scholarly journals Innervation Territories of Mechano-Insensitive C Nociceptors in Human Skin

2002 ◽  
Vol 88 (4) ◽  
pp. 1859-1866 ◽  
Author(s):  
R. Schmidt ◽  
M. Schmelz ◽  
C. Weidner ◽  
H. O. Handwerker ◽  
H. E. Torebjörk
Keyword(s):  
Human Skin ◽  
Human Subjects ◽  
Receptive Fields ◽  
Healthy Human ◽  
Axon Reflex ◽  
Chemical Substances ◽  
Current Spread ◽  
Healthy Human Subjects ◽  
Median Area

Microneurographic recordings were obtained in the peroneal nerve from 20 mechano-insensitive units (CMi) and six mechano-heat responsive C units (CMH) in healthy human subjects. Their innervation territories in the skin of the leg or foot were assessed by transcutaneous electrical stimulation with a pointed probe at intensities of 10 to 100 mA (0.2 ms) and, when applicable, by mechanical von Frey hair stimulation. Electro-receptive fields (eRFs) of CMH units had a median area of 1.95 cm2 when mapped with 10 mA that coincided approximately with mechano-receptive fields (mRFs) as mapped with a 750-mN von Frey hair. Fifty-milliampere stimuli increased the eRFs to 3.08 cm2 in a concentric manner. This was probably due to current spread since these units are known to have low electrical thresholds. Further increase of the stimulus strength to 70 or 100 mA increased the eRFs only marginally. Mechano-insensitive units had much smaller eRFs (median: 0.35 cm2) than CMH units when mapped with the same pointed probe at 10 mA ( n = 13). The receptive territories consisted of one distinct spot or of several spots separated by distances of more than 1 cm. However, when mapping stimuli of 50 mA were applied, eRFs became continuous and grew to a median area of 5.34 cm2, i.e., larger than those of CMHs. The borders of eRFs of CMi units were significantly more irregular compared with CMH units. A further increase of the stimulus intensity to a maximum of 100 mA only marginally enlarged the eRFs. The CMi units could be activated by heat or chemical substances applied inside the 50-mA eRF, indicating that receptive nerve endings were mapped. Responsiveness to these stimuli was inhomogeneous within the eRFs. It was concluded that innervation territories of CMi units in human skin exceed those of CMH units in size by a factor of approximately 3. The widely branched terminals underlying the large fields are consistent with a role of this nociceptor class in axon reflex flare and preclude a role in exact spatial discrimination of noxious stimuli.

Abstract 420: Exploring the Role of TNFα in TLR4-/NLPR3 Inflammasome-driven Inflammation in Humans

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Matthijs Moerland ◽  
Karen Malone ◽  
Marlous Dillingh ◽  
Wieke Grievink ◽  
Joannes Reijers ◽  
...  
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Human Subjects ◽  
Healthy Human ◽  
Mechanistic Investigation ◽  
Healthy Human Subjects ◽  
Key Factor ◽  
Culture Supernatants

The role of TNFα in the pathogenesis of atherosclerosis is incompletely understood. TNFα blockade reduces the severity of various autoimmune diseases and the often related atherosclerosis. However, excessively released TNFα is only one component of the hyperactive innate immune system in such diseases. To provide more insight into the role of TNFα in the induction of inflammation, we explored the effects of TNFα blockade in human whole blood. TLR4/NLPR3 inflammasome challenges were applied to induce an inflammatory response. For this purpose, whole blood was incubated 4 hours with LPS and aluminium hydroxide (Alhydrogel). TNFα blockade was evaluated in vitro (LPS/Alhydrogel challenge in whole blood of 4 healthy human subjects, +concentration range of adalimumab) and ex vivo (LPS/Alhydrogel challenge in whole blood of 13 healthy human subjects receiving a single subcutaneous (sc) dose of 40 mg adalimumab). Cytokine release was evaluated in culture supernatants. In vitro, TNFα blockade strongly reduced TNFα levels detected; -97±1% at the lowest adalimumab concentration (0.3125 μg/mL). TNFα blockade did not affect LPS/Alhydrogel-induced IL-6, IL-1β and IL-18 release, but reduced IFNγ release; maximally -93±4% at 5 μg/mL adalimumab. A single sc adalimumab dose in healthy subjects reduced LPS/Alhydrogel-induced TNFα levels (maximally -98±1% on day 4, and still -58±59% on day 64; versus baseline). IL-6, IL-1β and IL-8 release were not reduced after anti-TNFα treatment. The effect of TNFα blockade on IFNγ release could not be reliably estimated due to highly variable IFNγ levels, especially between genders (baseline IFNγ levels 1248±1771 and 140±283 pg/mL, males vs females). TNFα is a major inducer of NFκB-driven cytokine gene transcription, but TNFα blocking did not reduce LPS/Alhydrogel-induced release of IL-1β, IL-6, IL-8 or IL-18 by primary human cells. This suggests that primary TLR4- and inflammasome-mediated signalling is sufficient to drive secretion of these cytokines. However, in vitro TNFα blockade did impair IFNγ release. Since IFNγ is a key factor in atherogenesis, exerting both pro- and anti-atherogenic properties, our data warrant further mechanistic investigation of the role of TNFα and anti-TNFα therapies in atherosclerosis.

scholarly journals The role of energy content of a meal on gastrointestinal transit in healthy human subjects

2000 ◽  
Vol 118 (4) ◽  
pp. A390
Author(s):  
Lukas Degen ◽  
Daniel Matzinger ◽  
Helmut Maecke ◽  
Christoph Beglinger
Keyword(s):  
Energy Content ◽  
Human Subjects ◽  
Gastrointestinal Transit ◽  
Healthy Human ◽  
Healthy Human Subjects

Innervation Territories of Mechanically Activated C Nociceptor Units in Human Skin

1997 ◽  
Vol 78 (5) ◽  
pp. 2641-2648 ◽  
Author(s):  
Roland Schmidt ◽  
Martin Schmelz ◽  
Matthias Ringkamp ◽  
Hermann O. Handwerker ◽  
H. Erik Torebjörk
Keyword(s):  
Human Skin ◽  
Peroneal Nerve ◽  
Human Subjects ◽  
Receptive Fields ◽  
Spatial Summation ◽  
Lower Leg ◽  
Mechanical Stimuli ◽  
Axon Reflex ◽  
C Fibers ◽  
Noxious Stimuli

Schmidt, Roland, Martin Schmelz, Matthias Ringkamp, Hermann O. Handwerker, and H. Erik Torebjörk. Innervation territories of mechanically activated C nociceptor units in human skin. J. Neurophysiol. 78: 2641–2648, 1997. Innervation territories of single mechanically activated C nociceptors in the skin of the leg and foot were explored in normal human subjects. Microneurographic recordings were obtained in the peroneal nerve from 70 mechano-heat responsive (CMH) and 7 mechano-(but not heat) responsive (CM) units. Units were identified by their constant long-latency response to intracutaneous electrical stimulation of their terminals. Responsiveness to mechanical, heat, or transcutaneous electrical stimuli was verified by transient slowing of conduction velocity after activation by such stimuli. We determined their thresholds to mechanical stimuli (mean 33.7 mN, median 30 mN, range 3–750 mN) and heat (mean 42.5°C, median 42.5°C, range 37–49°C). Most mechano-receptive fields (mRFs) were found on the foot dorsum (60 units) and some on the lower leg (14 units) and toes (3 units). Most units had one continuous mRF, but 10 units had more complex fields. Areas of mRFs mapped with a von Frey filament (750 mN) ranged from 10 to 363 mm2 (mean, 106 mm2). The mRFs were oval or irregularly shaped with greatest diameters ranging from 3 to 45 mm. Mean areas of mRFs were largest on the lower leg (198 mm2), smaller on the foot dorsum (88 mm2), and smallest on the toes (35 mm2). Forty-nine of the 77 units had identical mRFs and electro-receptive fields (eRFs). Twenty-six units had larger eRFs than mRFs, whereas the opposite was found for two units only. Areas of eRFs ranged from 16 to 511 mm2 (mean 121 mm2). An estimate of the innervation density based on the present data and the presumed number of C fibers in cutaneous fascicles of the peroneal nerve suggests a considerable overlap of nociceptive endings in the skin. Such overlapping nociceptor innervation in the skin allows for substantial spatial summation in response to punctate noxious stimuli, which may be a prerequisite for high accuracy in localizing painful events from a C-fiber input. The reduction in size of innervation territories distally allows for finer discrimination of spatial dimensions of noxious stimuli distally as compared with proximal regions of the extremities. Mean maximal diameters of the mechano-receptive fields of CMH and CM units on the lower leg (22.3 mm) and foot (15.3 mm) are of similar size as the radius of axon reflex flares evoked by noxious mechanical stimuli in these regions.

Evidence for a Role of the Cerebellum in the Regulation of Impulsive Behaviour in Healthy Human Subjects

NeuroImage ◽  
2009 ◽  
Vol 47 ◽  
pp. S189
Author(s):  
A Bohringer ◽  
D Margulies ◽  
B Pleger ◽  
H Walz ◽  
F Busse ◽  
...  
Keyword(s):  
Human Subjects ◽  
Healthy Human ◽  
Impulsive Behaviour ◽  
Healthy Human Subjects

scholarly journals The role of vestibular cues in postural sway

2021 ◽  
Vol 125 (2) ◽  
pp. 672-686
Author(s):  
Faisal Karmali ◽  
Adam D. Goodworth ◽  
Yulia Valko ◽  
Tania Leeder ◽  
Robert J. Peterka ◽  
...  
Keyword(s):  
Postural Control ◽  
Postural Sway ◽  
Balance Control ◽  
Human Subjects ◽  
Healthy Human ◽  
Lateral Translation ◽  
Vestibular Cues ◽  
Healthy Human Subjects ◽  
Vestibular Pathology

Vestibular feedback is important for postural control, but little is known about the role of tilt cues vs. translation cues vs. rotation cues. We studied healthy human subjects with no known vestibular pathology or symptoms. Our findings showed that vestibular encoding of lateral translation correlated with medial-lateral postural sway, consistent with lateral translation cues contributing to balance control. This adds support to the hypothesis that vestibular noise contributes to spontaneous postural sway.

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