Thermosensitivity of acutely axotomized sensory nerve fibers

1996 ◽  
Vol 76 (2) ◽  
pp. 743-752 ◽  
Author(s):  
K. H. Blenk ◽  
M. Michaelis ◽  
C. Vogel ◽  
W. Janig

1. Thermosensitivity of axotomized myelinated and unmyelinated fibers in the sural nerve was examined in anesthetized rats within 24 h after nerve ligation and transection. Activity in single fibers was recorded extracellularly from small filaments dissected from the nerve approximately 20-30 mm proximal to the lesioned site. Cold and warm stimuli were applied to the ligated and cut nerve end or 5-10 mm further proximal. 2. Among 871 unmyelinated fibers tested, 40 were excited by cooling of the cut and ligated nerve end (8-15 degrees C), 44 were excited by warming (35-65 degrees C), and 16 were both cold and warm sensitive. None of the 438 myelinated fibers investigated were activated by either cold or warm stimuli. 3. Cold- and warm-sensitive fibers responded in a graded fashion to thermal stimuli of variable temperatures. Between 11 and 30 degrees C, the responses of cold-sensitive fibers increased when the temperature was reduced. Responses of warm-sensitive fibers increased between 40 and 65 degrees C, when the temperature was increased. 4. Thermosensitive fibers displayed characteristic response profiles. Responses to cold stimuli were maximal at the beginning and decreased continuously to lower discharge frequencies as the stimuli were maintained. The stimulus-response curves to warm stimuli were bell-shaped and discharge frequencies were maximal after 5-15 s. 5. In some cold-sensitive fibers a spatial gradient of excitability emerged after axotomy. Maximal responses to isothermal stimuli were observed at the transection site, whereas the excitability declined when the thermal stimuli were applied 5 and 10 mm further proximal. 6. After axotomy, 190 unmyelinated fibers were exposed to cold and warm stimuli at two sites 5 and 10 mm proximal of the nerve stump, and 172 intact C fibers were stimulated at anatomically comparable sites along the nerve. No statistically significant difference was found between the prevalences of thermosensitivity of C fibers along their axons in these two groups (7 of 172 vs. 11 of 190). 7. In conclusion, some unmyelinated fibers can be ectopically excited by thermal stimuli within 24 h after nerve cut and ligation. This ectopically evoked activity may contribute to the generation of paresthesias, painful sensations, and associated changes following peripheral nerve lesion.

1992 ◽  
Vol 68 (2) ◽  
pp. 581-595 ◽  
Author(s):  
M. Kress ◽  
M. Koltzenburg ◽  
P. W. Reeh ◽  
H. O. Handwerker

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.


1995 ◽  
Vol 74 (3) ◽  
pp. 1020-1027 ◽  
Author(s):  
M. Michaelis ◽  
K. H. Blenk ◽  
W. Janig ◽  
C. Vogel

1. Spontaneous activity and ectopic mechanical excitability of axotomized unmyelinated and myelinated fibers in the sural nerve were examined in anesthetized rats. The analysis was performed within 30 h after the nerve lesion using single-fiber recordings that were performed proximal to the severed nerve end. 2. Among all unmyelinated fibers tested (n = 865), 4-8% exhibited persistent spontaneous activity of low and irregular frequency. The percentage of spontaneously active C fibers did not change significantly during the first 30 h. Only 6 of 796 A fibers had spontaneous activity. 3. Mechanical stimulation of the cut nerve end excited 5-8% of all C fibers under investigation. No development with time could be detected in the frequency of mechanically excitable C fibers. In contrast, beginning 6 h after nerve transection, the number of mechanically excitable A fibers rose with time, reaching 27% after 22-30 h. 4. Among the A fibers (C fibers) that exhibited mechanical excitability or spontaneous activity, only 4% (25%) had both properties, whereas 96% (75%) were either mechanosensitive or spontaneously active. 5. With time after the nerve lesion, the mean discharge rate of all spontaneously discharging C fibers decreased significantly from 49 imp/min (0.5-9 h after nerve lesion) to 11 imp/min after 22-30 h. The mean discharge rate of C fibers exhibiting solely spontaneous activity and those C fibers that were additionally mechanosensitive did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)


Author(s):  
James M. Kerns ◽  
James S. Walter ◽  
Michael J. Patetta ◽  
Anshum Sood ◽  
Awais K. Hussain ◽  
...  

Abstract Background Wallerian degeneration (WD) following peripheral nerve injury (PNI) is an area of growing focus for pharmacological developments. Clinically, WD presents challenges in achieving full functional recovery following PNI, as prolonged denervation of distal tissues for an extended period of time can irreversibly destabilize sensory and motor targets with secondary tissue atrophy. Our objective is to improve upon histological assessments of WD. Methods Conventional methods utilize a qualitative system simply describing the presence or absence of WD in nerve fibers. We propose a three-category assessment that allows more quantification: A fibers appear normal, B fibers have moderate WD (altered axoplasm), and C fibers have extensive WD (myelin figures). Analysis was by light microscopy (LM) on semithin sections stained with toluidine blue in three rat tibial nerve lesion models (crush, partial transection, and complete transection) at 5 days postop and 5 mm distal to the injury site. The LM criteria were verified at the ultrastructural level. This early outcome measure was compared with the loss of extensor postural thrust and the absence of muscle atrophy. Results The results showed good to excellent internal consistency among counters, demonstrating a significant difference between the crush and transection lesion models. A significant decrease in fiber density in the injured nerves due to inflammation/edema was observed. The growth cones of regenerating axons were evident in the crush lesion group. Conclusion The ABC method of histological assessment is a consistent and reliable method that will be useful to quantify the effects of different interventions on the WD process.


1991 ◽  
Vol 70 (5) ◽  
pp. 2087-2094 ◽  
Author(s):  
E. M. App ◽  
G. T. De Sanctis ◽  
F. H. Green ◽  
W. C. Hulbert ◽  
B. K. Rubin ◽  
...  

Full methacholine dose-response curves were performed on anesthetized tracheostomized Fischer 344 adult rats treated neonatally with capsaicin (50 mg/kg) or with vehicle alone. Capsaicin, the hot extract of pepper, releases substance P (SP) from nonmyelinated sensory nerve endings and causes acute bronchoconstriction and airway microvascular leakiness. Chronic treatment with capsaicin leads to depletion of SP and other tachykinins from afferent C-fibers and can therefore be used as a tool to investigate the contribution of SP innervation to airway responses. The rats (9 controls and 6 treated with capsaicin) were paralyzed with succinylcholine and mechanically ventilated at a constant tidal volume and frequency. Airway resistance (RL) and dynamic compliance (Cdyn) were determined at each dose of methacholine from measurements of volume, flow, and transpulmonary pressure. Capsaicin-treated rats were found to have a significantly reduced baseline RL [0.150 +/- 0.039 (SD) vs. 0.225 +/- 0.050 cmH2O.ml-1.s, P = 0.009] and a correspondingly significantly elevated Cdyn (0.371 +/- 0.084 vs. 0.268 +/- 0.053 ml/cmH2O, P = 0.012). There was no significant difference in sensitivity to methacholine, but the maximal response to methacholine was significantly greater in the capsaicin-treated rats. In terms of RL, the maximal response for capsaicin-treated rats was 6.03 x baseline +/- 0.98 vs. 4.30 x baseline +/- 1.80 (P = 0.05) for controls, and for Cdyn changes the maximal decrease was 5.75 x baseline +/- 1.22 vs. 3.83 +/- 0.69 (P = 0.002). The observed differences in RL and Cdyn coupled with the differences in maximal responses can be attributed to the selective destruction of a subpopulation of pulmonary afferent C-fibers.(ABSTRACT TRUNCATED AT 250 WORDS)


1994 ◽  
Vol 266 (1) ◽  
pp. L23-L29 ◽  
Author(s):  
R. S. Sakae ◽  
A. S. Leme ◽  
M. Dolhnikoff ◽  
P. M. Pereira ◽  
M. do Patrocinio ◽  
...  

We studied the effects of selective depletion of neurokinins in sensory nerve fibers by capsaicin treatment on the airway and pulmonary tissue responses to methacholine. Dose-response curves to aerosolized methacholine were performed on anesthetized and mechanically ventilated Wistar rats. Capsaicin (50 mg/kg sc) was administered to 2-day-old rats, and the animals were studied after 12 wk. The response to each dose of methacholine was determined by measuring changes in airway resistance (R(aw)), dynamic pulmonary elastance (Edyn), and pulmonary tissue resistance (Rtis). We calculated sensitivity (Kx) as the concentration of methacholine required for a one-half maximal response and reactivity as the relationship between the maximum response and Kx. Capsaicin treatment resulted in significantly greater values of Kx and lower values of reactivity for R(aw), Edyn, and Rtis compared with control rats. Morphometric analysis of airways showed similar values of the area occupied by smooth muscle but a significantly lower (P < 0.02) area of airway epithelium in capsaicin-treated rats. Our results suggest that methacholine requires capsaicin-sensitive nerves for part of its airway and lung tissue effects.


2014 ◽  
Vol 111 (10) ◽  
pp. 2071-2083 ◽  
Author(s):  
Alina Teliban ◽  
Fabian Bartsch ◽  
Marek Struck ◽  
Ralf Baron ◽  
Wilfrid Jänig

Intact and injured cutaneous C-fibers in the rat sural nerve are cold sensitive, heat sensitive, and/or mechanosensitive. Cold-sensitive fibers are either low-threshold type 1 cold sensitive or high-threshold type 2 cold sensitive. The hypothesis was tested, in intact and injured afferent nerve fibers, that low-threshold cold-sensitive afferent nerve fibers are activated by the transient receptor potential melastatin 8 (TRPM8) agonist menthol, whereas high-threshold cold-sensitive C-fibers and cold-insensitive afferent nerve fibers are menthol insensitive. In anesthetized rats, activity was recorded from afferent nerve fibers in strands isolated from the sural nerve, which was either intact or crushed 6–12 days before the experiment distal to the recording site. In all, 77 functionally identified afferent C-fibers (30 intact fibers, 47 injured fibers) and 34 functionally characterized A-fibers (11 intact fibers, 23 injured fibers) were tested for their responses to menthol applied to their receptive fields either in the skin (10 or 20%) or in the nerve (4 or 8 mM). Menthol activated all intact ( n = 12) and 90% of injured ( n = 20/22) type 1 cold-sensitive C-fibers; it activated no intact type 2 cold-sensitive C-fibers ( n = 7) and 1/11 injured type 2 cold-sensitive C-fibers. Neither intact nor injured heat- and/or mechanosensitive cold-insensitive C-fibers ( n = 25) and almost no A-fibers ( n = 2/34) were activated by menthol. These results strongly argue that cutaneous type 1 cold-sensitive afferent fibers are nonnociceptive cold fibers that use the TRPM8 transduction channel.


1981 ◽  
Vol 55 (2) ◽  
pp. 246-253 ◽  
Author(s):  
Harold P. Smith ◽  
Joe M. McWhorter ◽  
Venkata R. Challa

✓ Reports differ on which nerve fibers are affected by radiofrequency lesions made in peripheral nerves, some stating that primarily the myelinated delta and unmyelinated C fibers are destroyed, others stating that the destruction affects all sizes of nerve fibers and both myelinated and unmyelinated fibers. This study was designed to confirm one of those two findings, and to study the role that different temperatures might play in determining which fibers are affected. Radiofrequency lesions (85°C for 2 minutes) were made in dogs by placing a temperature-monitored electrode into the lumbar intervertebral foramina. The dogs were killed at intervals up to 6 weeks after rhizotomy, and the lesions were studied by light and electron microscopy. In all lesions, there was a total loss of unmyelinated fibers and a nearly total loss of myelinated fibers. In other dogs, 2-minute lesions were made at 45°, 55°, 65°, and 75°C, and the lesions examined 1 week later. Again, all sizes and all types of fibers were destroyed.


2020 ◽  
pp. S43-S54
Author(s):  
T. Pecova ◽  
I. Kocan ◽  
R. Vysehradsky ◽  
R. Pecova

Itch is the most common chief complaint in patients visiting dermatology clinics and is analogous to cough and also sneeze of the lower and upper respiratory tract, all three of which are host actions trying to clear noxious stimuli. The pathomechanisms of these symptoms are not completely determined. The itch can originate from a variety of etiologies. Itch originates following the activation of peripheral sensory nerve endings following damage or exposure to inflammatory mediators. More than one sensory nerve subtype is thought to subserve pruriceptive itch which includes both unmyelinated C-fibers and thinly myelinated Aδ nerve fibers. There are a lot of mediators capable of stimulating these afferent nerves leading to itch. Cough and itch pathways are mediated by small-diameter sensory fibers. These cough and itch sensory fibers release neuropeptides upon activation, which leads to inflammation of the nerves. The inflammation is involved in the development of chronic conditions of itch and cough. The aim of this review is to point out the role of sensory nerves in the pathogenesis of cough and itching. The common aspects of itch and cough could lead to new thoughts and perspectives in both fields.


Cephalalgia ◽  
1988 ◽  
Vol 8 (2) ◽  
pp. 83-91 ◽  
Author(s):  
Stephen Markowitz ◽  
Kiyoshi Saito ◽  
Michael A Moskowitz

C-fiber- dependent neurogenic plasma extravasation developed in the dura mater but not the brain after electric stimulation of the rat trigeminal ganglion or after chemical stimulation of perivascular axons with intravenous capsaicin, a drug that depolarizes sensory nerve fibers. C-fiber- independent extravasation also developed in this tissue after intravenous injections of substance P or neurokinin A (two constituents of unmyelinated C fibers) and after serotonin, bradykinin, or allergic challenge in presensitized animals. Intravenous dihydroergotamine or ergotamine tartrate, in doses similar to those used to treat migraine and cluster headache, prevented the stimulation-induced leakage of plasma proteins within the dura mater. Not unexpectedly, the acute administration of methysergide, a drug effective in the prophylactic treatment of headache, was inactive in this acute model. Neither acute nor chronic administration of propranolol affected stimulation-induced leakage of plasma protein. These results demonstrate that neurogenic inflammation develops within the dura mater in the rat and that ergot alkaloids prevent the process by a C-fiber-dependent mechanism.


2020 ◽  
Author(s):  
Ran Zhang ◽  
Xi Zhang ◽  
Yaping Chen ◽  
Weiqun Song

Abstract Background: Damage to sensory input is one of the pathologies underlying chronic ankle instability (CAI). Therefore, it is necessary to evaluate the sensory function of patients with CAI. This study aims to quantitatively evaluate sensory nerve function in patients with CAI and healthy controls using current perception threshold (CPT) measurements.Methods: Fifty-nine subjects with CAI and 30 healthy control individuals participated in this study. CPT values at the anterior talofibular ligament region were tested on the injured and uninjured sides in CAI patients and on a random side in the healthy control group.Results: There were no significant differences in age, gender, height, weight or BMI between the CAI and healthy control groups. The CPT values did not show significant gender differences. The CPT values were not significantly correlated with age or BMI. Compared to the control group (250 Hz: 24.32±9.28, 5 Hz: 6.87±1.56), the CAI group had significantly higher CPT values on the injured (250 Hz: 42.83±28.49, 5 Hz: 23.43±18.53) and uninjured sides (250 Hz: 38.62±19.98, 5 Hz: 18.84±14.21) under 250 Hz and 5 Hz electrical stimuli (p<0.01). No significant difference was observed under 2000 Hz stimuli. There were correlations among CPT values at different frequencies (p<0.01).Conclusion: This study revealed increased sensory thresholds in injured and uninjured ankles of 250 Hz- and 5 Hz-related sensory nerve fibers among patients with CAI. The bilateral change in sensory threshold may indicate a central sensory modulation process.Level of Evidence: Level III, case-control study.


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