The prevalence and cost of chronic pain is a major physical and mental health care problem in the United States today. As a result, there has been a recent explosion of research on chronic pain, with significant advances in better understanding its etiology, assessment, and treatment. The purpose of the present article is to provide a review of the most noteworthy developments in the field. The biopsychosocial model is now widely accepted as the most heuristic approach to chronic pain. With this model in mind, a review of the basic neuroscience processes of pain (the bio part of biopsychosocial), as well as the psychosocial factors, is presented. This spans research on how psychological and social factors can interact with brain processes to influence health and illness as well as on the development of new technologies, such as brain imaging, that provide new insights into brain-pain mechanisms.

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The Biopsychosocial Approach to Chronic Pain: Scientific Advances and Future Directions

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that selectively affects optic nerves and spinal cord. It is considered a severe variant of multiple sclerosis (MS), and frequently is misdiagnosed as MS, but prognosis and optimal treatments differ. A serum immunoglobulin G autoantibody (NMO-IgG) serves as a specific marker for NMO. Here we show that NMO-IgG binds selectively to the aquaporin-4 water channel, a component of the dystroglycan protein complex located in astrocytic foot processes at the blood-brain barrier. NMO may represent the first example of a novel class of autoimmune channelopathy.

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IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

https://www2.mrc-lmb.cam.ac.uk/groups/nu/pdf/jmb05.pdf

Refined Structure of the Nicotinic Acetylcholine Receptor at 4A Resolution

The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3. This region contains the gene SCN9A, encoding the alpha-subunit of the voltage-gated sodium channel, Na(v)1.7, which is strongly expressed in nociceptive neurons. Sequence analysis of SCN9A in affected individuals revealed three distinct homozygous nonsense mutations (S459X, I767X and W897X). We show that these mutations cause loss of function of Na(v)1.7 by co-expression of wild-type or mutant human Na(v)1.7 with sodium channel beta(1) and beta(2) subunits in HEK293 cells. In cells expressing mutant Na(v)1.7, the currents were no greater than background. Our data suggest that SCN9A is an essential and non-redundant requirement for nociception in humans. These findings should stimulate the search for novel analgesics that selectively target this sodium channel subunit.

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An SCN9A channelopathy causes congenital inability to experience pain

THIS report gives the neurologic, genetic, and electrophysiologic findings of a prospective study of kinships with different hereditary neurologic disorders having symmetric neurogenic weakness and atrophy as an early- and often major manifestation. The study was undertaken to obtain more reliable information about the natural history of these disorders, to test the usefulness of electro physiologic studies in distinguishing affected from nonaffected persons, to compare the results of nerve biopsies from representative affected persons with these disorders, and to develop a more meaningful classification. In this, the first of two articles on the subject, the results of neurologic, genetic, and electrophysiologic studies of 67 persons with hypertrophic neuropathy of the Charcot-Marie-Tooth type, five persons with hypertrophic neuropathy of the Dejerine-Sottas type, and 150 unaffected relatives are given. We also wished to determine whether these syndromes were phenotypic variations of one or several diseases or were separate entities on the

Lower Motor and Primary Sensory Neuron Diseases With Peroneal Muscular Atrophy: I. Neurologic, Genetic, and Electrophysiologic Findings in Hereditary Polyneuropathies

Background Voltage-gated calcium channels in small-cell lung carcinomas may initiate autoimmunity in the paraneoplastic neuromuscular disorder Lambert–Eaton syndrome. The calcium-channel subtype that is responsible is not known. Methods We compared the effects of antagonists of L-type, N-type, and P/Q-type neuronal calcium channels on the depolarization-dependent influx of calcium-45 in cultured carcinoma cells. Serum samples from patients with various disorders were tested for reactivity with P/Q-type channels solubilized from carcinoma and cerebellar membranes and N-type channels from cerebral cortex. Results P/Q-type calcium-channel antagonists were the most potent inhibitors of depolarization-induced 45Ca influx in cultured small-cell carcinoma cell lines. Anti–P/Q-type calcium-channel antibodies were found in serum from all 32 patients with the Lambert–Eaton syndrome and a diagnosis of cancer and in 91 percent of the 33 patients with the Lambert–Eaton syndrome without cancer. Anti–N-type calcium-chan...

https://www.nejm.org/doi/pdf/10.1056/NEJM199506013322203

Calcium-Channel Antibodies in the Lambert–Eaton Syndrome and Other Paraneoplastic Syndromes

THE companion paper 1 on this topic considered the inherited hypertrophic neuropathies in which peroneal muscle weakness and atrophy is prominent. In those disorders, a symmetric neurogenic weakness and atrophy is an early and prominent feature, conduction velocities of peripheral nerves are markedly reduced, and histologic studies reveal abnormalities of Schwann cells and of myelinization. This paper considers cases of neuronal degeneration in which peroneal muscle weakness and atrophy is prominent. In this group of cases, conduction velocities of nerves are either normal or slightly low and nerve biopsies show no evidence of segmental demyelinization or hypertrophy of nerve. In some of these cases there is probably selective degeneration of anterior horn and dorsal root ganglion cells with degeneration of axons; in other cases the site of degeneration of the neuron is less well understood—a metabolic disorder of the neuron may be the cause of degeneration of nerve terminals

https://jamanetwork.com/journals/NEUR/articlepdf/568126/archneur_18_6_003.pdf

Lower Motor and Primary Sensory Neuron Diseases With Peroneal Muscular Atrophy: II. Neurologic, Genetic, and Electrophysiologic Findings in Various Neuronal Degenerations

Although there is strong evidence that myasthenia gravis (MG) is caused by an autoimmune reaction to the nicotinic postsynaptic acetylcholine receptor (AChR) protein, immune complexes have never been directly demonstrated at the end-plate by immunocyto-chemistry or immunoelectron microscopy. Staphylococcal protein A (which binds to the Fc region of human IgG subclasses 1, 2, and 4) and rabbit anti-human C3 conjugated with peroxidase were used for the ultrastructural (5 patients) and light microscopic (12 patients) localization of IgG and C3, respectively, at MG end-plates. Both IgG and C3 were localized on segments of the postsynaptic membrance and fragments of degenerating junctional folds in the synaptic space. In nonmyasthenic control patients no immune complexes were evident at the end-plate. As judged by morphometric analysis of electron micrographs, the immune complexes were more abundant in the less severely affected MG patients than in the more severely affected ones. A linear correlation was demonstrated between the length of the postsynaptic membrance binding immune complexes and the amplitude of the miniature end-plate potential. The less intense reaction for immune complexes in the more severely affected MG patients can be attributed to the smaller quantity of AChR remaining at their end-plates. The findings provide unambiguous evidence for a destructive auto-immune reaction involving the postsynaptic membrance in MG. Immunopharmacologic blockade of AChR and IgG-induced modulation of AChR may also contribute to the AChR deficiency at the MG end-plates.

Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations.

Intensive evaluation of 205 cases of undiagnosed neuropathy in a center with special approaches and facilities permitted classification of 76% of the patients. Inherited disorders accounted for 42% of the series, 21% of the patients were shown to have inflammatory-demyelinating polyradiculoneuropathy, and 13% had neuropathies associated with other disorders. A considerable improvement in diagnosis was possible from evaluation of the kin of the patients with undiagnosed neuropathy. Analysis of the frequency and type of various sensory symptoms also was helpful in distinguishing between acquired and inherited neuropathies.

Edward H. Lambert

Papers

Lower Motor and Primary Sensory Neuron Diseases With Peroneal Muscular Atrophy: I. Neurologic, Genetic, and Electrophysiologic Findings in Hereditary Polyneuropathies

Calcium-Channel Antibodies in the Lambert–Eaton Syndrome and Other Paraneoplastic Syndromes

Lower Motor and Primary Sensory Neuron Diseases With Peroneal Muscular Atrophy: II. Neurologic, Genetic, and Electrophysiologic Findings in Various Neuronal Degenerations

Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations.

Intensive evaluation of referred unclassified neuropathies yields improved diagnosis