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Biomedical subjects

P Marchettini

Publications and source records attributed to P Marchettini.

At least 37 records · Page 2Linked to original sources

Evidence of peripheral axonal neuropathy in primary restless legs syndrome.

Restless legs syndrome (RLS) is a well-defined clinical entity characterized by an unpleasant creeping sensation arising in the legs with an irresistible need to move them. The trouble is more pronounced when the affected people lie in a prolonged rest position and try to fall asleep. It is known that RLS may be consequent to systemic disorders and to diseases affecting the central or peripheral nervous system. The International Classification of Sleep Disorders states that peripheral neuropathy should be ruled out by medical history and clinical grounds before diagnosing primary RLS (pRLS). The present study extended peripheral nerve investigation in eight consecutive pRLS patients with normal neurological examination results and showed that all patients exhibited two or more electrical, psychophysiological, and/or morphological features of peripheral axonal neuropathy. Morphometric analysis of sural nerve showed a significant reduction in myelinated fiber density and g ratio (axon diameter/fiber diameter) in the pRLS group compared with eight control biopsy specimens. These results suggest that axonal neuropathy is often present in patients with RLS. A comprehensive peripheral nerve investigation should be considered in RLS patients.

Adult↗

Different time-courses of i.v. lidocaine effect on ganglionic and spinal units in neuropathic rats.

The effect of intravenous lidocaine (4 mg kg-1) on ganglionic and spinal neuronal hyperactivity following sciatic chronic constriction injury (CCI) was studied in anaesthetized and curarized rats. A significant difference in the time course and magnitude of the lidocaine effect on the two neuronal populations was found. Longer lasting and more potent inhibitory effects on the dorsal horn neurones in comparison with ganglionic neurones were observed. By contrast the magnitude and time course of the inhibitory effects were highly comparable in dorsal horn neurones before and after acute rhizotomy. The results indicate that peripheral and central effects of lidocaine are not sequentially related. The likelihood that lidocaine inhibition at central sites may have a role in its analgesic effect, at least in the neuropathic model, is discussed.

Animals↗

Identification of muscle afferents subserving sensation of deep pain in humans.

1. Intraneural microstimulation (INMS) and microneurography were used in combination to stimulate and record from muscle nociceptor primary afferent fibers of the common peroneal nerve of healthy volunteers. When pain evoked by INMS was projected to muscle, afferent activity could be evoked by innocuous and noxious pressure applied within the projected painful area. Conduction velocity of single fibers was determined by stimulating the receptive fields (RFs) electrically via needle electrodes inserted into the RF and measuring conduction latency and distance between the RF and recording electrode. 2. Pain projected to muscle during INMS trains 5-10 s in duration at threshold intensity for pain sensation was typically described as cramping and was well localized. Subjects mapped the area of the painful projected field (PF) over the skin using a pointer. 3. Fourteen slowly adaping mechanoreceptors with RF in muscle and with moderate to high receptor threshold were identified within or near the painful PF. Conduction velocities were in the range of Group III (n = 8) and Group IV (n = 6) fibers. Mean RF areas of Group III and Group IV afferents, determined by applying pressure percutaneously, were 2.71 +/- 1.14 (SE) cm2 and 3.40 +/- 1.08 (SE) cm2, respectively. Only one Group III afferent unit exhibited spontaneous activity (< 1 Hz). 4. One additional high-threshold mechanoreceptor was identified, with its RF located in the extensor tendon at the base of the big toe. This fiber had a conduction velocity of 32 m/s. During INMS, a well-localized sharp pain was projected to the tendon.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diverse modulation by systemic lidocaine of iontophoretic NMDA and quisqualic acid induced excitations on rat dorsal horn neurons.

The effects of systemic lidocaine (3-4 mg/kg) on the responses of 60 wide dynamic range neurons (WDR) to iontophoretically applied N-methyl-D-aspartic acid (NMDA) and quisqualic acid (QUIS) were studied in anesthetized, paralysed rats. The results show that lidocaine induced (i) potentiation of the NMDA excitation, reversible by 7-chloro-kynurenate (7-Cl-KYNA), a selective antagonist of the glycine binding site on the NMDA receptor; (ii) reduction of the QUIS excitation, reversible by strychnine (STRYCH), a glycine antagonist at its receptor. These findings, supporting a glycine-like action of lidocaine, are discussed together with data on the role of excitatory amino acids (EAAs) and the analgesic effect of lidocaine on neuropathic pain.

Animals↗

Muscle pain: animal and human experimental and clinical studies.

The search for the identification of the sensory apparatus encoding muscle pain sensation in humans is recounted. Basic neurophysiologic animal studies, leading to a description of slowly conducting afferent from muscle and definition of high threshold polymodal muscle nociceptors, and pioneer psychophysic human studies together with recent microneurographic experiments in humans are described. The phenomena of muscle pain broad localization and distant referral are discussed, and clinical implications are extrapolated to interpret muscle pain as a localizing sign of mononeuropathy or radiculopathy. The identification of human muscle nociceptors has defined the scientific standard to test emerging clinical descriptions having muscle pain as a symptom.

Animals↗

Effect of hypothyroidism on rat peripheral nervous system.

The function and structure of the peripheral nervous system of Sprague-Dawley rats, 3 months after the induction of hypothyroidism by administration of N-propylthiouracil in drinking water, has been studied. The motor action potential amplitude of the caudal nerve showed a significant reduction (p < 0.001) when compared with an age-matched control group of animals. Computer-assisted morphometric analysis of sciatic nerves of hypothyroid rats showed normal distribution and density of myelinated fibers, and a normal axon/myelin ratio. Electron microscopy revealed only minor alterations in axons of myelinated fibers characterized by a dissolution of neurotubules. After two months of substitution therapy these effects were reversed. The present data suggest that early impairment of nerves induced by hypothyroidism is rare and could be related to metabolic alterations rather than to structural changes and is reversible with hormone treatment.

Action Potentials↗

Effect of systemic lidocaine on dorsal horn neuron hyperactivity following chronic peripheral nerve injury in rats.

Systemic lidocaine (3-4 mg/kg) was tested for its effect on identified spinal cord wide-dynamic-range (WDR) neurons in rats with a unilateral chronic neuropathy induced by two different peripheral nerve injuries (section or compression by ligatures). In both cases, neurons on the side ipsilateral to the injuries showed a spontaneous firing frequency higher than that of the opposite intact side (23.5 +/- 3.4 vs 4.2 +/- 1.5 spikes/sec). The hyperactivity was not affected by a sensory block of the peripheral receptive field. It was consistently found that lidocaine suppressed or reduced the spontaneous neuronal hyperactivity on the ipsilateral side, whereas it had no effect on the normal spontaneous activity of the neurons on the intact side. In all recordings, the hyperactivity returned to the prelidocaine injection rates within 20 min. These results indicate a preferential action of subanesthetic doses of lidocaine on the hyperactive WDR neurons. Such preferential action is related to a susceptibility acquired by WDR neurons of the peripherally injured side and is not simply attributable to the increased frequency of firing.

Animals↗

Selective inhibition by systemic lidocaine of noxious evoked activity in rat dorsal horn neurons.

The effect of systemically injected lidocaine (3-4 mg kg-1) on the responses to noxious and non-noxious stimuli on 28 wide dynamic range (WDR) neurons in the dorsal horn was studied in anesthetized and curarized rats. It was consistently found that lidocaine reduced or suppressed the responses to noxious stimuli whereas it did not act on the responses to non-noxious stimulation and on the spontaneous activity. Furthermore the noxious stimuli were completely ineffective from 10-15 min following the lidocaine injection while the non-noxious stimuli maintained their efficacy. The control responses, in all the cases, returned within 20 min. The results suggest that lidocaine exerts a selective inhibitory effect on nociceptive transmission at the spinal level.

Animals↗

Morphological and functional evaluation of peripheral nerve regeneration in the rat using an expanded polytetrafluoroethylene (PTFE) microprosthesis.

The aim of our study was to evaluate in the rat the ability of a polytetrafluoroethylene microprosthesis (PTFE), to guide the peripheral nerve regeneration between the two extremities of a transected sciatic nerve. In 15 adult male Wistar rats, weighing 200 g, a segment of the right sciatic nerve was resected, leaving a gap of about 1 cm, bridged with microprosthesis, using our original microsurgical technique. Neurophysiological evaluations were performed at 6 and 9 months post-operatively to study the distal motor latency either in the right sciatic nerve or in the unoperated control side. In all the rats myoelectrical responses with an increased latency of the operated side were produced from the interosseous muscle of the foot. The animals were sacrificed 9 months post surgery. Histological sections at the level of the graft were done in all the rats, and in 10 animals biopsies of the tibialis anterior muscle (TA) of each side were performed. An active process of axonal regeneration was documented inside the graft, with no infiltration of nerve fibers through the wall of the prosthesis. A connective fibrous reaction was present around the external wall of the graft. Muscle biopsies showed definite signs of muscle reinnervation, with residual features of variable degree of denervation. These findings stress and confirm the ability of the PTFE graft to allow effective regeneration in a peripheral nerve gap in the rat.

Animals↗

Innervation territories for touch and pain afferents of single fascicles of the human ulnar nerve. Mapping through intraneural microrecording and microstimulation.

The peripheral distribution of the fibre content of individual ulnar nerve fascicles supplying skin and muscles of the hand in human volunteers was indirectly mapped by tracing the fields of projected sensation evoked by intraneural electrical microstimulation (INMS) and by tracing receptive fields delineated through intraneural recording of afferent impulse activity elicited by natural stimulation of end organs. Moderate intensity suprathreshold INMS, delivered in cutaneous fascicles, induced nonpainful sensations projecting to stereotyped and coherent areas of skin, the fascicular projected fields (FPFs). Fascicular receptive fields (FRFs) were mapped during microneurographic recording by determining the area of skin which, when activated by light tactile stimuli, elicited afferent neural discharges recorded intraneurally. It was found that at a given electrode position in a skin nerve fascicle, moderate intensity INMS induced nonpainful sensations projecting to a cutaneous field (FPF) that coincides with the FRF, while high intensity INMS induced painful sensations projecting within the cutaneous field of nonpainful sensations. Pain induced by INMS in muscle nerve fascicles was projected to the muscles innervated by that fascicle and, in most instances, to areas beyond the muscular receptive field. The study demonstrates that individual ulnar nerve fascicles, at wrist levels, subserve well-defined cutaneous territories in the hand, and that the area of skin covered by the sum of all ulnar fascicular receptive or projected fields matches the maximal possible cutaneous distribution of the ulnar nerve. Insights of practical relevance regarding clinical expression of fascicular nerve injuries are also brought up by this study.

Adult↗

Sympathetic neural outflow directly recorded in patients with primary autonomic failure: clinical observations, microneurography, and histopathology.

We evaluated 2 patients with primary autonomic failure, without clinical peripheral neuropathy. One had primary autonomic failure alone (PAF), and the other had autonomic failure and multiple system atrophy (MSA). Direct intraneural recordings demonstrated a marked reduction of sympathetic efferent nerve impulse activity in the PAF patient. The patient with MSA had spontaneous bursts of sympathetic nerve impulses that confirmed the functional integrity of post-ganglionic sympathetic efferent neurons. Neurosecretory activity of these neurons correlated with the electrophysiologic findings. The PAF patient had markedly reduced supine norepinephrine (NE) levels that did not rise upon standing. The supine NE level in the MSA patient was normal. Morphometric study of biopsied sural nerve in the MSA patient showed that unmyelinated fibers were normal, whereas the nerve of the PAF patient showed clear evidence of past degeneration. We suggest that the primary preganglionic sympathetic defect in MSA releases viable postganglionic sympathetic efferents from central control. Decentralized postganglionic elements may fire spontaneously, thus activating peripheral effectors and providing potentially useful signs and symptoms for differential diagnosis.

Autonomic Fibers, Postganglionic↗

Peripheral nerve damage during limb lengthening. Neurophysiology in five cases of bilateral tibial lengthening.

Limb lengthening is used to correct leg length discrepancy and to increase stature. The reported frequency of peripheral nerve complications varies from 5% to 30%, but is probably underestimated. Damage may be direct or be caused by overstretching of the nerves. We have used electrophysiological tests to evaluate five patients during bilateral tibial lengthening by the Ilizarov method. Results after 24 to 107 days of lengthening showed electromyographic evidence of partial muscle denervation in all 10 limbs, with reduced motor conduction velocities in two tibial nerves and three common peroneal nerves. The sensory conduction velocity in the sural nerve was always unchanged. A clear relationship was shown between the amount of tibial lengthening and the degree of electrophysiological abnormality. Our results suggest that subclinical nerve damage is a very frequent complication of tibial lengthening.

Action Potentials↗

Does acute intraoral pain alter cutaneous sensibility?

Cutaneous sensibility was tested in eight patients suffering from acute postoperative intraoral pain. Tactile-, cold-, warm-, and heat-pain thresholds as well as reaction time to cold pulses were unaffected by the presence of pain. However, reaction time to warm pulses was increased in the painful area on the day of pain compared to a non-painful state. The findings are discussed in relation to (1) functional convergence of different sensory fibres on central neurons (2) the phenomenon of diffuse noxious inhibitory controls and (3) secondary hyperalgesia. The observed effect of clinical pain on the warm pathway could be explained as an intrasegmental noxious inhibitory effect.

Adolescent↗

Cognitive deficits and their relationship to other neurological complications in chronic alcoholic patients.

In randomly selected chronic alcoholics hospitalised for the first time for detoxification a high prevalence (68%) of cognitive deficits was found. Peripheral neuronal damage was seen in 74%, autonomic neuronal damage in 24%. Cognitive deficits were not correlated with age, daily ethanol intake, duration of alcohol abuse or severity of liver damage. There was no correlation of peripheral, autonomic and central nervous system damage. Alcohol-induced damage of the nervous system is a common complication of chronic alcoholism, whose clinical importance often obscures possible concomitant liver damage.

Adult↗