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

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.

1980 ◽  
Vol 44 (6) ◽  
pp. 1214-1225 ◽  
Author(s):  
J. K. Terzis ◽  
R. W. Dykes

1. A total of 758 fibers were isolated from previously transected and repaired ulnar nerves of five baboons. These fibers were compared to fibers from normal and previously crushed nerves studied in an earlier experiment. 2. The conduction velocities of the proximal portion of the injured axons dropped below normal, and this reduction persisted until reinnervation appeared nearly complete. 3. The receptive-field organization and response characteristics of 79 cutaneous afferent fibers serving the glabrous skin were studied in detail and compared to cutaneous afferent fibers of normal and previously crushed nerves studied earlier. 4. Initially, receptive fields were small and irregular, and often one fiber served several distinct skin regions. Ten months later, most of these abnormalities were no longer apparent. 5. Thresholds for single impulses elicited by von Frey hairs remained elevated for up to 4 mo after the receptive field reappeared, but then dropped abruptly to a near-normal range. 6. After reinnervation, rapidly adapting fibers displayed tuning curves characteristic of their submodality, but thresholds were elevated and only began to approach the normal range 6 mo after reinnervation. 7. After reinnervation, slowly adapting fibers displayed stimulus-response curves with elevated thresholds and they tended to saturate at lower stimulus intensities than normal fibers. 8. When compared to the return of function following a crushing injury, axons that had been transected displayed a slower time course for the return to normal values of conduction velocity and threshold. Receptive-field organization also remained abnormal for a longer time period. 9. These data support the hypotheses that a) breaking the continuity of the Schwann cells and extracellular matrix that occurs during transection but not during crush is a major factor leading to errors of axonal regeneration in the distal stump, b) submodality specificity is a property of the regenerating axon, and c) regenerating axons are influenced by an internal or external cue, causing them to form and maintain a single relatively homogeneous receptive field.


1986 ◽  
Vol 55 (4) ◽  
pp. 644-659 ◽  
Author(s):  
K. H. Sanders ◽  
M. Zimmermann

In the glabrous skin of the rat's hindfoot the same triple set of low-threshold mechanoreceptors is present as has been found in other mammals: slowly adapting (SA), rapidly adapting (RA), and very rapidly adapting Pacinian corpuscle-like (PC) receptors. Their functional characteristics were examined in normal rats and compared with those of sensitive mechanoreceptors found in the glabrous skin of the foot 2-24 wk after crush of the plantar nerves, resulting in regeneration of the transected nerve fibers. After 2 wk of nerve regeneration, low-threshold RA and SA cutaneous mechanoreceptors reappeared in the foot skin. Responses of PC receptors were recorded again after 3 wk, at which time the proportion of fibers that could be identified as low-threshold cutaneous mechanoreceptors had regained control level. Discharge patterns of regenerated cutaneous mechanosensitive receptors were very similar to those of normal skin mechanoreceptors. Their sensitivity to controlled mechanical stimulation was, however, still reduced 4 wk after the lesion. After 8 wk RA and SA receptors had regained their normal dynamic sensitivity, i.e., the responsiveness to the velocity of skin indentation. The static sensitivity of SA receptors, i.e., responsiveness to maintained skin indentation, was not consistently reestablished within 24 wk. No shift in sensitivity could be deduced from tuning curves of PC receptors examined 3-24 wk after nerve crush. In addition to the low-threshold mechanoreceptors, high-threshold (HT) mechanoreceptive fibers were found in controls and in animals with regenerating nerves. This type of fiber was most frequently found 1 wk after the nerve crush, when reinnervation of the foot started. They probably represent fibers not connected to specific mechanoreceptor end organs. Thus, functional restitution of the highly specific cutaneous mechanoreceptors occurs fairly soon after invasion of the original territory by the regenerating nerve. It is assumed that the underlying mechanism is the rapid reconnection of fibers with the end organs that have either survived during the period of denervation or regenerated subsequent to reinnervation of the skin.


2001 ◽  
Vol 85 (4) ◽  
pp. 1561-1574 ◽  
Author(s):  
David M. Cain ◽  
Sergey G. Khasabov ◽  
Donald A. Simone

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.


2001 ◽  
Vol 85 (5) ◽  
pp. 1793-1804 ◽  
Author(s):  
G. T. Coleman ◽  
H. Bahramali ◽  
H. Q. Zhang ◽  
M. J. Rowe

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.


2006 ◽  
Vol 203 (4) ◽  
pp. 933-940 ◽  
Author(s):  
Javier A. Carrero ◽  
Boris Calderon ◽  
Emil R. Unanue

Mice deficient in lymphocytes are more resistant than normal mice to Listeria monocytogenes infection during the early innate immune response. This paradox remains unresolved: lymphocytes are required for sterilizing immunity, but their presence during the early stage of the infection is not an asset and may even be detrimental. We found that lymphocyte-deficient mice, which showed limited apoptosis in infected organs, were resistant during the first four days of infection but became susceptible when engrafted with lymphocytes. Engraftment with lymphocytes from type I interferon receptor–deficient (IFN-αβR−/−) mice, which had reduced apoptosis, did not confer increased susceptibility to infection, even when the phagocytes were IFN-αβR+/+. The attenuation of innate immunity was due, in part, to the production of the antiinflammatory cytokine interleukin 10 by phagocytic cells after the apoptotic phase of the infection. Thus, immunodeficient mice were more resistant relative to normal mice because the latter went through a stage of lymphocyte apoptosis that was detrimental to the innate immune response. This is an example of a bacterial pathogen creating a cascade of events that leads to a permissive infective niche early during infection.


1995 ◽  
Vol 73 (2) ◽  
pp. 651-661 ◽  
Author(s):  
R. D. Johnson ◽  
J. S. Taylor ◽  
L. M. Mendell ◽  
J. B. Munson

1. In this study we investigate the peripheral receptive field properties and spinal cord connections of low-threshold muscle afferent fibers cross-regenerated into the skin to determine whether a cutaneous target can rescue physiological functions lost after chronic axotomy. 2. In adult cats the medial gastrocnemius (MG) muscle nerve was coated with the distal cut end of either the caudal or lateral cutaneous sural nerves and allowed to regenerate into the hairy skin (postoperative period 6-30 mo). During terminal acute experiments we made recordings of single MG afferent fibers in dorsal root filaments and peripheral nerve. Conduction velocity and receptive field characteristics were determined for each fiber. In addition, the MG nerve was stimulated to elicit cord dorsum potentials and monosynaptic excitatory postsynaptic potentials (EPSPs) in heteronymous motoneurons. As controls, studies were carried out after MG nerve axotomy (postoperative period 2.5-12 mo). 3. After innervation of the skin, MG muscle afferent fibers exhibited firing characteristics and proximal segment conduction velocities like those of normal MG afferents. Responses to skin and hair stimulation consisted primarily of slowly adapting, stretch-sensitive, and steady discharge patterns, all common in normal muscle afferents but not in cutaneous afferents. These properties were observed despite the innervation of touch domes and single hairs, suggesting that the peripheral physiology of muscle afferents is a function of the axonal membrane and is not respecified by a cutaneous target and/or receptors. 4. Cord dorsum potentials were characteristic of those elicited by intact muscle afferents rather than skin afferents and showed recovery of configurations lost after chronic axotomy. 5. The monosynaptic EPSPs elicited in lateral gastrocnemius-soleus motoneurons also recovered from the reduction in amplitude observed after chronic axotomy. The configurations of these EPSPs were characteristic of muscle afferents rather than skin afferents. 6. These experiments demonstrate that the peripheral and central physiological properties of muscle afferents are rescued from the axotomy state if the afferents are allowed to reinnervate skin. We found no evidence that respecification had occurred to bring the function of muscle afferents into accord with the new cutaneous target.


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