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M Devor

Publications and source records attributed to M Devor.

At least 73 records · Page 4Linked to original sources
PubMed1988

Centrifugal activity in afferent C-fibers influences the spontaneous afferent barrage generated in nerve-end neuromas.

We have investigated the effect of a prolonged, low-frequency impulse barrage on the spontaneous afferent discharge that originates in experimental nerve-end neuromas in the rat sciatic nerve. Centrifugal activity in afferent A-fibers did not affect electrogenesis in the neuroma. When C-fibers were recruited, however, over half of the axons tested were either suppressed or excited. We suggest that these effects resulted from the stimulation-evoked release of neuroactive peptides or related substances from the cut ends of afferent C-fibers.

Afferent Pathways↗
PubMed1988

Abnormal impulse discharge in primary afferent axons injured in the peripheral versus the central nervous system.

Chronic injury to sensory axons in the rat peripheral nerve induces pathophysiologic changes in the axolemma at the cut nerve end, which are reflected in spontaneous ectopic impulse discharge and hyperexcitability to a range of depolarizing stimuli. We asked whether sensory axons injured in the central nervous system (CNS) also respond in this way. Primary afferent axons were severed in the sciatic nerve and, alternatively, in the midcervical or upper lumbar dorsal column (DC). Measurements of abnormal discharge from myelinated afferents showed high levels of spontaneous activity generated at the nerve injury site, especially during the period 3-16 days postoperatively, but comparatively little activity generated at the DC lesion site at any postoperative time. There was a corresponding difference in ectopic hyperexcitability to mechanical and adrenergic stimulation, and to depolarization with topical K+. DC lesion sites were not made more excitable by concurrent transection of the sciatic nerve, or by placing an autologous graft of excised sciatic nerve tissue into the DC defect at the time of initial surgery. Transection sites on dorsal roots L4 and L5 yielded abnormal discharge similar to that of sciatic nerve neuromas, indicating that the relative silence of DC transection sites was related to the CNS environment and not to position with respect to the sensory cell body.

Afferent Pathways↗
PubMed1988

End-structure of afferent axons injured in the peripheral and central nervous system.

The end-structure of afferent axons chronically severed in the rat sciatic nerve or dorsal column (DC) was visualized by centrifugal transport of horseradish peroxidase (HRP) or wheatgerm agglutinin conjugated to HRP (WGA:HRP) injected into the L4 or L5 dorsal root ganglion. Nerve regeneration was prevented and neuroma formation encouraged by tightly ligating the cut nerve end. For the first few weeks postoperative, the time during which afferents trapped in a nerve-end neuroma generate their most intense ectopic impulse barrage, the developing neuroma was dominated by swollen terminal end-bulbs. There was some axonal dying-back, retrograde fiber growth, and terminal sprouting, but little preterminal branching. The rich tangle of fine preterminal branches usually thought of in relation to nerve-end neuromas did not elaborate until several months postoperative, a time when the neuroma is relatively quiescent electrically. Afferents cut in the DC, which never develop dramatic ectopic electrical activity, showed morphological peculiarities similar to nerve-end neuromas during the early postoperative period, including retrograde fiber growth and minimal sprouting. They did not, however, go on to form luxuriant branches. These data provide preliminary clues as to the structure of the ectopic impulse-generating mechanism thought to underlie paresthesias and pain associated with peripheral nerve injury.

Afferent Pathways↗
PubMed1987

Afterdischarge and interactions among fibers in damaged peripheral nerve in the rat.

Sensory fibers trapped in nerve-end neuromas become abnormally excitable, and produce an ectopic discharge which is believed to contribute to paresthesias and pain associated with chronic nerve injury in man. Here we report that stimulation of injured nerves can alter this discharge, directly by antidromic invasion of active neuroma fibers, and indirectly through interactions with neighboring fibers. Antidromic stimulation of spontaneously active fibers in experimental neuromas in the rat sciatic nerve, using single electrical stimulus pulses, produced time-locking of rhythmic spontaneous firing and of spontaneous impulse bursts. Some initially silent fibers generated a burst of rhythmic afterdischarge when stimulated in this way. Stimulation delivered in brief trains (tetani) produced more prolonged alterations in spontaneous neuroma discharge, including excitation, suppression and combinations of the two. In some cases initially silent fibers were activated for extended periods. These responses to tetanic stimulation occurred even when the active fibers were not themselves stimulated, and reflect a novel form of fiber-fiber interaction in neuromas that we term 'crossed afterdischarge'. This interaction probably results from the accumulation of potassium ions within the extracellular compartment adjacent to active neuroma fibers during activation of their neighbors. It differs fundamentally from the high safety factor ephaptic cross-talk seen in acutely cut nerves and in neuromas of 30 or more days standing.

Action Potentials↗
PubMed1987

Extent of fiber regeneration after peripheral nerve repair: silicone splint vs. suture, gap repair vs. graft.

The degree of regeneration in surgically repaired sciatic nerves in rats was measured using a simple new electrophysiologic method: comparison of the size of nerve responses evoked by stimulation distal and proximal to the anastomosis. Five different repair procedures were evaluated. After simple end-to-end suture anastomosis, about 40% of the severed parent fibers regenerated past the suture line. The result was substantially improved when the anastomosis was covered with a newly designed thinwall silicone sheath which incorporated a narrow longitudinal slit. The presence of suture material at the point of anastomosis had no effect. Finally, regeneration across a 5-mm gap ensheathed in silicone (67%) was better than regeneration through a 5-mm autograft (45%).

Action Potentials↗
PubMed1987

Completeness and selectivity of ricin "suicide transport" lesions in rat dorsal root ganglia.

Ricinus communis agglutinin (MW 60 kDa type, RCA60, ricin) injected into the rat sciatic nerve produces massive degeneration of cells in those dorsal root ganglia (DRGs) known to contain the sensory cells-of-origin of the sciatic nerve. We have evaluated the extent of this cell death quantitatively. Using 1 or 2 micrograms RCA60, the average proportion of L5 DRG neurons destroyed closely matched the proportions of neurons in this ganglion known to have an axon in the sciatic nerve. A lower dose, 0.2 microgram ricin, produced substantially less cell death. There was heavy fiber degeneration in the sciatic nerve proximal to the injection site, but not in a nearby tributary nerve with which it shares the L5 DRG. Furthermore, the topographic distribution of Fink-Heimer argyrophilia corresponded to the known sciatic nerve distribution. The data suggest that at appropriate doses toxic ricin can produce a near complete and selective lesion by retrograde "suicide transport".

Animals↗
PubMed1986

Retrograde slowing of conduction in sensory axons central to a sciatic nerve neuroma.

We have plotted the time-course of retrograde slowing of impulse conduction velocity in myelinated afferent fibers after sciatic nerve transection and ligation, using compound action potential recordings, and samples of single afferent fibers. Conduction slowed rapidly during the first few weeks postoperative, and then the rate of slowing declined, approaching an asymptote after about 5 months. There was no indication of recovery. The initial decline in conduction velocity that follows nerve crush was similar to that following nerve transection. Upon regeneration, however, conduction velocity returned to near baseline values. Afferent fibers in the neighboring posterior biceps nerve share conduction pathways, dorsal root ganglia, and spinal terminal fields with sciatic nerve afferents, but their conduction velocity was not reduced following sciatic nerve injury.

Action Potentials↗
PubMed1985

Neurogenesis in adult rat dorsal root ganglia.

Nerve cells in mammalian species, including primary sensory neurons in the dorsal root ganglia (DRGs), are thought to be generated pre- or perinatally. The only known exceptions are olfactory receptor cells and some cortical microneurons. We now report results of experiments in which the number of neurons in the L4 and L5 DRGs of normal adult rats was counted from serial 10-micrometers paraffin sections stained with cresyl violet. Contrary to expectations, we found that there is a gradual increase in the number of DRG neurons as the animals age. The neuronal population nearly doubles over the adult life of the animal.

Age Factors↗
PubMed1985

Phenytoin suppresses spontaneous ectopic discharge in rat sciatic nerve neuromas.

Afferent fibers ending in nerve-end neuromas generate spontaneous impulse discharge which has been implicated as a cause of paraesthesias and pain following peripheral nerve injury in man. We now show in rats that the anticonvulsant drug phenytoin (PT), applied systemically or topically onto desheathed neuromas, suppresses the generation of neuroma discharge without blocking impulse conduction. The effect is dose-dependent and reversible upon drug washout. Since PT is known to provide effective pain relief in some kinds of neuralgia, the data suggest that the clinical analgesic action of PT in these conditions may, at least in part, involve a direct suppression of ectopic impulses generated in the region of the nerve damage.

Animals↗
PubMed1985

Proliferation of primary sensory neurons in adult rat dorsal root ganglion and the kinetics of retrograde cell loss after sciatic nerve section.

This study was aimed at measuring the kinetics of retrograde death among primary sensory neurons axotomized by transection of the ipsilateral sciatic nerve in adult rats. Using electrophysiological and retrograde transport methods, we first determined that most sciatic afferents enter the spinal cord along the L4 and L5 dorsal roots (DRs), and that about 54% of the cells in the L4 and L5 dorsal root ganglia (DRGs) project an axon into the sciatic nerve. Knowing this value, we could then calculate the rate of loss of axotomized neurons from the overall rate of neuron loss in the DRGs at different times after the lesion. Following unilateral sciatic neurectomy, we found a steady falloff in the ratio of DRG neurons on the operated versus the intact control sides in cresyl-violet-stained serial paraffin sections. We were surprised to note, however, that on the control side there was a steady increase in the cell count with age. Counts done on a series of unoperated rats of various ages confirmed this natural increase. Overall, new neurons accrete at an average rate of 18.1 cells per day to the combined L4 and L5 DRGs, nearly doubling their numbers during the adult life of the animal. The new cells add mostly to the small-diameter neuronal compartment. Evidence from neonatally operated rats indicates that the decline in the ratio of neurons in operated versus control DRGs following sciatic nerve section in the adult results more from a halt in the accretion of new neurons to the sciatic compartment than from frank cell death. From our data, we calculate that the loss of axotomized neurons occurs at a rate of only about 8% per 100 postoperative days.

Animals↗
PubMed1984

Intraneuronal substance P contributes to the severity of experimental arthritis.

There is evidence that substance P is a peptide neurotransmitter of some unmyelinated primary afferent nociceptors and that its release from the peripheral terminals of primary afferent fibers mediates neurogenic inflammation. The investigators examined whether substance P also contributes to the severity of adjuvant-induced arthritis, an inflammatory disease in rats. They found that, in the rat, joints that developed more severe arthritis (ankles) were more densely innervated by substance P-containing primary afferent neurons than were joints that developed less severe arthritis (knees). Infusion of substance P into the knee increased the severity of arthritis; injection of a substance P receptor antagonist did not. These results suggest a significant physiological difference between joints that develop mild and severe arthritis and indicate that release of intraneuronal substance P in joints contributes to the severity of the arthritis.

Animals↗
PubMed1984

Membrane differentiation in rat dorsal root ganglia and possible consequences for back pain.

The ferric ion-ferrocyanide staining procedure (Quick and Waxman, J. Neurol. Sci., 31 (1977) 1-11), believed to label selectively membrane regions with high sodium-channel content and hence elevated electrical excitability, was used to stain lower lumbar dorsal root ganglion (DRG) neurons in adult rats. In many such cells, including both large type A neurons and small type B neurons, the initial segment of the stem axon and a variable portion of the adjacent soma surface stained heavily. It is suggested that this membrane specialization represents a zone of elevated excitability which may contribute to ectopic impulse generation in DRGs.

Animals↗
PubMed1984

Dichotomizing somatic nerve fibers exist in rats but they are rare.

Electrophysiological methods that resolve problems of current spread were used to reinvestigate recent claims that over 40% of myelinated afferent neurons in rats have dichotomizing axons in which branches are maintained in two separate hindlimb nerves. Out of a sample of about 6400 axons recorded in rat hindlimb nerves including 3641 myelinated afferents, 14 axons were found to have a branch in both the sciatic nerve and a second somatic nerve. Examples were found of dichotomizing myelinated afferents, myelinated efferents and unmyelinated afferents.

Animals↗
PubMed1984

Effect of nerve section on the spinal distribution of neighboring nerves.

The spinal cord distribution of axonal terminals of peripheral nerves that innervate the skin of the upper medial thigh was examined in rats using transganglionic transport of horseradish peroxidase (HRP) and wheat-germ agglutinin-conjugated HRP (WGA-HRP). Chronic transection of the sciatic nerve or both the sciatic and saphenous nerves did not alter this distribution. Therefore, long-distance sprouting of intact 'thigh nerve' afferents in the dorsal horn is apparently not the mechanism whereby spinal dorsal horn neurons deafferented by sciatic and saphenous neurectomy, gain novel receptive fields in the cutaneous distribution of neighbouring intact nerves of the thigh.

Animals↗
PubMed1983

Potassium channels moderate ectopic excitability of nerve-end neuromas in rats.

The potassium conductance (gK) blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) strongly excited experimental neuromas that had spontaneous discharge, but had minimal effects on acutely cut nerves and on old, quiescent neuromas. Resting gK apparently moderates hyperexcitability in active neuromas.

4-Aminopyridine↗
PubMed1983

Sensory afferent impulses originate from dorsal root ganglia as well as from the periphery in normal and nerve injured rats.

Single units were recorded in dorsal roots or in the sciatic nerve of anaesthetised rats. It was shown by making sections, by stimulation and by collision that some ongoing nerve impulses were originating from the dorsal root ganglia and not from the central or peripheral ends of the axons. In a sample of 2731 intact or acutely sectioned myelinated sensory fibres, 4.75% +/- 3.7% contained impulses generated within the dorsal root ganglia. In 2555 axons sectioned in the periphery 2-109 days before, this percentage rose to 8.6% +/- 4.8%. There was a considerable variation between animals; 0-14% in intact and acutely sectioned nerves and 1-21% in chronically sectioned nerves. The conduction velocity of the active fibres did not differ significantly from the conduction velocity of unselected fibres. The common pattern of ongoing activity from the ganglion was irregular and with a low frequency (about 4 Hz) in contrast to the pattern of impulses originating in a neuroma which usually have a higher frequency with regular intervals. Slight mechanical pressure on the dorsal root ganglion increased the frequency of impulses. Unmyelinated fibres were also found to contain impulses originating in the dorsal root ganglion. In intact or acutely sectioned unmyelinated axons, the percentage of active fibres 4.4% +/- 3.5% was approximately the same as in myelinated fibres but there were no signs of an increase following chronic section. Fine filament dissection of dorsal roots and of peripheral nerves and collision experiments showed that impulses originating in dorsal root ganglia were propagated both orthodromically into the root and antidromically into the peripheral nerve. It was also shown that the same axon could contain two different alternating sites of origin of nerve impulses: one in the neuroma or sensory ending and one in the ganglion. These observations suggest that the dorsal root ganglion with its ongoing activity and mechanical sensitivity could be a source of pain producing impulses and could particularly contribute to pain in those conditions of peripheral nerve damage where pain persists after peripheral anaesthesia or where vertebral manipulation is painful.

Afferent Pathways↗
PubMed1983

Autotomy after nerve injury and its relation to spontaneous discharge originating in nerve-end neuromas.

Following transection and ligation of the sciatic and saphenous nerves, rodents frequently scratch and bite their anesthetic foot (autotomy). Many authors have suggested that autotomy is related to uncomfortable paresthesias induced by abnormal afferent discharge known to be generated in myelinated afferents in nerve-end neuromas. We report that preventing the development of ectopic neuroma discharge in rats by treating the severed nerves with colchicine or vinblastine does not prevent, or even detectably reduce, autotomy directed toward the denervated hindlimb. We conclude that abnormal discharge in myelinated afferents is not necessary for the expression of autotomy following nerve injury in rats.

Animals↗