracked throughout the recording – including during periods of spontaneous activity. Axonal conduction velocities were calculated from spontaneous activity and/or low frequency electrical stimulation using only the differences in action potential latency as it propagated past multiple probe sites.
Single electrode approaches have a low data yield and generating group data for specific fibre types is challenging as it requires multiple experimental subjects and recording sessions. This is particularly true when the experimental targets are the small, unmyelinated C-fibres carrying nociceptive information.
We demonstrate that multisite recordings can greatly increase experimental yields and enhance fibre identification. The approach is of particular utility when coupled with clustering analysis. Multisite probes and analysis approaches constitute a valuable new toolbox for researchers studying the peripheral nervous system.
SGK1.1 isoform is involved in nociceptive modulation, offering a protective effect against noxious cold stimulus in a sexually dimorphic manner
2022, Pharmacology Biochemistry and Behavior
The serum and glucocorticoid-regulated kinase 1 (SGK1) is a widely expressed protein in the Central Nervous System (CNS), involved in regulating the activity of a wide variety of ion channels and transporters and physiological functions, such as neuronal excitability. SGK1.1 is a neuronal splice isoform of SGK1, expressed exclusively in the CNS, distributed in brain and cerebellum, that decreases neuronal excitability via up-regulation of M-current, linked to Kv7.2/3 potassium channels. Strategies to maintain increased SGK1.1 activity could be helpful in decreasing neuronal hyperexcitability, as occurs in neuropathic pain. Transgenic mice overexpressing SGK1.1 (B6.Tg.sgk1) offer a particularly relevant opportunity to assess the physiological involvement of this protein in nociception.
Behavior and physiological nociception were evaluated in male and female B6.Tg.sgk1 and wild-type mice (B6.WT), characterizing nociceptive thresholds to different nociceptive stimuli (thermal, chemical and mechanical), as well as the electrophysiological properties of cutaneous sensory Aδ-fibres isolated from the saphenous nerve. The acute antinociceptive effect of morphine was also evaluated.
Compared with B6.WT animals, male and female B6.Tg.sgk1 mice showed increased spontaneous locomotor activity. Regarding nociception, there were no differences between transgenic and wild-type mice in heat, chemical and mechanical thresholds, but interestingly, male B6.Tg.sgk1 mice were less sensitive to cold stimulus; B6.Tg.sgk1 animals showed lower sensitivity to morphine. Electrophysiological properties of cutaneous primary afferent fibres were maintained.
This is the first demonstration that the SGK1.1 isoform is involved in nociceptive modulation, offering a protective effect against noxious cold stimulus in a sexually dimorphic manner. B6.Tg.sgk1 mice offer a particularly relevant opportunity to further analyze the involvement of this protein in nociception, and studies in models of chronic, neuropathic pain are warranted.
Mechanically-gated electrochemical ionic channels with chemically modified vertically aligned gold nanowires
2021, iScience
Mechanically-gated ion channels play an important role in the human body, whereas it is challenging to design artificial mechanically-controlled ionic transport devices as the intrinsically rigidity of traditional electrodes. Here, we report on a mechanically-gated electrochemical channel by virtue of vertically aligned gold nanowires (v-AuNWs) as 3D stretchable electrodes. By surface modification with a self-assembled 1-Dodecanethiol monolayer, the v-AuNWs become hydrophobic and inaccessible to hydrated redox species (e.g., ${Fe (CN)}_{6}^{3 - / 4 -}$ and ${Ru (bpy)}_{3}^{2 +}$ ). Under mechanical strains, the closely-packed v-AuNWs unzip/crack to generate ionic channels to enable redox reactions, giving rise to increases in Faradaic currents. The redox current increases with the strain level until it reaches a certain threshold value, and then decreases as the strain-induced conductivity decreases. The good reversible “on-off” behaviors for multiple cycles were also demonstrated. The results presented demonstrate a new strategy to control redox reactions simply by tensile strain, indicating the potential applications in future soft smart mechanotransduction devices.
Behavior and electrophysiology studies of the peripheral neuropathy induced by individual and co-administration of paclitaxel and oxaliplatin in rat
2021, Life Sciences
Antitumor agents, as taxanes and platinum compounds, induce peripheral neuropathies which can hamper their use for cancer treatment. The study of chemotherapy-induced neuropathies in humans is difficult because of ethical reasons, differences among administration protocols and intrinsic characteristics of patients. The aim of the present study is to compare the neuropathic signs induced by individual or combined administration of paclitaxel and oxaliplatin.
Oxaliplatin and paclitaxel were administered individually and combined to induce peripheral neuropathy in rats, sensory neuropathic signs were assessed in the hind limbs and orofacial area. The in vitro skin-saphenous nerve preparation was used to record the axonal activity of Aδ sensory neurons.
Animals treated with the combination developed mechanical allodynia in the paws and muscular hyperalgesia in the orofacial area, which was similar to that in animals treated with monotherapy, the latter also developed cold allodynia in the paws. Aδ-fibers of the rats treated with the combination were hyperexcited and presented hypersensitivity to pressure stimulation of the innervated skin, also similar to that recorded in the fibers of the animals treated with monotherapy.
Our work objectively demonstrates that the combination of a platinum compound with a taxane does not worsen the development of sensorial neuropathies in rats, which is an interesting data to take into account when the combination of antitumor drugs is necessary. Co-administration of antitumor drugs is more effective in cancer treatment without increasing the risk of the disabling neuropathic side effects.
Electrophysiological-mechanical coupling in the neuronal membrane and its role in ultrasound neuromodulation and general anaesthesia
2019, Acta Biomaterialia
The current understanding of the role of the cell membrane is in a state of flux. Recent experiments show that conventional models, considering only electrophysiological properties of a passive membrane, are incomplete. The neuronal membrane is an active structure with mechanical properties that modulate electrophysiology. Protein transport, lipid bilayer phase, membrane pressure and stiffness can all influence membrane capacitance and action potential propagation. A mounting body of evidence indicates that neuronal mechanics and electrophysiology are coupled, and together shape the membrane potential in tight coordination with other physical properties. In this review, we summarise recent updates concerning electrophysiological-mechanical coupling in neuronal function. In particular, we aim at making the link with two relevant yet often disconnected fields with strong clinical potential: the use of mechanical vibrations—ultrasound—to alter the electrophysiogical state of neurons, e.g., in neuromodulation, and the theories attempting to explain the action of general anaesthetics.
General anaesthetics revolutionised medical practice; now an apparently unrelated technique, ultrasound neuromodulation—aimed at controlling neuronal activity by means of ultrasound—is poised to achieve a similar level of impact. While both technologies are known to alter the electrophysiology of neurons, the way they achieve it is still largely unknown. In this review, we argue that in order to explain their mechanisms/effects, the neuronal membrane must be considered as a coupled mechano-electrophysiological system that consists of multiple physical processes occurring concurrently and collaboratively, as opposed to sequentially and independently. In this framework the behaviour of the cell membrane is not the result of stereotypical mechanisms in isolation but instead emerges from the integrative behaviour of a complexly coupled multiphysics system.
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Citation Excerpt :
The saphenous nerve was threaded into a mineral oil-filled recording chamber and placed on top of a small mirror for dissection. The nerve was de-sheathed and extracellular recordings were obtained from functionally identified single myelinated fibers in teased filaments draped over a silver hook electrode (Kress et al., 1992; Reeh, 1986). Signals were amplified, digitized, and recorded using Spike2 software for offline analysis.
Primary afferents are known to be inhibited by kappa opioid receptor (KOR) signaling. However, the specific types of somatosensory neurons that express KOR remain unclear. Here, using a newly developed KOR-cre knockin allele, viral tracing, single-cell RT-PCR, and ex vivo recordings, we show that KOR is expressed in several populations of primary afferents: a subset of peptidergic sensory neurons, as well as low-threshold mechanoreceptors that form lanceolate or circumferential endings around hair follicles. We find that KOR acts centrally to inhibit excitatory neurotransmission from KOR-cre afferents in laminae I and III, and this effect is likely due to KOR-mediated inhibition of Ca²⁺ influx, which we observed in sensory neurons from both mouse and human. In the periphery, KOR signaling inhibits neurogenic inflammation and nociceptor sensitization by inflammatory mediators. Finally, peripherally restricted KOR agonists selectively reduce pain and itch behaviors, as well as mechanical hypersensitivity associated with a surgical incision. These experiments provide a rationale for the use of peripherally restricted KOR agonists for therapeutic treatment.

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Sensory receptors in mammalian skin in an in vitro preparation

Abstract

Life Sci.

Brain Res.

Pain

Brain Res.

Pharmacological modulation of the discharge of nociceptive C-fibres