Development of spontaneous activity and mechanosensitivity in axotomized afferent nerve fibers during the first hours after nerve transection in rats

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)

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.


1987 ◽  
Vol 57 (3) ◽  
pp. 702-711 ◽  
Author(s):  
T. Kumazawa ◽  
K. Mizumura ◽  
J. Sato

Characteristics of the polymodal receptor were studied using in vitro testis superior spermatic nerve preparations excised from anesthetized dogs. They were in most aspects similar to those reported previously using in vivo preparations. The majority (90%) of the tested polymodal units had small myelinated nerve fibers; the rest had nonmyelinated fibers. The mean mechanical threshold as determined by von Frey hairs was 17.5 g/mm2 (n = 476). There was a tendency for a unit with a higher conduction velocity to have a lower mechanical threshold. Bradykinin and hypertonic saline consistently caused a dose-dependent increase in discharge rate of these units; high K+ solution was also found to be a consistent stimulant. The responses of C-fiber receptors were not significantly different from those of A-delta-fibers. Heat stimulation up to 50 degrees C evoked discharges in 99 out of the total 103 units tested. The mean threshold temperature was 44.4 degrees C for the first trial. In 19 units in which the same heat stimulation was tested after an interval of 10 min, 10 units showed sensitization; 3 units were deactivated; and no clear difference was observed in the rest. No unit responded with a substantial increase in discharge rate to cold stimuli of 20 degrees C or less. A small temperature rise of 2 degrees C from the normal surface temperature of the testis (34 degrees C) significantly increased the response to hypertonic saline (616 mM) (2.41 +/- 0.22 impulses/s at 34 degrees C to 3.23 +/- 0.44 impulses/s at 36 degrees C) and to bradykinin (9 X 10(-8) M) (1.95 +/- 0.35 impulses/s at 34 degrees C to 2.85 +/- 0.19 impulses/s at 36 degrees C). The majority of the units recorded from the superior spermatic nerve in this experiment were most probably of polymodal receptor type, although the heat response was tested in a limited number of units. A very small number of a different type of receptor was discovered: rapidly adapting mechano-receptors, which responded almost exclusively to mechanical stimulation and were especially sensitive to a light mechanical stimulus moving across the receptive fields. The response properties of receptors studied in vitro remained practically unchanged during the experiments of several hours. The present experiments have shown that this preparation is suitable for systematic investigations, especially of the effects of chemical agents, on the polymodal receptor, which plays important roles in nociceptive functions.


2009 ◽  
Vol 101 (6) ◽  
pp. 3169-3191 ◽  
Author(s):  
Heinrich Neubauer ◽  
Christine Köppl ◽  
Peter Heil

In vertebrate auditory systems, the conversion from graded receptor potentials across the hair-cell membrane into stochastic spike trains of the auditory nerve (AN) fibers is performed by ribbon synapses. The statistics underlying this process constrain auditory coding but are not precisely known. Here, we examine the distributions of interspike intervals (ISIs) from spontaneous activity of AN fibers of the barn owl ( Tyto alba), a nocturnal avian predator whose auditory system is specialized for precise temporal coding. The spontaneous activity of AN fibers, with the exception of those showing preferred intervals, is commonly thought to result from excitatory events generated by a homogeneous Poisson point process, which lead to spikes unless the fiber is refractory. We show that the ISI distributions in the owl are better explained as resulting from the action of a brief refractory period (∼0.5 ms) on excitatory events generated by a homogeneous stochastic process where the distribution of interevent intervals is a mixture of an exponential and a gamma distribution with shape factor 2, both with the same scaling parameter. The same model was previously shown to apply to AN fibers in the cat. However, the mean proportions of exponentially versus gamma-distributed intervals in the mixture were different for cat and owl. Furthermore, those proportions were constant across fibers in the cat, whereas they covaried with mean spontaneous rate and with characteristic frequency in the owl. We hypothesize that in birds, unlike in mammals, more than one ribbon may provide excitation to most fibers, accounting for the different proportions, and that variation in the number of ribbons may underlie the variation in the proportions.


2009 ◽  
Vol 101 (6) ◽  
pp. 2762-2774 ◽  
Author(s):  
Lydia Grossmann ◽  
Natalia Gorodetskaya ◽  
Ralf Baron ◽  
Wilfrid Jänig

Afferent A- and C-fibers regenerating into a nerve following peripheral nerve injury are exposed to inflammatory mediators released by Schwann cells, resident and invading macrophages, and other inflammatory cells. Here we tested the hypothesis that ongoing and evoked activity in these afferent fibers are enhanced by a mixture of inflammatory mediators [inflammatory soup (IS)] applied to the injured nerve. Using in vivo electrophysiology, regenerating afferent nerve fibers were studied 7–14 days after sural nerve crush lesion. The ectopic activity was studied before and ≤1.5 h after topical application of IS to the nerve in 73 C-fibers and 22 A-fibers that were either ectopically active before application of IS (61 C-fibers, 17 A-fibers) or recruited by IS (12 C-fibers, 5 A-fibers). More than one half of the C-fibers were activated by IS for ≤90 min after its removal. The majority of mechano- (23/38) and heat-sensitive (29/35) C-fibers as well as mechano-sensitive A-fibers (12/17) decreased their activation thresholds and/or increased the response magnitude to mechanical and/or heat stimulation of the nerve. Noxious cold sensitivity, but not nonnoxious cold sensitivity, was weakly influenced by IS. Some initially nonresponsive C- and A-fibers developed new ectopic properties, i.e., were recruited, and exhibited ongoing activity and/or could be activated by physiological stimuli after application of IS. The results suggest that inflammatory mediators may be critical to enhance ectopic excitability of regenerating afferent nerve fibers. These peripheral mechanisms may be important triggering and maintaining neuropathic pain.


1995 ◽  
Vol 73 (3) ◽  
pp. 1270-1281 ◽  
Author(s):  
A. Lysakowski ◽  
L. B. Minor ◽  
C. Fernandez ◽  
J. M. Goldberg

1. Semicircular-canal afferents in the squirrel monkey were characterized by their resting discharge, discharge regularity, sensitivity to galvanic currents delivered to the ear (beta *), the gain (g2Hz), and phase lead (phi 2Hz) of their response to 2-Hz sinusoidal head rotations, and their antidromic conduction velocity. Discharge regularity was measured by a normalized coefficient of variation (CV*); the higher the CV*, the more irregular the discharge. g2Hz and phi 2Hz were expressed relative to angular head velocity. 2. These physiological measures were used in an attempt to discern the discharge properties of the three morphological classes of afferents innervating the crista. Presumed bouton (B) fibers were identified as slowly conducting afferents. Presumed calyx (C) fibers were recognized by their irregular discharge and low rotational gains. The remaining fibers were considered to be dimorphic (D) units. Single letters (B, C, and D) are used to emphasize that the classification is based on circumstantial evidence and may be wrong for individual fibers. Of the 125 identified fibers, 13 (10%) were B units, 36 (29%) were C units, and 76 (61%) were D units. 3. B units were regularly discharging D units ranged from regularly to irregularly discharging. C units were the most irregularly discharging afferents encountered. The mean resting discharge for the entire sample was 74 spikes/s. Resting rates were similar for regularly discharging B and D units and higher than those for irregularly discharging C and D units. 4. Except for their lower conduction velocities, the discharge properties of B units are indistinguishable from those of regularly discharging D units. Many of the discharge properties of B and D units vary with discharge regularity. There is a strong, positive relation when beta *, g2Hz, or phi 2Hz is plotted against CV*. For beta * or phi 2Hz, C units conform to the relation for B and D units. In contrast, values of g2Hz for C units are three to four times lower than predicted from the relation for the other two classes. 5. Internal (axon) diameters (dp) of peripheral vestibular-nerve fibers were estimated from central antidromic conduction velocities. Thick fibers (dp > or = 49 microns) were irregularly discharging, mostly C units. Medium-sized fibers (dp = 1.5-4 microns) included regular, intermediate, and irregular D units, as well as C units. Thin fibers (dp < or = 1.5 microns) were defined as B units.(ABSTRACT TRUNCATED AT 400 WORDS)


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.


1968 ◽  
Vol 46 (6) ◽  
pp. 887-896 ◽  
Author(s):  
Canio Polosa

Electrical activity of sympathetic preganglionic neurons in the upper thoracic cord of anesthetized cats was recorded with extracellular microelectrodes. The neurons were identified by their antidromic response to stimulation of the ipsilateral sympathetic cervical nerve. Of a total of 210 units observed, only 44 (21%) were spontaneously active. The discharge pattern was "regular" in 7%, "bursty" in 15%, and "irregular" in 78% of the units. The mean discharge rate was 1.4 spikes/s (range 0.1–5.6) and in any one cell changed little with time. Most spike trains showed a lack of short (i.e. less than 100 ms) interspike intervals. Interpolation of an antidromic impulse in the "regular" spike trains caused a resetting of the rhythm, thus suggesting that the rhythm is endogenous to the sympathetic preganglionic neuron itself. Spontaneous activity was observed in a decentralized, deafferented segment of spinal cord, thus suggesting that the activity can be autochthonous. Injection of a pressor drug resulted in a transient depression of the rate of spontaneous firing. Hemorrhage caused a transient increase of the rate of firing in some units, in others a transient decrease or complete arrest.


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 65 (6) ◽  
pp. 1580-1597 ◽  
Author(s):  
R. A. Eatock ◽  
T. F. Weiss ◽  
K. L. Otto

1. Rate-level functions for individual cochlear nerve fibers of the alligator lizard, Gerrhonotus multicarinatus, were generated by measuring a fiber's driven discharge rate (the difference between the average discharge rates in the presence and absence of a tone burst) as a function of sound pressure level. 2. When plotted in double logarithmic coordinates, the rate-level function approaches a straight line at low sound pressure levels and saturates at high levels. Thus the rate-level function is a saturating power function of sound pressure. We developed an algorithm to estimate the exponent of the straight-line portion of the function. When tested on simulated data with known parameters, the algorithm provided unbiased estimates of the exponent. 3. Nerve fibers innervating two distinct regions of the alligator lizard's auditory organ, the free-standing region and the tectorial region, have differing rate-level functions. 4. The mean exponent estimate of the rate-level functions of fibers innervating the free-standing region is approximately 2 at all frequencies. For stimulus frequencies at the characteristic frequency (CF), the mean value was 2.1 +/- 0.10 (SE, n = 131). For stimulus frequencies above and below CF, the mean exponent estimates were 2.1 +/- 0.13 (n = 49) and 2.1 +/- 0.11 (n = 34), respectively. A value of 2 is expected for a broad class of nonlinear systems. 5. The mean exponent estimates of the rate-level functions of fibers innervating the tectorial region were 3.0 +/- 0.30 (n = 32) for stimulus frequencies at CF, 2.5 +/- 0.33 (n = 3) for stimulus frequencies below CF, and 1.0 +/- 0.21 (n = 16) for stimulus frequencies above CF. Both the deviation from square-law behavior at CF and the frequency dependence of the exponent imply that nonlinear processing in the tectorial region differs intrinsically from that in the free-standing region. 6. For free-standing fibers, the saturation rate of the rate-level function (the maximum driven rate) is independent of stimulus frequency. This suggests that, in the free-standing region, 1) the alternating (AC) component of the receptor potential makes no significant contribution to the average rate of discharge and 2) neural saturation results from a process that occurs after the narrow-band frequency-selective process(es). 7. In tectorial fibers, the saturation rate is a bandpass function of sound frequency, with a broad peak between 150 and 300 Hz. This function appears to be common to all tectorial fibers.(ABSTRACT TRUNCATED AT 400 WORDS)


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.


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