Axonal cross-excitation in nerve-end neuromas: comparison of A- and C-fibers.

1. We recorded from single afferent axons ending in chronic sciatic nerve end neuromas in rats with the use of the teased-fiber method. Axons were sought that had ongoing impulse discharge originating in the neuroma. 2. Recording from myelinated (A-) fibers, tetanic stimulation of neighboring axons (50 Hz, 5 or 10 s, intensity adequate to drive A-fibers) caused an increase, and sometimes a decrease, in the rate of ongoing discharge in 68% of the fibers tested. In addition, some initially silent neuroma A-fibers (1.4%) were activated in this way. Both A beta and A delta fibers responded, although the likelihood of response was greater in A beta fibers. We call this form of interfiber cross-excitation "crossed afterdischarge." 3. In contrast to A-fibers, crossed afterdischarge was evoked with these stimulation parameters in < or = 5% of the spontaneously active unmyelinated (C-) fibers sampled. No initially silent C-fibers were activated. 4. C-fibers remained largely insensitive to cross-excitation by neighboring axons even when the strength of stimulus pulses was increased so as to include neighboring A + C-fibers. 5. The difference between A- and C-fibers could not be accounted for on the basis of the maturity of the neuroma, rate and pattern of ongoing discharge, or use of Flaxedil paralysis. 6. The difference between A- and C-fibers is discussed in terms of two alternative mechanisms that may underlie crossed afterdischarge: mediation by a neurotransmitter(s) in a nonsynaptic mode, and mutual K+ depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechano- and thermosensitivity of injured muscle afferents

Injury of limb nerves leading to neuropathic pain mostly affects deep somatic nerves including muscle nerves. Here, we investigated the functional properties of injured afferent fibers innervating the lateral gastrocnemius-soleus muscle 4-13 h [time period (TP) I] and 4-7 days (TP II) after nerve crush in anesthetized rats using neurophysiological recordings from either the sciatic nerve (165 A-, 137 C-fibers) or the dorsal root L(5) (43 A-, 28 C-fibers). Ongoing activity and responses to mechanical or thermal stimulation of the injury site of the nerve were studied quantitatively. Of the electrically identified A- and C-fibers, 5 and 38% exhibited ectopic activity, respectively, in TP I and 51 and 61%, respectively, in TP II. Thus all afferent fibers in an injured muscle nerve developed ectopic activity since ～ 50% of the fibers in a muscle nerve are somatomotor or sympathetic postganglionic. Ongoing activity was present in 50% of the afferent A-fibers (TP II) and in 53-56% of the afferent C-fibers (TP I and II). In TP II, mechanical, cold, and heat sensitivity were present in 91, 63, and 52% of the afferent A-fibers and in 50, 40, and 66% of the afferent C-fibers. The cold and heat activation thresholds were 5-27 and 35-48°C, respectively, covering the noxious and innocuous range. Most afferent fibers showed combinations of these sensitivities. Mechano- and cold sensitivity had a significantly higher representation in A- than in C-fibers, but heat sensitivity had a significantly higher representation in C- than in A-fibers. These functional differences between A- and C-fibers applied to large- as well as small-diameter A-fibers. Comparing the functional properties of injured muscle A- and C-afferents with those of injured cutaneous A- and C-afferents shows that both populations of injured afferent neurons behave differently in several aspects.     

Toxic effects of triethyldodecylammoniumbromide (TEA-C12) on myelinated nerve fibers and blood-nerve barrier in the mouse

Summary The blocking effect of triethyldodecylammoniumbromide (TEA-C₁₂), applied locally to the sciatic nerve, was studied in 28 adult BDF₁ mice. Clinical parameters, electrophysiological recordings of muscle action potentials evoked by stimulation at the sciatic notch, and morphological aspects are presented. Our results show that both the minimal blocking concentration and half the minimal blocking concentration induce flaccid paresis of the treated hind-limb. There was a complete, long-lasting nerve conduction block due to Wallerian degeneration of the myelinated nerve fibers. In contrast, pain sensation was abolished only on day 4 after application of the minimal blocking concentration, but was preserved during the rest of the time that nerve conduction block was observed. This corresponded to the electron microscopic finding of preservation of unmyelinated nerve fibers. Recovery of nerve conduction was characterized electrophysiologically by occurrence of minute polyphasic regeneration potentials between day 18 and 21, clinically by advanced restitution of muscle force on day 64, and morphologically by nerve regeneration. TEA-C₁₂ also induced a disturbance of the blood-nerve barrier, demonstrated using an intraperitoneally administered biotinylated IgG tracer in the endoneurial space. The morphological features of the acute axonal changes of the myelinated nerve fibers including the degeneration of the axonal mitochondria suggest that the neurotoxic effect of TEA-C₁₂ is possibly mediated by interference with the axonal energy supply. The selective affection of myelinated nerve fibers separates TEA-C₁₂ from other neurotoxins that induce changes of the axonal microorganelles or complete Wallerian degeneration of myelinated and unmyelinated nerve fibers. The selectivity for myelinated nerve fibers and the supposed pathogenetic mechanism exhibit some similarities with the human polyneuropathy caused by acute arsenic acid intoxication.     

Characteristics of A- and C-fibers ending in a sensory nerve neuroma in the rat

1. We have studied, in vivo, the degree of spontaneous activity, responsiveness to mechanical and chemical stimuli, and the conduction velocities in C- and A-fibers ending in the neuromas formed 8-66 days after ligation and transection of a cutaneous sensory nerve in the rat. 2. Some of these C- and A-fibers developed ongoing activity. The percentage varied considerably between neuromas in different animals, from 0 to 23% (mean, 4.2%), with no major variation in the incidence as a function of neuroma age. 3. The endings of the fibers in the neuroma could be excited by both mechanical and chemical stimuli. From 0 to 26% (mean, 13%) of these fibers had mechanosensitive endings, some of which were located in the muscle/facia tissue outside the neuroma itself. Some fibers were excited by direct application of chemicals to their endings in the neuroma; 3.0% of A- and C-fibers responded to bradykinin, 2.0% to histamine, and 2.8% to adrenaline. There was no systemic variation in the percentages of mechano- or chemosensitive fibers with neuroma age. 4. The C-fiber action potentials showed a continuing decrease in conduction velocities over the 9 wk after nerve transection. More than 4 wk after transection, the conduction velocity of neuroma fibers was 88% that of C-fibers of normal saphenous nerve. 5. We conclude that fibers in a cutaneous nerve neuroma have some sensory capabilities similar to those in normal nerves terminating in the skin. This could be because they are retained after the nerve is transected or because they are initially lost but then regenerate. However, the numbers are restricted, probably because the fibers remain isolated from factors produced by their target skin tissue that are necessary for development and maintenance of sensory functions.     

Mechano- and thermosensitivity of regenerating cutaneous afferent nerve fibers

Crush lesion of a skin nerve is followed by sprouting of myelinated (A) and unmyelinated (C) afferent fibers into the distal nerve stump. Here, we investigate quantitatively both ongoing activity and activity evoked by mechanical or thermal stimulation of the nerve in 43 A- and 135 C-fibers after crush lesion of the sural nerve using neurophysiological recordings in anesthetized rats. The discharge patterns in the injured afferent nerve fibers and in intact (control) afferent nerve fibers were compared. (1) Almost all (98%) A-fibers were mechanosensitive, some of them exhibited additionally weak cold/heat sensitivity; 7% had ongoing activity. (2) Three patterns of physiologically evoked activity were present in the lesioned C-fibers: (a) C-fibers with type 1 cold sensitivity (low cold threshold, inhibition on heating, high level of ongoing and cold-evoked activity; 23%): almost all of them were mechanoinsensitive and 40% of them were additionally heat-sensitive; (b) C-fibers with type 2 cold sensitivity (high cold threshold, low level of ongoing and cold-evoked activity; 23%). All of them were excited by mechanical and/or heat stimuli; (c) cold-insensitive C-fibers (54%), which were heat- and/or mechanosensitive. (3) The proportions of C-fibers exhibiting these three patterns of discharge to physiological stimuli were almost identical in the population of injured C-fibers and in a population of 91 intact cutaneous C-fibers. 4. Ongoing activity was present in 56% of the lesioned C-fibers. Incidence and rate of ongoing activity were the same in the populations of lesioned and intact type 1 cold-sensitive C-fibers. The incidence (but not rate) of ongoing activity was significantly higher in lesioned type 2 cold-sensitive and cold insensitive C-fibers than in the corresponding populations of intact C-fibers (42/93 fibers vs. 11/72 fibers).     

Selective activation of C-fibers

Summary A polarizing current applied transiently to a nerve selectively blocks conduction in the A-fibers, whereas the C-fibers remain unaffected. The block is reversible. Stimulation of A-fibers by the polarizing current is prevented by appropriately adjusting its slope of rise.This work was supported by the Deutsche Forschungsgemeinschaft.     

Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys.

1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.     

电刺激隐神经不同纤维诱发丘脑束旁核电反应的研究

目的和方法：实验用不同强度刺激隐神经,配合极化电流阻断技术分别引起Ａ类纤维（Ａｆ）和Ｃ类纤维（Ｃｆ）传入丘脑束旁核的诱发电位,观察静脉注射吗啡（０．５ｍｇ／ｋｇ）对Ａ－ＰｆＥＰ和Ｃ－ＰｆＥＰ的影响。结果：Ａ类纤维和Ｃ类纤维均可传入丘脑束旁核引起诱发电位,但两者潜伏期和幅值有明显差异。静脉注射吗啡,可使Ｃ－ＰｆＥＰ幅值明显衰减,潜伏期延长;而Ａ－ＰｆＥＰ的幅值衰减不显著,潜伏期不延长。结论：Ｃ－Ｐｆ     

Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats

Both myelinated and unmyelinated afferents are implicated in transmitting diabetic neuropathic pain. Although unmyelinated afferents are generally considered to play a significant role in diabetic neuropathic pain, pathological changes in diabetic neuropathy occur mostly in myelinated A-fibers. In the present study, we first examined the role of capsaicin-sensitive C-fibers in the development of allodynia induced by diabetic neuropathy. We then studied the functional changes of afferent nerves pertinent to diabetic neuropathic pain. Diabetes was induced in rats by i.p. streptozotocin. To deplete capsaicin-sensitive C-fibers, rats were treated with i.p. resiniferatoxin (300 microg/kg). Mechanical and thermal sensitivities were measured using von Frey filaments and a radiant heat stimulus. Single-unit activity of afferents was recorded from the tibial nerve. Tactile allodynia, but not thermal hyperalgesia, developed in diabetic rats. Resiniferatoxin treatment did not alter significantly the degree and time course of allodynia. Post-treatment with resiniferatoxin also failed to attenuate allodynia in diabetic rats. The electrophysiological recordings revealed ectopic discharges and a higher spontaneous activity mainly in Adelta- and Abeta-fiber afferents in diabetic rats regardless of resiniferatoxin treatment. Furthermore, these afferent fibers had a lower threshold for activation and augmented responses to mechanical stimuli. Thus, our study suggests that capsaicin-sensitive C-fiber afferents are not required in the development of allodynia in this rat model of diabetes. Our electrophysiological data provide substantial new evidence that the abnormal sensory input from Adelta- and Abeta-fiber afferents may play an important role in diabetic neuropathic pain.     

Collateral sprouting of nociceptive C-fibers after cut or capsaicin treatment of the sciatic nerve in adult rats

The innervation area of nociceptive C-fibers in the saphenous nerve of adult rats was detected by the Evans blue technique, in which antidromic excitation of the nociceptive C-fibers causes a visible extravasation of dye in the skin it supplied. One month after cutting the sciatic nerve, the nociceptive C-fibers of the intact saphenous nerve had sprouted to the sciatic area. When capsaicin was locally applied to the nerve trunk to destroy C-fibers of the sciatic nerve, there was no sprouting of nociceptive C-fibers from the saphenous nerve. Thus, myelinated fibers and/or the functionally impaired C-fibers of the sciatic nerve are enough to prevent collateral sprouting of nociceptive C-fibers from the saphenous nerve.     

Physiology and morphology of multireceptive neurons with C-afferent fiber inputs in the deep dorsal horn of the rat lumbar spinal cord

Intracellular recording techniques have been used to study neurons that respond to low- and to high-intensity mechanical stimulation of the skin of the hindpaw (wide dynamic range or multireceptive cells) in the deep dorsal horn of the fourth lumbar segment of the spinal cord, in decerebrate-spinal rats. Electrical stimulation of the A-fibers in the sciatic nerve produced a short-latency response in all 32 neurons studied. A long-latency prolonged excitation was produced in 28 of the 32 neurons when the unmyelinated afferents in the sciatic nerve were activated. This paper describes the physiological properties of 12 multireceptive cells with A- and C-fiber inputs, whose cell body location was established by horseradish peroxidase ionophoresis and the morphology of six neurons in this group whose cell bodies lay within lamina V. Single stimuli to the sciatic nerve at an intensity high enough to activate unmyelinated afferent fibers (C-fiber strength) produced two patterns of response in the neurons. In five neurons a number of long-latency postsynaptic potentials (PSPs) clearly separated from the short-latency A-fiber evoked PSPs were produced, resulting in an early discharge, a silent period, and a late discharge. The second pattern, found in seven neurons, was a long-lasting depolarization, only generated by C-strength stimuli, which continued from the early A-fiber evoked PSPs, peaked at 100-200 ms, and lasted for 300-500 ms, producing in six cases a continuous burst of action potentials with a maximal frequency at the expected latency of the C-afferent fiber input but with no clear A- and C-fiber evoked banding of the action potentials. This postsynaptic depolarization was large enough to inactivate action potentials in one cell. Repeated stimuli to the sciatic nerve (1 Hz for 10 s) at C-fiber strength produced five different types of response in the neurons. In three neurons a progressive increase in the size and duration of the C-fiber PSPs occurred, resulting in an increase in the number of action potentials (windup), whereas in two, the repeated stimulation resulted in a progressive moderate depolarization of the neurons and an increase in the total number of action potentials evoked at both early and late latencies. Large depolarizations, sufficient to partially inactivate action potentials, developed during the repeated stimulation in two cells, effectively reducing the number of spikes evoked per stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Persisting selective block of unmyelinated fibers in cutaneous nerves of the cat by distilled water

Experiments were done in vivo on the sural nerve of the cat's hindlimb. The nerve was desheathed for a length of 8 mm and superfused by Tyrode solution or distilled water. Electrical stimulation and recording was used to evaluate conduction block of nerve fibers. Irrigation with distilled water for periods of 3-5 min caused a persisting selective block of conduction in C-fibers while most of the A-fibers were unaffected. Recovery of the C-fibers never occurred during the time of observation (up to 130 min).     

Comparison between electrophysiologic and morphologic changes in lead induced peripheral neuropathy in rats

Compound nerve action potential (CNAP) of the mixed peripheral nerve is composed of A alpha beta, A delta, and C potentials. All components of CNAPs in the sciatic nerve were recorded by stimulating the tibial nerve of both control and lead-poisoned rats. Marked decrease of nerve conduction velocity and prolonged duration were found in A alpha beta and A delta fibers especially in large myelinated A alpha beta fibers. The amplitude decreased in A alpha beta potential, but the area did not change. In C potential produced by activation of unmyelinated fibers, nerve conduction velocity slightly decreased, but the amplitude and area did not significantly change. Pathologic correlates revealed prominent segmental demyelination with significant decrease of large myelinated fiber densities. Minimal axonal degeneration of unmyelinated fibers was present. We can conclude that electrophysiologic changes in the lead-poisoned rats correlate with pathologic changes in them.     

Localization of TRPV1 and P2X3 in unmyelinated and myelinated vagal afferents in the rat

The vagus nerve is dominated by afferent fibers that convey sensory information from the viscera to the brain. Most vagal afferents are unmyelinated, slow-conducting C-fibers, while a smaller portion are myelinated, fast-conducting A-fibers. Vagal afferents terminate in the nucleus tractus solitarius (NTS) in the dorsal brainstem and regulate autonomic and respiratory reflexes, as well as ascending pathways throughout the brain. Vagal afferents form glutamatergic excitatory synapses with postsynaptic NTS neurons that are modulated by a variety of channels. The organization of vagal afferents with regard to fiber type and channels is not well understood. In the present study, we used tract tracing methods to identify distinct populations of vagal afferents to determine if key channels are selectively localized to specific groups of afferent fibers. Vagal afferents were labeled with isolectin B4 (IB4) or cholera toxin B (CTb) to detect unmyelinated and myelinated afferents, respectively. We find that TRPV1 channels are preferentially found in unmyelinated vagal afferents identified with IB4, with almost half of all IB4 fibers showing co-localization with TRPV1. These results agree with prior electrophysiological findings. In contrast, we found that the ATP-sensitive channel P2X3 is found in a subset of both myelinated and unmyelinated vagal afferent fibers. Specifically, 18% of IB4 and 23% of CTb afferents contained P2X3. The majority of CTb-ir vagal afferents contained neither channel. Since neither channel was found in all vagal afferents, there are likely further degrees of heterogeneity in the modulation of vagal afferent sensory input to the NTS beyond fiber type.     

大鼠坐骨神经超微结构的老年性变化

为了研究老年大鼠坐骨神经超微结构特点,随机取3月龄(成年组)和24月(老年组)龄正常SD大鼠各10只,用电镜观察两组间坐骨神经超微结构的差异。结果显示:老年组大鼠坐骨神经内有髓纤维的百分比、轴突间胶原纤维密度以及Schwann细胞胞质中脂褐质沉积密度均多于成年组(P<0.05);但无髓纤维之百分比少于成年组(P<0.05)。上述结果提示坐骨神经内的有髓纤维与无髓纤维百分比、轴突间胶原纤维密度以及Schwann细胞胞质中脂褐质沉积密度是衡量大鼠坐骨神经老化的形态标志之一。     

Neurotrophic modulation of myelinated cutaneous innervation and mechanical sensory loss in diabetic mice

Human diabetic patients often lose touch and vibratory sensations, but to date, most studies on diabetes-induced sensory nerve degeneration have focused on epidermal C-fibers. Here, we explored the effects of diabetes on cutaneous myelinated fibers in relation to the behavioral responses to tactile stimuli from diabetic mice. Weekly behavioral testing began prior to streptozotocin (STZ) administration and continued until 8 weeks, at which time myelinated fiber innervation was examined in the footpad by immunohistochemistry using antiserum to neurofilament heavy chain (NF-H) and myelin basic protein (MBP). Diabetic mice developed reduced behavioral responses to non-noxious (monofilaments) and noxious (pinprick) stimuli. In addition, diabetic mice displayed a 50% reduction in NF-H-positive myelinated innervation of the dermal footpad compared with non-diabetic mice. To test whether two neurotrophins nerve growth factor (NGF) and/or neurotrophin-3 (NT-3) known to support myelinated cutaneous fibers could influence myelinated innervation, diabetic mice were treated intrathecally for 2 weeks with NGF, NT-3, NGF and NT-3. Neurotrophin-treated mice were then compared with diabetic mice treated with insulin for 2 weeks. NGF and insulin treatment both increased paw withdrawal to mechanical stimulation in diabetic mice, whereas NT-3 or a combination of NGF and NT-3 failed to alter paw withdrawal responses. Surprisingly, all treatments significantly increased myelinated innervation compared with control-treated diabetic mice, demonstrating that myelinated cutaneous fibers damaged by hyperglycemia respond to intrathecal administration of neurotrophins. Moreover, NT-3 treatment increased epidermal Merkel cell numbers associated with nerve fibers, consistent with increased numbers of NT-3-responsive slowly adapting A-fibers. These studies suggest that myelinated fiber loss may contribute as significantly as unmyelinated epidermal loss in diabetic neuropathy, and the contradiction between neurotrophin-induced increases in dermal innervation and behavior emphasizes the need for multiple approaches to accurately assess sensory improvements in diabetic neuropathy.     

Increased number of unmyelinated fibers in the ventral root after peripheral neurectomy in adult rat

We examined the possibility that peripheral nerve injury in the adult rat triggers sprouting of unmyelinated ventral root afferent fibers. Three to 5 months after the sciatic nerve was sectioned on one side in the adult rat, myelinated and unmyelinated fibers were counted at 3 sites along the length of the ventral root. A sciatic nerve lesion resulted in about a 3-fold increase in the number of unmyelinated fibers in the L5 ventral root. Our data suggest that a peripheral nerve lesion in the adult rat triggers sprouting of unmyelinated afferent fibers in the ventral root. No evidence was found that dorsal rhizotomy triggers sprouting of afferent fibers.     

Peripheral coding of tonic mechanical cutaneous pain: comparison of nociceptor activity in rat and human psychophysics

These experiments investigated temporal summation mechanisms of tonic cutaneous mechanical pain. Human volunteers provided psychophysical estimates of pain intensity, which were compared with discharge patterns of rat cutaneous nociceptors tested with identical stimulus protocols. Human subjects made either intermittent or continuous ratings of pain intensity during stimulation of the skin between the thumb and first finger. Stimulus intensities of 25, 50, and 100 g were applied with a probe of contact area of 0.1 mm(2) for 2 min. Pain perception significantly increased during stimulation (temporal summation) for the 50- and 100-g stimulus intensities. Sequential conduction block of the myelinated fibers supplying the stimulated skin was used to investigate the role of A-fiber mechanoreceptors and nociceptors in this temporal summation. Conduction block of the Abeta fibers resulted in an increase in mechanically evoked pain estimates and an increase in temporal summation, consistent with loss of Abeta-mediated inhibition. When only conduction in the unmyelinated fibers remained, pain estimates were reduced to the preblock levels, but temporal summation was still present. Electrophysiological recordings were made from filaments of the sciatic nerve supplying receptors in the plantar skin of barbiturate-anesthetized rats. Forty units fulfilled the identification criteria for nociceptors: 20 A-fiber and 20 C-fiber nociceptors. Each unit was characterized by recording its responses to graded mechanical and heat stimuli. Nociceptors were also tested with stimuli identical to those applied to the human subjects. The responses of all units to sustained mechanical stimuli were adaptive-that is, they exhibited a gradual decline in response with time. However, the time course of adaptation varied among units. All the C-fiber nociceptors and one-half of the A-fiber nociceptors had rapidly adapting responses. The remainder of the A-fibers displayed slowly adapting responses. One-third of all units also showed short-duration increases in firing rate during stimulation. The latency after stimulus onset of this rate acceleration was inversely related to stimulus intensity. Despite the apparent disparity between perceptual temporal summation and nociceptor adaptation, central and peripheral mechanisms are proposed that can reconcile the relationship between nociceptor activity and pain perception.     

The Carotid Sinus Nerve—Structure,Function, and Clinical Implications

Interest has been renewed in the anatomy and physiology of the carotid sinus nerve (CSN) and its targets (carotid sinus and carotid body, CB), due to recent proposals of surgical procedures for a series of common pathologies, such as carotid sinus syndrome, hypertension, heart failure, and insulin resistance. The CSN originates from the glossopharyngeal nerve soon after its appearance from the jugular foramen. It shows frequent communications with the sympathetic trunk (usually at the level of the superior cervical ganglion) and the vagal nerve (main trunk, pharyngeal branches, or superior laryngeal nerve). It courses on the anterior aspect of the internal carotid artery to reach the carotid sinus, CB, and/or intercarotid plexus. In the carotid sinus, type I (dynamic) carotid baroreceptors have larger myelinated A-fibers; type II (tonic) baroreceptors show smaller A- and unmyelinated C-fibers. In the CB, afferent fibers are mainly stimulated by acetylcholine and ATP, released by type I cells. The neurons are located in the petrosal ganglion, and centripetal fibers project on to the solitary tract nucleus: chemosensory inputs to the commissural subnucleus, and baroreceptor inputs to the commissural, medial, dorsomedial, and dorsolateral subnuclei. The baroreceptor component of the CSN elicits sympatho-inhibition and the chemoreceptor component stimulates sympatho-activation. Thus, in refractory hypertension and heart failure (characterized by increased sympathetic activity), baroreceptor electrical stimulation, and CB removal have been proposed. Instead, denervation of the carotid sinus has been proposed for the “carotid sinus syndrome.” Anat Rec, 302:575–587, 2019. © 2018 Wiley Periodicals, Inc.     

Speed and temperature dependences of mechanotransduction in afferent fibers recorded from the mouse saphenous nerve

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 less, similar100 ms, even with very fast ramp stimuli (2,945 microm/s). We examined stimulus response functions and mechanical latency at two different temperatures (24 and 32 degrees 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 Q(10) values for mechanical latency in C-fibers to be 5.1; in contrast, the Q(10) 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.