Search

In the anesthetized cat the correlation between the ongoing cord dorsum potentials (CDPs) recorded from different lumbar spinal segments has a non-random structure, suggesting relatively stable patterns of functional connectivity between the dorsal horn neuronal ensembles involved in the generation of these potentials. During the nociception induced by the intradermic injection of capsaicin, the patterns of segmental correlation between the spontaneous CDPs acquire other non-random configurations that are temporarily reversed to their pre-capsaicin state by the systemic injection of lidocaine, a procedure known to decrease the manifestation of neuropathic pain in both animals and humans. We have now extended these studies and utilized machine learning for the automatic extraction and selection of particular classes of CDPs according to their shapes and amplitudes. By using a Markovian analysis, we disclosed the transitions between the different kinds of CDPs induced by capsaicin and lidocaine and constructed a global model based on the changes in the behavior of the CDPs generated along the whole set of lumbar segments. This allowed the identification of the different states of functional connectivity within the whole ensemble of dorsal horn neurones attained during nociception and their transitory reversal by systemic administration of lidocaine in preparations with the intact neuroaxis and after spinalization. The present observations provide additional information on the state of self-organized criticality that leads to the adaptive behavior of the dorsal horn neuronal networks during nociception and antinociception both shaped by supraspinal descending influences., (Copyright © 2019 Martín, Béjar, Chávez, Ramírez-Morales, Hernández, Moreno, Contreras-Hernández, Glusman, Cortés and Rudomin.)

In a previous study we developed a Machine Learning procedure for the automatic identification and classification of spontaneous cord dorsum potentials ( CDPs ). This study further supported the proposal that in the anesthetized cat, the spontaneous CDPs recorded from different lumbar spinal segments are generated by a distributed network of dorsal horn neurons with structured (non-random) patterns of functional connectivity and that these configurations can be changed to other non-random and stable configurations after the noceptive stimulation produced by the intradermic injection of capsaicin in the anesthetized cat. Here we present a study showing that the sequence of identified forms of the spontaneous CDPs follows a Markov chain of at least order one. That is, the system has memory in the sense that the spontaneous activation of dorsal horn neuronal ensembles producing the CDPs is not independent of the most recent activity. We used this markovian property to build a procedure to identify portions of signals as belonging to a specific functional state of connectivity among the neuronal networks involved in the generation of the CDPs . We have tested this procedure during acute nociceptive stimulation produced by the intradermic injection of capsaicin in intact as well as spinalized preparations. Altogether, our results indicate that CDP sequences cannot be generated by a renewal stochastic process. Moreover, it is possible to describe some functional features of activity in the cord dorsum by modeling the CDP sequences as generated by a Markov order one stochastic process. Finally, these Markov models make possible to determine the functional state which produced a CDP sequence. The proposed identification procedures appear to be useful for the analysis of the sequential behavior of the ongoing CDPs recorded from different spinal segments in response to a variety of experimental procedures including the changes produced by acute nociceptive stimulation. They are envisaged as a useful tool to examine alterations of the patterns of functional connectivity between dorsal horn neurons under normal and different pathological conditions, an issue of potential clinical concern.

Previous studies aimed to disclose the functional organization of the neuronal networks involved in the generation of the spontaneous cord dorsum potentials (CDPs) generated in the lumbosacral spinal segments used predetermined templates to select specific classes of spontaneous CDPs. Since this procedure was time consuming and required continuous supervision, it was limited to the analysis of two specific types of CDPs (negative CDPs and negative positive CDPs), thus excluding potentials that may reflect activation of other neuronal networks of presumed functional relevance. We now present a novel procedure based in machine learning that allows the efficient and unbiased selection of a variety of spontaneous CDPs with different shapes and amplitudes. The reliability and performance of the present method is evaluated by analyzing the effects on the probabilities of generation of different classes of spontaneous CDPs induced by the intradermic injection of small amounts of capsaicin in the anesthetized cat, a procedure known to induce a state of central sensitization leading to allodynia and hyperalgesia. The results obtained with the selection method presently described allowed detection of spontaneous CDPs with specific shapes and amplitudes that are assumed to represent the activation of functionally coupled sets of dorsal horn neurones that acquire different, structured configurations in response to nociceptive stimuli. These changes are considered as responses tending to adequate transmission of sensory information to specific functional requirements as part of homeostatic adjustments.

Unlabelled: Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states., Implications: Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.

Background: Acute lower extremity paralysis secondary to lumbosacral plexopathy is a rare but severe complication that may follow pelvic radiotherapy for cervical cancer., Case: A 49-year-old female with newly diagnosed stage IIIB cervical cancer developed progressive bilateral lower extremity paralysis and pelvic pain only 10 weeks following completion of radiation therapy for cervical cancer with no evidence of metastasis or progression of disease. Her bladder and bowel function were not affected. Following extensive workup, the most likely etiology was presumed radiation-induced lumbosacral plexopathy., Conclusion: Although metastatic carcinoma is more commonly the reason for progressive lower extremity weakness with pelvic pain in women with advanced cervical cancer, radiation-induced lumbosacral plexopathy, a rare but devastating complication, may be the cause. Diagnosis is by exclusion., (Copyright 1999 Academic Press.)

The involvement of the adenylate cyclase system in myocardial depression by halothane was investigated in an isolated, electrically stimulated, rat left atrial preparation. The twitch tension dose-response curve to the muscarinic agent, carbachol, was unaltered by 0.27 mM (0.8%) halothane. Pertussis toxin irreversibly blocks the inhibition of adenylate cyclase by muscarinic agonists. Atria from animals pretreated with pertussis toxin were insensitive to the negative inotropic effect of carbachol, but the depression in twitch tension by halothane was unaltered. Halothane shifted the dose-response curve to isoproterenol downward and to the right. However, the depression in twitch tension by 0.27 mM halothane was similar in preparations incubated with the nonhydrolyzable cAMP analogue, dibutyryl-cAMP, compared to control atria stimulated with isoproterenol. We conclude that halothane attenuates the response to beta-adrenergic stimulation in myocardial tissue, and alterations in adenylate cyclase activity do not contribute significantly to this process.

The aim of this study was to identify changes in Müller cell plasma membrane specializations during experimentally induced subretinal gliosis in rabbits. When rabbits are dosed with sodium iodate, large expanses of retinal pigment epithelium and photoreceptors are destroyed. They are replaced by a subretinal scar consisting mainly of the ascending processes of Müller cells. These processes transform from the slender, highly polarized structures seen in normal animals into irregular processes that form a glia limitans along the basement membrane of the pigment epithelium, left bare following its degeneration. As the scar processes extend through the subretinal space and contract this basement membrane, they undergo dramatic changes in shape that are especially apparent in three-dimensional computer reconstructions of serial thick sections examined by high-voltage electron microscopy. Other changes involve the intercellular junctions and apical microvilli normally associated with the external limiting membrane. These structures become scattered over the surfaces of the ascending processes and are eventually lost. Loss of microvilli is associated with disappearance of immunostaining for a specific glycoconjugate normally associated with the microvillar plasma membrane. The observations document profound changes in Müller cell structural and functional polarity during subretinal scar formation.

The filum terminale of the frog spinal cord is a rather pure glial cell preparation, largely devoid of neuronal elements. gamma-Aminobutyric acid (GABA) is taken up by the frog filum terminale (FT) via a Na+-dependent, ouabain-inhibited, saturable high affinity transport system with a Km of 2.7 x 10(5) M. The rate of the FT GABA uptake is significantly greater than the velocities observed in the spinal cord. In fact, the Vmax increases caudally beyond the level of the last root, and is maximal in the FT per se. beta-Alanine is a competitive inhibitor of the FT high affinity transport system for GABA (Ki 11.1 x 10(-5) M). In addition to GABA, the FT also takes up beta-alanine, glycine, glutamate and aspartate at rates significantly higher than those shown by the spinal cord of the frog. Light and electron microscope level radioautography clearly shows that GABA uptake occurs primarily in the glial cells and also in ependymal cells present in the FT. In that the FT contains few ependymal cells and a large number of glia, it is fair to state that most of the GABA accumulated by the FT reflects the glial transport of this amino acid. Unlike the adult frog, the spinal cord of the tadpole does not show any regional differences in the rate of GABA transport during early development. However, during later developmental stages, the rates of GABA transport increase in the caudal portion of the tadpole cord as compared to the more rostral areas. Close to metamorphosis, the terminal portion of the tadpole cord, which is destined to become the filum terminals of the frog, accumulates GABA at rates not greatly different from those observed in the FT of the adult frog. Therefore, the tadpole spinal cord is a useful preparation in which to study the dynamic properties of normal non-transformed glia as influenced by a changing neuronal population, whereas the frog FT is a unique preparation for the study of some properties of normal glia largely in the absence of neurons.

A 66-year-old man with an 18-year history of cutaneous multicentric reticulohistiocytosis (MRH) developed a chronic destructive symmetrical arthritis and xerostomia. Biopsies of synovium and minor salivary glands established a diagnosis of MRH polyarthritis and lymphocytic infiltrative Sjögren's syndrome, respectively. Anti-Ro(SSA) antibody was present. Hypothyroidism was also identified. This report of Sjögren's syndrome in MRH may enlarge the spectrum of autoimmune diseases associated with MRH.

The neuropeptide proctolin causes a sustained contraction of the opener muscle of the dactyl of the lobster walking leg. This substance acts directly on the muscle at concentrations as low as 10(-10)M. The contraction is dependent on extracellular calcium. Neither a significant depolarization nor a detectable change in the input resistance accompanies the response. No presynaptic action of proctolin is indicated; excitatory and inhibitory junctional potential sizes and the frequency of spontaneous miniature excitatory junctional potentials are unaffected.

The filum terminale, or terminal portion of the spinal cord, was studied in normal adult frogs (Rana pipiens) bu means of light and electron microscopy. Astroglial cells are the predominant elements in this region. The rostral portion of the filum terminale consists mainly of (1) a peripheral dense ring of myelinated and some unmyelinated nerve fibers, and processes of astrobytes terminating at the subpial space; (2) an intermediate zone, in which astrocytes are the main cellular elements in addition to a few degenerated neurons; and (3) a central region where the central canal is lined by dark and light ependymal cells. In the caudal portion of the filum terminale, the amount of neuropil is greatly reduced. This region os formed mainly by astrocytic glial cells and very few neuronal elements. The central canal in the caudal portion is located ventrally and contains a lining consisting almost exclusively of dark ependymal cells.

In this communication we report that four substances, thought to function as neurohormones in Crustacea, all produce long-term changes in the physiological properties of lobster opener muscle preparations. The substances are the amines, octopamine, serotonin and dopamine, and the peptide, proctolin. The actions of these substances are superimposed on the normal synaptic apparatus that utilizes the amino acids GABA and glutamate (probably) as the inhibitory and excitatory neurotransmitter compounds. Serotonin acts on excitatory and inhibitory nerve endings to facilitate transmitter release and directly on muscle fibres to produce a contracture and to induce the appearance of Ca2+ action potentials. The latter two actions of serotonin are shared by proctolin and octopamine as well. Dopamine, on the other hand, relaxes muscle baseline tension. The mechanism of action of these substances at their target site (or sites) has been explored with electrophysiological and biochemical techniques and the results will be presented. In addition preliminary behavioural experiments have been carried out with serotonin and octopamine. These substances produce opposite postures when injected into lobsters. The amines act on central ganglia to produce these effects where they cause a programmed readout of firing of neurones that will produce either a flexed posture (serotonin) or an extended posture (octopamine).

Noradrenaline (25 microM-50 microM) causes an increase in tetanic potentiation and in the augmentation phase of posttetanic potentiation of miniature and plate potential frequency. These effects were observed at both the frog and the rat neuromuscular junctions. The action of noradrenaline on quantal transmitter release depends on the presence of calcium ions in the extracellular medium.

A progressive fibrous myopathy may result from chronic intramuscular drug abuse. This complication may mimic other rheumatic disorders and early recognition may prevent disability. The patient described here presented with fixed flexion and extension contracture of hips and knees, respectively, after abusing meperidine and other agents for 3 years. Soft tissues of thighs and buttocks were "wood hard," EMG showed absence of action potentials in affected muscles, and biopsy revealed extensive replacement of muscle with dense, acellular fibrous tissue. Possible mechanisms are discussed.