Afferent sympathetic nerve fibres with aortic endings.
1. We recorded the electrical impulse activity of thirty-five single afferent fibres with aortic endings isolated from the third to the sixth left thoracic sympathetic rami communicantes of anaesthetized cats. The endings of each fibre were localized by mechanical probing of the opened aorta at the end of each experiment. 2. Twenty-four fibres had a single aortic receptive field. Eleven fibres had several and distinct receptive fields (from two to four): they were usually located in nearby aortic areas or, in addition, in other proximal portions of the arterial tree or in the adjacent pleura and connective tissue. 3. Twenty-nine fibres had conduction velocities ranging between 5 and 27 m/sec (Group Adelta), while six fibres had conduction velocities between 0-2 and 1-2m/sec (Group C). 4. The spontaneous impulse activity was in phase with the aortic pressure pulse and consisted of not more than one impulse per pressure pulse. It was increased during increases in aortic pressure and, conversely, decreased during decreases in aortic pressure. In vivo and post mortem studies showed that these mechanoreceptors had an impulse activity which rapidly adapted during sustained stimuli. They thus seem to signal pulsatile aortic stretch. 5. These aortic sympathetic afferents are likely to be part of a nervous pathway through which pressor reflexes, exhibiting positive feed-back characteristics, can elicited. (+info)
Modality-specific hyper-responsivity of regenerated cat cutaneous nociceptors.
1. Experiments were performed on anaesthetized cats to investigate the receptive properties of regenerated cutaneous tibial nerve nociceptors, and to obtain evidence for coupling between them and other afferent fibres as being possible peripheral mechanisms involved in neuropathic pain. These properties were studied 6-7 months after nerve section and repair. 2. Recordings were made from 25 regenerated nociceptors; 14 were A fibres and the remainder were C fibres. Their receptive field sizes and conduction velocities were similar to controls. There was no significant difference between their mechanical thresholds and those of a control population of nociceptors. 3. Regenerated nociceptors were significantly more responsive to suprathreshold mechanical stimuli than were uninjured control fibres. This increase in mechanical sensitivity occurred in both A and C fibres, although A fibres showed a greater increase in mechano-sensitivity than C fibres. Over half of the regenerated nociceptors (13/25) showed after-discharge to mechanical stimuli which was never seen in controls; the mean firing rate during this period of after-discharge was significantly related to both stimulus intensity and stimulus area. 4. There was no significant difference between the heat encoding properties of regenerated nociceptors and control nociceptors. Cold sensitivity was similarly unchanged. Thus, abnormal peripheral sprouting was unlikely to account for the increased mechanical sensitivity of the regenerated fibres. None of the regenerated nociceptors were found to be coupled to other fibres. 5. These results suggest that the clinical observation of mechanical hyperalgesia in patients after nerve injury may have a peripheral basis. Based on this model, other signs of neuropathic pain (i.e. tactile or thermal allodynia) are more likely to be due to altered central processing. (+info)
Sensory pathways in the spinal accessory nerve.
We obtained samples of spinal accessory nerve from patients undergoing radical surgery for tumours or nerve grafting in the neck. These were analysed by light and electron microscopy for the type of fibre. All contained fibres consistent with non-proprioceptive sensory function including pain. (+info)
Biomechanics of stretch-induced beading.
To account for the beading of myelinated fibers, and axons of unmyelinated nerve fibers as well of neurites of cultured dorsal root ganglia caused by mild stretching, a model is presented. In this model, membrane tension and hydrostatic pressure are the basic factors responsible for axonal constriction, which causes the movement of axonal fluid from the constricted regions into the adjoining axon, there giving rise to the beading expansions. Beading ranges from a mild undulation, with the smallest degree of stretch, to more globular expansions and narrow intervening constrictions as stretch is increased: the degree of constriction is physically limited by the compaction of the cytoskeleton within the axons. The model is a general one, encompassing the possibility that the membrane skeleton, composed mainly of spectrin and actin associated with the inner face of the axolemma, could be involved in bringing about the constrictions and beading. (+info)
Determinants of excitability at transition zones in Kv1.1-deficient myelinated nerves.
This study examines the role of K channel segregation and fiber geometry at transition zones of mammalian nerve terminals in the peripheral nervous system. Mutant mice that are deficient in Kv1.1, a fast Shaker K channel normally localized beneath the myelin sheath, display three types of cooling-induced abnormal hyperexcitability localized to regions before the transition zones of myelinated nerves. The first type is stimulus-evoked nerve backfiring that is absent at birth, peaks at postnatal day 17 (P17), and subsides in adults. The second type is spontaneous activity that has a more delayed onset, peaks at P30, and also disappears in older mice (>P60). TEA greatly amplifies this spontaneous activity with an effective dosage of approximately 0.7 mM, and can induce its reappearance in older mutant mice (>P100). These first two types of hyperexcitability occur only in homozygous mutants that are completely devoid of Kv1.1. The third type occurs in heterozygotes and represents a synergism between a TEA-sensitive channel and Kv1.1. Heterozygotes exposed to TEA display no overt phenotype until a single stimulation is given, which is then followed by an indefinite phase of repetitive discharge. Computer modeling suggests that the excitability of the transition zone near the nerve terminal has at least two major determinants: the preterminal internodal shortening and axonal slow K channels. We suggest that variations in fiber geometry create sites of inherent instability that is normally stabilized by a synergism between myelin-concealed Kv1.1 and a slow, TEA-sensitive K channel. (+info)
Human axons contain at least five types of voltage-dependent potassium channel.
1. We investigated voltage-gated potassium channels in human peripheral myelinated axons; apart from the I, S and F channels already described in amphibian and rat axons, we identified at least two other channel types. 2. The I channel activated between -70 and -40 mV, and inactivated very slowly (time constant 13.1 s at -40 mV). It had two gating modes: the dominant ('noisy') mode had a conductance of 30 pS (inward current, symmetrical 155 mM K+) and a deactivation time constant (tau) of 25 ms (-80 mV); it accounted for most ( approximately 50-75 %) of the macroscopic K+ current in large patches. The secondary ('flickery') gating mode had a conductance of 22 pS, and showed bi-exponential deactivation (tau = 16 and 102 ms -80 11 mV); it contributed part of the slow macroscopic K+ current. 3. The I channel current was blocked by 1 microM alpha-dendrotoxin (DTX); we also observed two other DTX-sensitive K+ channel types (40 pS and 25 pS). The S and F channels were not blocked by 1 microM DTX. 4. The conductance of the S channel was 7-10 pS, and it activated at slightly more negative potentials than the I channel; its deactivation was slow (tau = 41.7 ms at -100 mV). It contributed a second component of the slow macroscopic K+ current. 5. The F channel had a conductance of 50 pS; it activated at potentials between -40 and +40 V, deactivated very rapidly (tau = 1.4 ms at -100 mV), and inactivated rapidly (tau = 62 ms at +80 mV). It accounted for the fast-deactivating macroscopic K+ current and partly for fast K+ current inactivation. 6. We conclude that human and rat axonal K+ channels are closely similar, but that the correspondence between K+ channel types and the macroscopic currents usually attributed to them is only partial. At least five channel types exist, and their characteristics overlap to a considerable extent. (+info)
Distal axonopathy in peripheral nerves of PMP22-mutant mice.
A partial duplication of chromosome 17 is associated with Charcot-Marie-Tooth disease type 1A (CMT1A), a demyelinating peripheral neuropathy that causes progressive distal muscle atrophy and sensory impairment. Trisomic expression of peripheral myelin protein 22 (PMP22) whose gene is contained within the duplicated region is considered to be responsible for the disease. By using recombinant gene technology in rodents, we had demonstrated previously that PMP22 is sensitive to gene dosage. Homozygous PMP22 knockout (PMP22(0/0)) mice and transgenic animals carrying additional copies of the PMP22 gene develop distinct peripheral polyneuropathies. We have now performed a detailed morphometrical analysis of the L3 roots, quadriceps and saphenous nerves of these PMP22-mutant mice to study whether the myelin and potential axonal deficits are evenly distributed. The L3 roots and the peripheral nerves were chosen as representatives of the proximal and distal segments of the peripheral nervous system. When the roots were compared with the peripheral nerves, myelin deficiencies appeared more severe at the radicular levels, in particular the ventral roots. Decreased numbers of large calibre axons were a prominent feature in the motor branches of both strains of PMP22-mutant mice, and these axonal deficits were more severe distally. Active axonal damage was only observed in the nerves of PMP22(0/0) mice. Despite the distinct effects on myelination and the Schwann cell phenotype that characterize the neuropathies of PMP22-mutant mice, both strains develop a distally accentuated axonopathy as a common disease mechanism which is likely to be responsible for the neurological deficits. (+info)
Fibre composition in the interosseous nerve of the pigeon.
The interosseous nerve of birds innervates a string of Herbst corpuscles located near the interosseous membrane between the tibia and fibula. Fibre composition of this nerve was assessed including both myelinated and unmyelinated axons. The diameter of the whole nerve is approximately 100 microm. Complete data were obtained for 3 nerves. The mean total number of myelinated fibres and unmyelinated axons was 2872 +/- 53. The mean number of myelinated fibres was 280 +/- 20 and that for unmyelinated axons was 2600 +/- 47. There was a broad distribution of diameters for myelinated fibres ranging from approximately 2 microm to 10 microm with a distinct peak at approximately 3-5 microm and a less prominent second peak at 6-8 microm. Similarly, myelin sheath thickness distribution showed 2 peaks, one at 0.6-0.8 microm and another at 1.4-1.6 microm. It is suggested that the group represented by the second peak innervates the Herbst corpuscles. The group of smaller myelinated fibres and the unmyelinated axons are assumed to innervate other types of receptors, some of which may be nociceptors. (+info)