The intensive aspect of information processing in the intradental A-delta system in man--a psychophysiological analysis of sharp dental pain.

The tooth pulp has many attractive features for the study of peripheral pain mechanisms because of its rich innervation, its unique distribution of nerve fibers and its general disposition to give rise to pain upon stimulation. An experimental model has been developed for simultaneous recordings of intradental multi-unit A-delta nerve activity and the subjective intensity and quality of pain evoked by tooth pulp stimulation in conscious, alert humans. The only teeth to be considered for this kind of investigations are those having such a periodontal condition that they have to be extracted. The nerve activity was recorded from two electrodes placed in the dentin on the labial tooth surface, one at the level of the most incisal part of the pulp, and the other as far apically as possible. Brief cold stimulation was produced by using evaporating ethyl chloride administered between the recording electrodes. The magnitude of perceived pain was estimated by means of an intermodal matching technique (finger span) in combination with verbal descriptors. Of three response criteria selected--average response amplitude, peak amplitude and area under the response curve (integral)--for describing the relationship between intradental nerve activity and sharp, shooting pain, the integral yielded the highest mean correlation coefficient.

Peripheral neuropathy in myotonic dystrophy: a nerve biopsy study.

Sural nerve biopsies from 13 unselected myotonic dystrophy patients and 6 normal controls were studied morphometrically. The myelinated fiber density was reduced in 11 of the 13 myotonic dystrophy patients, with preferential loss of large myelinated fibers. Unmyelinated fiber densities and diameters were normal. Teased fiber studies commonly revealed focal areas of remyelination and abnormal wrinkling of the myelin sheath. Measurement of internodal length disclosed features of both axonal regeneration and focal demyelination-remyelination. These findings are consistent with a chronic axonopathy of moderate severity, possibly due to axonal atrophy.

Is laser nerve repair comparable to microsuture coaptation?

Efforts to improve functional recovery following nerve injury and repair have included studies of sutureless repairs. The rat sciatic nerve was used as an experimental model to compare the efficacy of laser nerve repairs with standard microsuture repairs. Electrophysiologic (Compound Action Potential), quantitative morphometric, and behavioral (toe spread) measurements were used for assessment, and tensile strength of the repairs was also determined. Electrophysiologic studies showed that microsuture-repaired nerves had significantly faster conduction velocities, but the areas of the waveforms and peak amplitudes showed no significant differences between the two repair groups. Axon counts revealed significant differences in the suture group proximal to the repair site, contrasted with laser repairs. Toe spread evaluations, carried out at three day intervals, demonstrated a significant difference between the two methods of repair in only three out of 22 test dates: in these isolated cases, the suture group measurements were superior. The tensile strength findings confirmed that, at four days, microsuture repair was significantly stronger but thereafter, there was no difference between the two nerve repair techniques.

Adjustment of the myelin sheath to axonal atrophy in the rat spinal root by the formation of infolded myelin loops.

Atrophy of the L4 dorsal and ventral spinal roots was experimentally induced by unilateral sciatic neurectomy in groups of young (2 and 4 months) and older (12 months) albino rats. During the 4 months following neurectomy, the occurrence of infolded myelin loops (IMLs) was quantitatively examined in transverse sections prepared using perfusion fixation with glutaraldehyde and embedding in epoxy resin. The number of IMLs was higher on the operated side and increased with the time of survival and the age of the animals. The formation of IMLs is a characteristic early response of a large-caliber myelin sheath to axonal atrophy, probably reflecting the presence of redundant myelin.

Neurogenically mediated leakage of plasma protein occurs from blood vessels in dura mater but not brain.

Utilizing 125I-BSA administered intravenously, a simple, reliable, and sensitive method was established for the detection of plasma protein extravasation in the dura of rats and guinea pigs following chemical, electrical, or immunological stimulation. Extravasated 125I-BSA or Evans blue was noted in the dura and conjunctiva but not in the temporalis muscle of saline-perfused rats following intravenous capsaicin, 1 mumol/kg. Capsaicin-induced extravasation was mediated by unmyelinated and small myelinated fibers since leakage did not develop in adult animals in whom these fibers were destroyed by capsaicin pretreatment (50 mg/kg) as neonates. An ipsilateral increase in Evans blue and 125I-BSA was found in the dura, eyelids, lips and gingival mucosa, and snout following electrical stimulation of the rat trigeminal ganglion. This increase was also C-fiber dependent. Among those peptides contained in perivascular afferent fibers and administered intravenously, substance P (SP) and neurokinin A (NKA), but not calcitonin gene-related peptide, caused a dose-dependent extravasation in the dura and conjunctiva of rats. Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva. Intravenous administration of 5-HT or bradykinin to normal adult rats or adult rats pretreated as neonates with capsaicin increased levels of 125I-BSA in both the dura and the conjunctiva. Histamine and prostaglandin E2, on the other hand, caused protein leakage in the conjunctiva but not in the dura of rats; however, histamine did induce extravasation in the dura of guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of temporal parameters on subjective sensations evoked by electrical tooth stimulation.

The effect of stimulus duration and frequency on subjective sensations evoked by electrical tooth stimulation was studied in 12 subjects. The sensory responses were classified using 5 equi-sensation categories (perception threshold, prepain, pain threshold, moderate pain, intense pain). Both continuously increasing and randomised stimuli were applied. A comparison was made with the activation thresholds of intradental A- and C-fibres in the cat. The mean threshold of intradental A-fibres was lower than the perception threshold at all pulse durations. Perception threshold decreased with increasing stimulus frequency. Current intensities which evoked prepain at a stimulus frequency of 1 Hz were rated as pain at 20 Hz. At supraliminal pain levels the effects of summation were more marked. High-frequency stimulation produced intense pain sensations at intensities well below the activation thresholds of pulpal C-fibres in the cat. We conclude that both perception and pain thresholds and supraliminal pain are modified by temporal summation, and that activation of different pulpal fibre populations is not responsible for production of prepain and pain sensations.

Contrasting thermal sensitivity of spontaneously active A- and C-fibers in experimental nerve-end neuromas.

Injured afferent A- and C-fibers ending in experimental neuromas in the rat sciatic nerve generate a substantial spontaneous discharge. We show that for individual axons the rate and percent incidence of spontaneous discharge are sensitive to neuroma temperature. Within the range of 14-43 degrees C, firing rate of all of the myelinated fibers examined increased as temperature rose, and decreased as temperature fell. For fibers with a tonic rhythmic discharge pattern, Q10 averaged 1.64 at 34-42 degrees C. Some fibers that were initially silent began to fire as the neuroma was warmed, and some fibers active at baseline temperature fell silent when the neuroma was cooled. Unmyelinated fibers behaved quite differently, showing either no response to temperature changes (44% of fibers sampled), or an increase in discharge rate upon cooling (56%). These effects are probably not secondary to vascular changes, but rather reflect thermal sensitivity of the ectopic neuroma impulse generator sites. This thermal sensitivity may account for the aggravation of phantom limb pain and other neuralgias during cold weather (i.e., post-traumatic cold intolerance).

Small- and large-fiber involvement in early diabetic neuropathy: a study with the medial plantar response and sensory thresholds.

Small- and large-fiber function in diabetic neuropathy was studied in 68 patients (mean age 45.4 +/- 12.9 yr; 27 type I and 41 type II diabetics) with psychophysical tests of vibration and thermal sensation and neurophysiological measurements, including the medial plantar sensory action potential (MPSAP). Thermal sensitivity at the dorsolateral aspect of the foot (Pfizer thermal tester) correlated significantly with vibration thresholds (Somedic vibrameter) at three sites in the foot and two in the hand. Forty patients had normal sensory thresholds, but 18 of these lacked an MPSAP. Smaller groups had a single abnormal sensory threshold: 12 (18%) had an abnormal vibration threshold, and 24 (35%) had abnormal thermal sensitivity; 8 of the former group and 17 of the latter group lacked an MPSAP response. Only 8 (12%) had both abnormal vibration and thermal sensation (6 without an MPSAP). Fifteen of the 17 symptomatic patients had lost the MPSAP, but there was no consistent pattern of sensory loss. In this relatively young group of diabetics, more patients showed absent MPSAP responses than an abnormality in either sensory test on its own. The MPSAP is frequently absent in patients with no abnormalities in psychophysical tests of peripheral large-fiber function (vibration sensation) and small-fiber function (thermal sensitivity).

Discharge patterns of afferent cutaneous nerve fibers from the rat's tail during prolonged noxious mechanical stimulation.

Feedback controlled constant force stimuli of 4, 6 and 8 N intensities and of 120 s duration were applied to the receptive fields of cutaneous afferent fibers in the rat's tail. Two types of nociceptive units showed sustained discharges during these stimuli: "polymodal" unmyelinated C-units (MH-C units, N = 18, c.v. 0.5-0.9 m/s) and high-threshold mechanoreceptive A-delta-units (HTM-units, N = 10, c.v. 1.9-11.2 m/s). In addition two classes of sensitive low threshold mechanoreceptors, SA I (N = 6) and SA II (N = 5) units, responded to the prolonged mechanical stimuli. At the onset of a noxious pressure, 11 of the 18 polymodal nociceptors exhibited dynamic responses (lasting about 10 s) which were followed by slowly adapting tonic discharges that lasted for the duration of the stimuli. The remaining polymodal C-fiber units (8/18) did not show dynamic discharges at 4 and 6 N. Phasic and tonic discharges were positively correlated with stimulus strength. The HTM-units encoded stimulation intensity mainly by their dynamic discharges. The tonic discharges of these units displayed faster adaptation rates with stronger mechanical stimuli, i.e. encoding of stimulation intensity became progressively weaker during the tonic phase. The discharges of sensitive SA I and SA II units with A beta axons were not positively correlated with the strength of noxious pressure stimuli. Tonic discharge rates of SA I units were negatively correlated to stimulus strength, whereas SA II units usually stopped firing in the course of a stimulus and became reversibly irresponsive to mechanical stimulation. Possible afferent mechanisms underlying the induction of pain by sustained noxious mechanical stimulation are discussed.

Effects of potassium channel-blocking agents on spontaneous discharges from neuromas in rats.

Thirty-five Sprague-Dawley rats with saphenous neuromas underwent acute microfilament recording in the proximal nerve. The effect of the potassium channel-blocking agents, tetraethylammonium bromide (TEA) and 4-aminopyridine, on spontaneous activity in A fibers terminating in the neuroma was observed. The effects of gallamine were also tested. Of the two channel-blocking agents, TEA reliably increased spontaneous firing in active fibers and initiated spontaneous activity in some fibers with no spontaneous baseline discharge. 4-Aminopyridine had no effect on baseline activity of either spontaneously active or quiescent fibers: however, it inhibited spontaneous activity induced by prior TEA treatment. Gallamine application produced effects similar to TEA in that spontaneous activity was dramatically increased. These results imply that a tonic potassium conductance is present in regenerating fibers in the neuroma and that this conductance moderates the tendency toward hyperexcitability and spontaneous firing. Spontaneous activity in nociceptive afferent fibers may represent the mechanism of chronic pain and paresthesias that often accompany peripheral nerve injury. These results suggest that agents which either increase potassium conductance or selectively inhibit the sodium current in regenerating axons might be effective in the treatment of these chronic pain syndromes.

A note on the mechanism of resistance to anoxia and ischaemia in pathophysiological mammalian myelinated nerve.

Computer simulation of the action potential in myelinated nerve fibres show that the metabolic cost of conduction of an impulse is less than normal in a slightly depolarised fibre. This would account, at least in part, for the greater resistance to ischaemia and anoxia of nerves from diabetics and other pathophysiological conditions.

Membrane ultrastructure of developing axons in glial cell deficient rat spinal cord.

In order to investigate axolemmal development in a glial cell deficient environment, normal and irradiated dorsal funiculus in rat lumbosacral spinal cord was examined by freeze-fracture electron microscopy. At 3 days of age, normal fibres are all unmyelinated and of small (less than 0.5 micron) diameter. The unmyelinated axons have a moderate density (approximately 850 microns-2) of intramembranous particles (IMPs) on P-fracture faces and a low IMP density (approximately 300 microns-2) on E-faces. IMPs are homogeneously distributed along both fracture faces. By 19 days of age, the normal dorsal funiculus is well populated with myelinated axons and glial cells, as well as a sizable population of unmyelinated fibres. Nearly all of the myelinated fibres have a large (greater than 1.0 micron) diameter; whereas, most unmyelinated axons are of small (less than 0.5 micron) calibre. The axolemma of unmyelinated axons is relatively undifferentiated, with an asymmetrical distribution of IMPs (P-face: approximately 1100 microns-2; E-face: approximately 450 microns-2). Myelinated fibres show nodal and paranodal regions with P-face and E-face ultrastructure similar to previous descriptions. Internodal axolemma appears relatively homogeneous, with P-faces being highly particulate (approximately 2100 microns-2) and a low IMP density (approximately 200 microns-2) on E-faces. Following irradiation of the lumbosacral spinal cord at 3 days of age, there is a severe reduction in the number of glial cells and myelinated fibres in this region when the tissue is examined at 19 days of age. Despite the deficiency of glial cells in this tissue, axonal and axolemmal development continue. Numerous large (greater than 1.0 micron) diameter axons are present in this irradiated tissue. Large diameter axons show a high (approximately 2000 microns-2) density of IMPs on P-faces; E-face IMP density remains at approximately 440 micron-2. Small calibre axons also have an asymmetrical distribution of particles (P-face: approximately 1100 microns-2; E-face: 280 microns-2). The axolemmal E-faces of some glial cell deprived fibres exhibit regions with greater than normal (approximately 750 microns-2) density of IMPs. These results demonstrate that some aspects of axonal and axolemmal development continue in a glial cell deficient environment, and it is suggested that axolemmal ultrastructure is, at least in part, independent of glial cell association.

Reactions of cardiac postganglionic sympathetic neurons to movements of normal and inflamed knee joints.

The effects of passive movements of normal and inflamed knee joints on unitary activity in filaments of the inferior cardiac nerve (ICN) were studied in cats anesthetized with chloralose and urethane. The effects were compared with those obtained by electrical stimulation of afferent A- and C-fibers in the medial articular nerve, in muscle and in cutaneous hind limb nerves. The vagus nerves were cut and the right carotid artery was tied off. The left carotid sinus was intact. All ICN units used in this study displayed spontaneous activity which was usually related to the cardiac and respiratory rhythms. The ICN units were regularly excited by electrically evoked single or short repetitive A-volleys in articular, cutaneous and muscle nerves. The excitation was followed by a silent period. Inclusion of C-fibers in the afferent volleys gave a second, long-latency burst of impulses which was seen only with short repetitive stimulation. Passive movements in the normal working range of the joint did not influence the activity of ICN units. However, noxious joint movements, particularly of inflamed joints, led to pronounced excitation of ICN units accompanied by rises in blood pressure. Most of these effects could still be seen after all nerves to the hind limbs, except the medial articular nerve, were cut. It is proposed (a) that ICN units form a homogeneous population of sympathetic postganglionic units whose reaction pattern to somatovisceral input is distinctly different from that of other sympathetic subsystems, and (b) that articular receptors make a substantial contribution to the ICN input particularly when many fine afferent units are sensitized to mechanical stimulation by an acute joint inflammation.

Excitation of tooth pulp afferents with electrical current.

Electrical excitation of tooth pulp afferents seems to be a most accurate and reproducable method to produce graded pain with minimal injury of the tissues. Besides electrical current only thermal stimulation may activate pulp nerves of an intact tooth, but this method lacks the precision of the electrical stimulation and bears more risk of injury. Surrounded by enamel of high resistance and capasitance the pulp nerves are difficult stimulation objects. On the other hand with careful stimulation the current is almost completely restricted to the pulp. The square wave current pulse is "deformed" according to the time constant of hard tissues and exceptionally long durations are needed. There is ultimate necessity for constant current stimulation because of varying anatomy and resistance of the teeth. When different amplitudes and durations of current pulses are used to compare perception thresholds of human teeth and firing thresholds of single pulp nerve fibres of the cat, it may be concluded that "prepain" sensation is experienced using current values that activate only A-fibres. To attain the pain threshold, recruitment of more A-delta fibres with increasing current is needed, but the lowest thresholds of C-fibres are even higher.

[Electrophysiologic study of Achilles areflexia of aged subjects]. / Etude électrophysiologique de l'aréflexie achilléenne du sujet âgé.

The elderly often presents loss of Achilles tendon reflex. In this electrophysiological study the authors examined 19 patients with loss of the ankle jerk and with no known etiology of peripheral neuropathy. They compared them with 24 subjects who had no areflexia. The study included measurement of the H reflex, of the tendon reflex, of the conduction velocity of Ia fibers and of motor conduction velocity of the tibial nerve. Amplitude of H and tendon response and H/M ratio are diminished in the areflexic group. In 4 cases the H reflex is preserved while the tendon reflex is abolished. The meaning of these impairments is discussed.