Biomedical subjects

Z Seltzer

Publications and source records attributed to Z Seltzer.

27 records · Page 2Linked to original sources

PubMed1988

Lack of sensitization of primary afferent receptors by prostaglandins in a rat model of causalgic chronic pains.

Unilateral entrapment of half of the sciatic nerve in a ligature rapidly produces in rats bilateral hyperalgesia: decreased withdrawal thresholds to von-Frey hair touch and to noxious CO2 laser heat pulses and unilateral hyperpathic responses to a supra-maximal noxious heat pulse. These abnormal pain responses last many months and are very similar to those seen in humans with causalgia. In the present study we determined whether the underlying mechanism involves bilateral sensitization of primary afferent receptors. Since the responses of rats with partial sciatic injury to stimulation of rostral areas (forepaws, muzzle and auricles) were normal, we presume that the hyperalgesia at the contralateral hindpaw could not be due to receptor sensitization, but to rapid central plasticity. Moreover, since indomethacin did not prevent the bilateral hyperalgesia, we conclude that the causalgiform pain disorders seen in the ipsilateral hindpaw did not derive from receptors sensitized by prostaglandins.

Animals↗

PubMed1988

Effect of hyperglycemia on pain perception and on efficacy of morphine analgesia in rats.

The effect exerted by different hyperglycemic states on the pain threshold and on the analgesic potential of morphine was studied in male Sabra rats with the hot plate device. Hyperglycemia induced by an intraperitoneal injection of 0.014 mol/kg glucose or an acute or chronic diabetic state induced by streptozocin injection did not significantly alter the pain threshold. However, states of acute and chronic diabetes markedly blunted the analgesic effect of morphine (5 mg/kg). Sabra rats maintained on a cocktail of glucose-saccharin, thought to activate the release of endogenous opioids, demonstrated an increased pain threshold and rapidly developed resistance to the analgesic effect of morphine. Previous studies have shown that glucose in high concentration may interfere with the interaction of morphine on the opiate receptor. The influence of the diabetic state on beta-endorphin synthesis and concentration in the central nervous system is another factor that might change pain perception in diabetes. We propose that in diabetes, generally, the pain threshold is adequately maintained, despite the antagonistic effect of glucose, partly due to a compensatory increased secretion of endogenous opioid peptides. We hypothesize that in patients with chronic painful diabetic neuropathy, these normal analgesic response mechanisms may be overwhelmed either by an excess of nociceptive impulses from diseased peripheral nerves or conceivably by a failure of endogenous opioid secretory response to the hyperglycemia.

Action Potentials↗

PubMed1985

A chronically implanted delivery system of drugs to a nerve-end neuroma: effects on a behavioural chronic pain model.

Autotomy has been suggested as an animal model of chronic pain. It starts about a week or two postoperatively and develops until 10 weeks after nerve section. This behaviour is thought to be triggered by activity of sensory fibres ending in a neuroma. Here we suggest to utilize it in combination with a novel drug delivery system which enables a direct and exclusive access of the drug to the neuroma. Alteration in the autotomy behaviour can then be related to the exclusive topical action on the sensory fibres within the neuroma. The sciatic nerve is transsected and its proximal end inserted into a PE tube sealed distally. A second, smaller tube originates in a wound exit in the back of the animal and subcutaneously leads into the large tube, where it is fixed by glue to the inner wall. Thus, the end of the smaller tube is juxtaposed to the nerve end. During the following weeks a neuroma develops within the tube. The resulting autotomy scores are then examined weekly. At various times after the operation, under light anaesthesia, drugs can be injected into the tube and the effect on the autotomy behaviour is monitored. An example is given, describing the autotomy suppressive effects of glycerol and alcohol, injected to different groups of rats immediately after the operation and compared to an injection 14 days postoperatively. This method is suggested as a pharmaco-behavioural assay for the assessment of the analgetic efficacy of drugs for chronic pain.

Amputation Stumps↗

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

The cells of origin of the dorsal column postsynaptic projection in the lumbosacral enlargements of cats and monkeys.

Dorsal column postsynaptic (DCPS) neurons in the lumbosacral enlargements of cats and macaque monkeys were retrogradely labeled by placing HRP on their severed axons within the dorsal columns. The enlargements of both species contained 800-1,100 labeled DCPS neurons. The DCPS projection is thus as large as the feline spinocervical tract. It is very probable that most of these neurons project to the dorsal column nuclei and thereby constitute one of the major sources of somatosensory input to the brain. In the cat, DCPS neurons were concentrated in a band centered in lamina IV that swept down through laminae V-VI along the medial border of the dorsal horn. A second concentration of labeled cells was found in dorsomedial lamina VII. In the monkey, DCPS neurons were concentrated in a relatively broader band in laminae III-IV, and scattered cells were consistently observed throughout laminae V-VII and X and in the dorsolateral white matter. The prominence of the monkey's DCPS projection suggests that humans also have such a projection.

Animals↗

PubMed1979

Two modes of cutaneous reinnervation following peripheral nerve injury.

The return of sensation to the foot following sciatic nerve crush injury was analyzed behaviorally and electrophysiologically in the rat. Functional recovery begins within four days. Its early phase is accounted for by expansion of the functional distribution of intact neighboring fibers of the saphenous n. It occurs even if the sciatic n. is ligated, and it disappears with section of the saphenous n. Accompanying this functional expansion we began to encounter in electrophysiological recordings from the saphenous n., fibers with unusually large receptive fields (RF's) extending onto the plantar surface of the foot, well beyond their limits in intact rats. All of the expanded RF's were high threshold mechanoreceptors. On about the twentieth day after crushing, the regenerating sciatic n. began to make a functional contribution. This was seen by return of sensation to zones not invaded by the saphenous n. and by the onset of sensation in rats in which the saphenous n. had previously been ligated. With return of the sciatic n. the expanded distribution of the saphenous n. went back to its original boundaries. Correspondingly, we could no longer find expanded saphenous n. RF's. We conclude that cutaneous reinnervation begins with the collateral expansion of high threshold afferents from intact neighboring nerves. This alien innervation is later replaced upon regeneration of the original nerve.

Animals↗

PubMed1979

Autotomy following peripheral nerve lesions: experimental anaesthesia dolorosa.

(1) When hindlimb peripheral nerves are cut across in rats and mice, there is a tendency for the animal to attack the anaesthetic limb. We have called this attack "autotomy". In this paper we describe the time course and degree of autotomy following various types of nerve injury. (2) Four different types of lesion were applied to the sciatic nerve of rats. The most serious autotomy was produced by section of the nerve and encapsulation of its cut end in a polythene tube. Section followed by immediate resuturing also produced serious autotomy. Simple ligation of the nerve end was followed by less autotomy than encapsulation or cut and resuture. A crush lesion caused only minimal attack. (3) Section of the saphenous branch of the femoral nerve produced no autotomy. However, if the saphenous and sciatic nerves were ligated at the same time so that the entire foot became anaesthetic there was a great increase of autotomy over that seen when the sciatic nerve alone was ligated. This increase with the double lesion occurred even if the saphenous nerve was ligated more than 100 days after the sciatic nerve had been cut. (4) Mice showed autotomy very similar to that seen in rats but the onset was somewhat faster. (5) Reasons are given to propose that autotomy is triggered by an abnormal afferent barrage generated in the cut end of the nerve. Autotomy from peripheral nerve lesions is a different phenomenon from that seen after dorsal root section. Autotomy occurs under conditions which produce anaesthesia dolorosa in man. This simple model may be suitable for studies of the prevention of irritations originating from chronic lesions of peripheral nerves.

Animals↗

PubMed1979

Ephaptic transmission in chronically damaged peripheral nerves.

Several weeks after damage of the sciatic nerve in adult rats, a stable electrical (ephaptic) interaction forms between pairs of injured sensory and motor axons. Fiber-fiber interaction occurs when the nerve ends in a neuroma, after end-to-end nerve suture and after nerve crush injury. Unlike the transient "artificial synapse" created acutely on section of a nerve, this form of crosstalk is long-lasting. Its existence lends support to the hypothesis that ephaptic interaction is an important factor in neurologic pathophysiology.

Animals↗

PubMedDate not supplied

Sympathetically-maintained causalgiform disorders in a model for neuropathic pain: a review.

Partial nerve injury is the main cause of sympathetically maintained causalgiform pain disorders in humans. We present here an animal model of this condition, produced in rats by a unilateral ligation of about half of the sciatic nerve. Starting hours after the operation and for several months thereafter, the rats developed signs of spontaneous pain, touch-evoked allodynia and hyperesthesia, and mechanical and thermal hyperalgesia in the partially denervated as well as the intact contralateral foot. These disorders were maintained by the sympathetic outflow and disappeared following postoperative sympathectomy. In neonatally capsaicinated rats we found that touch-evoked allodynia and hyperesthesia were mediated by A-fibers whereas thermal hyperalgesia was mediated by C-fibers. These disorders were not due to receptor sensitization of remaining afferent fibers by prostaglandins. We found strain differences and genetic inheritance of these causalgiform disorders which were correlated with the expression of autotomy to hind-paw denervation.

Animals↗