Response Properties of Mechanoreceptors and Nociceptors in Mouse Glabrous Skin: An In Vivo Study

2001 ◽  
Vol 85 (4) ◽  
pp. 1561-1574 ◽  
Author(s):  
David M. Cain ◽  
Sergey G. Khasabov ◽  
Donald A. Simone
Keyword(s):  
Transgenic Mice ◽  
Somatosensory System ◽  
Glabrous Skin ◽  
In Vivo Study ◽  
Response Properties ◽  
C Fibers ◽  
Afferent Fibers ◽  
Response Thresholds ◽  
Thermal Stimuli

The increasing use of transgenic mice for the study of pain mechanisms necessitates comprehensive understanding of the murine somatosensory system. Using an in vivo mouse preparation, we studied response properties of tibial nerve afferent fibers innervating glabrous skin. Recordings were obtained from 225 fibers identified by mechanical stimulation of the skin. Of these, 106 were classed as Aβ mechanoreceptors, 51 as Aδ fibers, and 68 as C fibers. Aβ mechanoreceptors had a mean conduction velocity of 22.2 ± 0.7 (SE) m/s (13.8–40.0 m/s) and a median mechanical threshold of 2.1 mN (0.4–56.6 mN) and were subclassed as rapidly adapting (RA, n = 75) or slowly adapting (SA, n = 31) based on responses to constant force mechanical stimuli. Conduction velocities ranged from 1.4 to 13.6 m/s (mean 7.1 ± 0.6 m/s) for Aδ fibers and 0.21 to 1.3 m/s (0.7 ± 0.1 m/s) for C fibers. Median mechanical thresholds were 10.4 and 24.4 mN for Aδ and C fibers, respectively. Responses of Aδ and C fibers evoked by heat (35–51°C) and by cold (28 to −12°C) stimuli were determined. Mean response thresholds of Aδ fibers were 42.0 ± 3.1°C for heat and 7.6 ± 3.8°C for cold, whereas mean response thresholds of C fibers were 40.3 ± 0.4°C for heat and 10.1 ± 1.9°C for cold. Responses evoked by heat and cold stimuli increased monotonically with stimulus intensity. Although only 12% of tested Aδ fibers were heat sensitive, 50% responded to cold. Only one Aδ nociceptor responded to both heat and cold stimuli. In addition, 40% of Aδ fibers were only mechanosensitive since they responded neither to heat nor to cold stimuli. Thermal stimuli evoked responses from the majority of C fibers: 82% were heat sensitive, while 77% of C fibers were excited by cold, and 68% were excited by both heat and cold stimuli. Only 11% of C fibers were insensitive to heat and/or cold. This in vivo study provides an analysis of mouse primary afferent fibers innervating glabrous skin including new information on encoding of noxious thermal stimuli within the peripheral somatosensory system of the mouse. These results will be useful for future comparative studies with transgenic mice.

scholarly journals Role of c-Fos in orthodontic tooth movement: an in vivo study using transgenic mice

2020 ◽  
Author(s):  
Maximilian G. Decker ◽  
Cita Nottmeier ◽  
Julia Luther ◽  
Anke Baranowsky ◽  
Bärbel Kahl-Nieke ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
In Vivo Study

scholarly journals Differential heat shock gene hsp70-1 response to toxicants revealed by in vivo study of lungs in transgenic mice

2002 ◽  
Vol 7 (4) ◽  
pp. 387 ◽  
Author(s):  
Delphine Wirth ◽  
Elisabeth Christians ◽  
Carine Munaut ◽  
Cécile Dessy ◽  
Jean-Michel Foidart ◽  
...  
Keyword(s):  
Heat Shock ◽  
Transgenic Mice ◽  
In Vivo Study ◽  
Heat Shock Gene ◽  
Differential Heat ◽  
Shock Gene

Characterization of Tactile Afferent Fibers in the Hand of the Marmoset Monkey

2001 ◽  
Vol 85 (5) ◽  
pp. 1793-1804 ◽  
Author(s):  
G. T. Coleman ◽  
H. Bahramali ◽  
H. Q. Zhang ◽  
M. J. Rowe
Keyword(s):  
Somatosensory System ◽  
Macaque Monkey ◽  
Glabrous Skin ◽  
Human Hand ◽  
Type I ◽  
Marmoset Monkey ◽  
Afferent Fibers ◽  
Wide Range ◽  
Static Indentation ◽  
Functional Classes

The marmoset monkey, Callithrix jacchus, has increasingly been the subject of experiments for the analysis of somatosensory system function in simian primates. However, as response properties of the mechanoreceptive afferent fibers supplying the skin have not been characterized for this primate, the present study was undertaken to classify fibers innervating the glabrous skin of the marmoset hand and determine whether they resembled those described for other mammalian species, including cat, macaque monkey, and human subjects. Forty-seven tactile afferent fibers with receptive fields (RFs) on the glabrous skin of the hand were isolated in fine median and ulnar nerve strands. Controlled tactile stimuli, including static indentation and skin vibration, were used to classify fibers. Twenty-six (55%) responded to static indentation in a sustained manner and were designated slowly adapting (SA) fibers, while 21 (45%) were selectively sensitive to the dynamic components of the stimulus. The SA fibers had well-defined boundaries to their RFs, lacked spontaneous activity in most cases (23/26 fibers), had an irregular pattern of discharge to static skin indentation, and displayed graded response levels as a function of indentation amplitude, attributes that were consistent with the properties of slowly adapting type I (SAI) fibers described in other species. The dynamically sensitive afferent fibers could be subdivided into two distinct functional classes, based on their responses to vibrotactile stimulation. The majority (15/21) responded best to lower frequency vibration (∼10–50 Hz) and had small RFs, whereas the second class responded preferentially to higher frequency vibration (50–700 Hz) with maximal sensitivity at ∼200–300 Hz. These two classes resembled, respectively, the rapidly adapting (RA) and Pacinian corpuscle–related (PC) fiber classes found in other species, and like them, responded to vibration with tightly phase-locked patterns of response over a wide range of frequencies. The results demonstrate that the functional classes of tactile afferent fibers that supply the glabrous skin in the marmoset monkey appear to correspond with those described previously for the cat and macaque monkey, and are similar to those supplying the human hand and fingers, although the SA fibers in the human hand appear to fall into two classes, the SAI and SAII fibers. With the increasing use of the marmoset monkey as a primate model for somatosensory system studies, these data now allow tactile neurons identified at central locations, such as the cerebral cortex and thalamus, to be classified in relation to inputs from the peripheral classes identified in the present study.

Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro

1992 ◽  
Vol 68 (2) ◽  
pp. 581-595 ◽  
Author(s):  
M. Kress ◽  
M. Koltzenburg ◽  
P. W. Reeh ◽  
H. O. Handwerker
Keyword(s):  
Mustard Oil ◽  
In Vitro Experiments ◽  
Unmyelinated Fibers ◽  
C Fibers ◽  
Significant Difference ◽  
Cold Sensitive ◽  
Sympathetic Efferents ◽  
Thermal Stimuli

1. The purpose of the present study was to compare the responsiveness unmyelinated cutaneous units in vivo and in vitro and to determine the proportion of primary afferents innervating the rat hairy skin that do not respond to transient mechanical or thermal stimuli. We have adopted electrical search strategies to locate the terminal arborization of unmyelinated fibers before testing the sensitivity to adequate stimuli. 2. A total of 144 unmyelinated units were studied, of which 31 were obtained from in vivo and 113 from in vitro experiments. 55 afferents were investigated after chronic surgical sympathectomy. Units recorded from sympathectomized rats did not differ in their conduction velocity, electrical thresholds, or receptive properties from units in intact animals. 3. There were only minor differences between the properties of units recorded in vivo and in vitro. This probably reflects technical differences of the setups rather than biological changes introduced by the in vitro conditions. Except for a higher prevalence of mechano-cold sensitive units in vitro, there was no significant difference between the distributions of receptor types. 4. Eight of 31 units (26%) recorded in vivo and 17 of 113 units (15%) obtained from in vitro experiments failed to respond to transient mechanical or thermal stimuli. In vivo, one of eight initially unresponsive units was activated by repeated mechanical and thermal stimulation. Two further units became responsive after topical application of mustard oil. In vitro, 2 of 17 unresponsive units were activated by repeated stimulation. Ten of the remaining unresponsive units were treated with a combination of inflammatory mediators. Four of these units were activated: three developed ongoing activity, and two of them also became responsive to mechanical and/or heat stimuli. The fourth unit responded to probing but was not spontaneously active. 5. We conclude that transient mechanical or thermal stimuli can excite the majority of unmyelinated cutaneous units. However, in vivo and in vitro, part of unmyelinated units are initially unresponsive even to noxious forms of stimulation. Because those unresponsive units were also encountered in sympathectomized preparations, and because some units can be recruited with repeated noxious stimuli or inflammatory agents, it is unlikely that all of them are sympathetic efferents. The same substances that cause sensitization of "normal" nociceptors are capable of recruiting initially unresponsive unmyelinated afferents.

Speed and Temperature Dependences of Mechanotransduction in Afferent Fibers Recorded From the Mouse Saphenous Nerve

2008 ◽  
Vol 100 (5) ◽  
pp. 2771-2783 ◽  
Author(s):  
Nevena Milenkovic ◽  
Christiane Wetzel ◽  
Rabih Moshourab ◽  
Gary R. Lewin
Keyword(s):  
Saphenous Nerve ◽  
Conduction Delay ◽  
Response Functions ◽  
Response Properties ◽  
Stimulus Response ◽  
C Fibers ◽  
Afferent Fibers ◽  
Temperature Dependences ◽  
Different Temperatures ◽  
Almost All

Here we have systematically characterized the stimulus response properties of mechanosensitive sensory fibers in the mouse saphenous nerve. We tested mechanoreceptors and nociceptors with defined displacement stimuli of varying amplitude and velocity. For each sensory afferent investigated we measured the mechanical latency, which is the delay between the onset of a ramp displacement and the first evoked spike, corrected for conduction delay. Mechanical latency plotted as a function of stimulus strength was very characteristic for each receptor type and was very short for rapidly adapting mechanoreceptors (<11 ms) but very long in myelinated and unmyelinated nociceptors (49–114 ms). Increasing the stimulus speed decreased mechanical latency in all receptor types with the notable exception of C-fiber nociceptors, in which mean mechanical latency was not reduced ≲100 ms, even with very fast ramp stimuli (2,945 μm/s). We examined stimulus response functions and mechanical latency at two different temperatures (24 and 32°C) and found that stimulus response properties of almost all mechanoreceptors were not altered in this range. A notable exception to this rule was found for C-fibers in which mechanical latency was substantially increased and stimulus response functions decreased at lower temperatures. We calculated Q10 values for mechanical latency in C-fibers to be 5.1; in contrast, the Q10 value for conduction velocity for the same fibers was 1.4. Finally, we examined the effects of short-term inflammation (2–6 h) induced by carrageenan on nociceptor and mechanoreceptor sensitivity. We did not detect robust changes in mechanical latency or stimulus response functions after inflammation that might have reflected mechanical sensitization under the conditions tested.

An in vitro and in vivo study of early deficits in associative learning in transgenic mice that over-express a mutant form of human APP associated with Alzheimer's disease

2004 ◽  
Vol 20 (7) ◽  
pp. 1945-1952 ◽  
Author(s):  
Eduardo Dominguez-del-Toro ◽  
Antonio Rodriguez-Moreno ◽  
Elena Porras-Garcia ◽  
Raudel Sanchez-Campusano ◽  
Veronique Blanchard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Associative Learning ◽  
In Vivo Study ◽  
Mutant Form

Receptive Properties of Embryonic Chick Sensory Neurons Innervating Skin

1997 ◽  
Vol 78 (5) ◽  
pp. 2560-2568 ◽  
Author(s):  
Martin Koltzenburg ◽  
Gary R. Lewin
Keyword(s):  
Sensory Neurons ◽  
Axon Growth ◽  
Embryonic Chick ◽  
Sensory Afferents ◽  
Noxious Heat ◽  
C Fibers ◽  
Afferent Fibers ◽  
Mechanical Thresholds

Koltzenburg, Martin and Gary R. Lewin. Receptive properties of embryonic chick sensory neurons innervating skin. J. Neurophysiol. 78: 2560–2568, 1997. We describe a new in vitro skin-nerve preparation from chick embryos that allows detailed study of the functional properties of developing sensory neurons innervating skin. Functionally single sensory afferents were isolated by recording from their axons in microdissected filaments of the cutaneous femoralis medialis nerve, which innervates skin of the thigh. A total of 157 single neurons were characterized from embryos [embryonic days 17–21 ( E17–E21), n = 115] and hatchlings up to 3 wk old ( n = 42). Neurons were initially classified on the basis of their conduction velocity; those conducting below 1.0 m/s were being classified as C fibers and faster conducting fibers as A fibers. The proportions of A and C fibers encountered in embryonic and hatchling preparations were not very different, indicating that myelination and axon growth proceeds quite slowly over the period studied. Afferent fibers that could subserve nociceptive and nonnociceptive functions were identified in the time period studied. Subpopulations of low-threshold myelinated afferent units exhibited rapidly or slowly adapting discharges to constant force stimuli and could have tactile functions. Many afferent fibers responded to noxious heat and were excited and sensitized by exposure to inflammatory mediators, suggesting that they are nociceptors. The behavior of these units changed in several respects over the period studied. The discharge of C fibers to noxious heat increased with age as did their mechanical thresholds. A substantial population of heat-responsive neurons (34% of the A fibers) present in embryos were not encountered in hatchling chicks. This indicates that substantial changes in the physiological response properties of sensory afferents occur after hatching. We conclude that this new preparation can be used for quantitative assessment of the receptive properties of developing sensory neurons and has considerable potential for the investigation of factors, such as neurotrophins, that specify and influence the functional phenotype of sensory neurons during embryonic development in vivo.

scholarly journals Selective Activation of Primary Afferent Fibers Evaluated by Sine-Wave Electrical Stimulation

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-13 ◽  
Author(s):  
Kohei Koga ◽  
Hidemasa Furue ◽  
Md Harunor Rashid ◽  
Atsushi Takaki ◽  
Toshihiko Katafuchi ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Stimulus Frequency ◽  
Sine Wave ◽  
Drg Neurons ◽  
Functional Changes ◽  
C Fibers ◽  
Afferent Fibers ◽  
Painful Sensation ◽  
Aβ Fibers

Transcutaneous sine-wave stimuli at frequencies of 2000, 250 and 5 Hz (Neurometer) are thought to selectively activate Aβ, Aδ and C afferent fibers, respectively. However, there are few reports to test the selectivity of these stimuli at the cellular level. In the present study, we analyzed action potentials (APs) generated by sine-wave stimuli applied to the dorsal root in acutely isolated rat dorsal root ganglion (DRG) preparations using intracellular recordings. We also measured excitatory synaptic responses evoked by transcutaneous stimuli in substantia gelatinosa (SG) neurons of the spinal dorsal horn, which receive inputs predominantly from C and Aδ fibers, using in vivo patch-clamp recordings. In behavioral studies, escape or vocalization behavior of rats was observed with both 250 and 5 Hz stimuli at intensity of ∼0.8 mA (T5/ T250), whereas with 2000 Hz stimulation, much higher intensity (2.14 mA, T2000) was required. In DRG neurons, APs were generated at T5/T250 by 2000 Hz stimulation in Aβ, by 250 Hz stimulation both in Aβ and Aδ, and by 5 Hz stimulation in all three classes of DRG neurons. However, the AP frequencies elicited in Aβ and Aδ by 5 Hz stimulation were much less than those reported previously in physiological condition. With in vivo experiments large amplitude of EPSCs in SG neurons were elicited by 250 and 5 Hz stimuli at T5/ T250. These results suggest that 2000 Hz stimulation excites selectively Aβ fibers and 5 Hz stimulation activates noxious transmission mediated mainly through C fibers. Although 250 Hz stimulation activates both Aδ and Aβ fibers, tactile sensation would not be perceived when painful sensation is produced at the same time. Therefore, 250 Hz was effective stimulus frequency for activation of Aδ fibers initiating noxious sensation. Thus, the transcutaneous sine-wave stimulation can be applied to evaluate functional changes of sensory transmission by comparing thresholds with the three stimulus frequencies.

Reinnervation of glabrous skin in baboons: properties of cutaneous mechanoreceptors subsequent to nerve crush

1979 ◽  
Vol 42 (5) ◽  
pp. 1461-1478 ◽  
Author(s):  
R. W. Dykes ◽  
J. K. Terzis
Keyword(s):  
Receptive Field ◽  
Early Stage ◽  
Normal Skin ◽  
Glabrous Skin ◽  
Type I ◽  
Cutaneous Mechanoreceptors ◽  
Nerve Crush ◽  
Response Properties ◽  
Afferent Fibers ◽  
Cutaneous Afferent Fibers

1. A total of 791 fibers were isolated from the ulnar nerves of five baboons. Over half of these were obtained from the right ulnar nerves subsequent to reinnervation following a nerve crush; the other fibers were obtained from the undamaged left ulnar nerves. 2. The conduction velocities in the proximal portion of the injured axons dropped below normal, and this reduction persisted until reinnervation appeared nearly complete. 3. The response properties of 65 cutaneous afferent fibers serving reinnervated glabrous skin were compared to 80 fibers from normal skin. 4. Of the afferent fibers reinnervating skin, the proportion judged to have abnormal response properties was not significantly greater than the proportion in normal skin. 5. After reinnervation, cutaneous rapidly adpating fibers displayed tuning curves characteristic of their submodality, while some cutaneous slowly adapting fibers could still be differentiated into type I and type II fibers. However, both types of slowly adapting fibers displayed an increased rate of adaptation and a lowered sensitivity to sustained displacements even at 5 mo following reinnervation. 6. In conclusion, the cutaneous mechanoreceptors in reinnervated glabrous skin regained response properties that allowed them to be assigned to the same submodalities found in normal skin. Submodality was recognizable at an early stage when the receptive field was still immature and when the threshold was elevated. With time, the receptive-field sizes and shapes returned to normal, the thresholds approached normal, and the remaining differences from normal cutaneous afferent fibers became minor.

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