Abnormal LDIflare but Normal Quantitative Sensory Testing and Dermal Nerve Fiber Density in Patients with Painful Diabetic Neuropathy

OBJECTIVE—Abnormal small nerve fiber function may be an early feature of diabetic neuropathy and may also underlie painful symptoms. Methods for assessing small-fiber damage include quantitative sensory testing (QST) and determining intraepidermal nerve fiber density. We recently described a reproducible physiological technique, the LDIflare, which assesses small-fiber function and thus may reflect early dysfunction before structural damage. The value of this technique in painful neuropathy was assessed by comparing it with QST and dermal nerve fiber density (NFD)

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Tracking azimuthons in nonlocal nonlinear media

We study the formation of azimuthons, i.e., rotating spatial solitons, in media with nonlocal focusing nonlinearity. We show that whole families of these solutions can be found by considering internal modes of classical non-rotating stationary solutions, namely vortex solitons. This offers an exhaustive method to identify azimuthons in a given nonlocal medium. We demonstrate formation of azimuthons of different vorticities and explain their properties by considering the strongly nonlocal limit of accessible solitons.Comment: 11 pages, 7 figure

Vacuolar myopathy in a dog resembling human sporadic inclusion body myositis

Sporadic inclusion body myositis (sIBM) is the most common myopathy in people over the age of 50 years. While immune-mediated inflammatory myopathies are well documented in dogs, sIBM has not been described. An 11-year-old dog with chronic and progressive neuromuscular dysfunction was evaluated for evidence of sIBM using current pathologic, immunohistochemical and electron microscopic diagnostic criteria. Vacuoles and congophilic intracellular inclusions were identified in cryostat sections of multiple muscle biopsies and immunostained with antibodies against amyloid-β peptide, amyloid-β precursor protein, and proteosome 20S of the ubiquitin–proteosome system. Cellular infiltration and increased expression of MHC Class I antigen were observed. Cytoplasmic filamentous inclusions, membranous structures, and myeloid bodies were identified ultrastructurally. These observations constitute the first evidence that both the inflammatory and degenerative features of human sIBM can occur in a non-human species

Painful and painless mutations of SCN9A and SCN11A voltage-gated sodium channels

Chronic pain is a global problem affecting up to 20% of the world’s population and has a significant economic, social and personal cost to society. Sensory neurons of the dorsal root ganglia (DRG) detect noxious stimuli and transmit this sensory information to regions of the central nervous system (CNS) where activity is perceived as pain. DRG neurons express multiple voltage-gated sodium channels that underlie their excitability. Research over the last 20 years has provided valuable insights into the critical roles that two channels, NaV1.7 and NaV1.9, play in pain signalling in man. Gain of function mutations in NaV1.7 cause painful conditions while loss of function mutations cause complete insensitivity to pain. Only gain of function mutations have been reported for NaV1.9. However, while most NaV1.9 mutations lead to painful conditions, a few are reported to cause insensitivity to pain. The critical roles these channels play in pain along with their low expression in the CNS and heart muscle suggest they are valid targets for novel analgesic drugs

Electrical stimulation of the posterior tibial nerve reduces neuropathic pain in patients with polyneuropathy

Ron Dabby,1,2 Menachem Sadeh,1,2 Ilan Goldberg,1,2 Vitaly Finkelshtein1,2 1Department of Neurology, Wolfson Medical Center, Holon, 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Abstract: Peripheral neuropathic pain (PNP) is caused by neuronal damage to the peripheral nervous system and usually affects the distal extremities. This open-label study examined the effect of short-term peripheral nerve stimulation (PNS) on individuals with PNP due to polyneuropathy. A total of 12 patients (mean age, 63.0 ± 10.0 years, 41.7% male) with daily bilateral PNP for at least 6 months (mean duration, 7.4 ± 7.8 years) received a total of six direct electrical stimulation therapies to the posterior tibial nerve at 3–4-day intervals. Eight patients completed the study and were included in the efficacy analysis. The average pain at baseline was 36.6 ± 3.80 estimated by the Short-Form McGill Pain Questionnaire. After the last stimulation, pain was significantly reduced by 85.5% to 4.88 ± 3.1 (p = 0.008). Six patients (75%) had over 50% decrease in pain after the first stimulation therapy and 99.2% after the final stimulation therapy. The patients also reported statistically significant decreases in pain level (measured by visual analog scale), ranging from 54.85% to 87.50% after each of the stimulations as compared to the pain experienced prior to the stimulations. The procedure was safe without any serious adverse events. PNS has demonstrated excellent efficacy and improvement of PNP symptoms. Further studies in larger patient populations are warranted. Keywords: peripheral nerve stimulation, posterior tibial nerve stimulation, peripheral neuropathic pain, quality of lif

Molecular genetic study of myophosphorylase deficiency (McArdle's disease) in two Yemenite-Jewish families

Using direct sequencing and restriction fragment length polymorphism analysis, we identified two novel mutations in two unrelated Yemenite-Jewish families with typical symptoms of McArdle's disease. In one family, both father and daughter were affected, an example of pseudo-dominant transmission. The daughter was a compound heterozygote for a new nonsense mutation (R207X) and a new missense mutation (R602Q) while her father was homozygous for the R207X mutation. The mother carried only the R602Q mutation and was an asymptomatic heterozygote. In the second family, the only affected member was homozygous for the R207X mutation. This first molecular genetic study of McArdle's disease in Yemenite-Jewish patients expands the already remarkable genetic heterogeneity of McArdle's disease and suggests the existence of ethnic or private mutations within this group. (C) 2002 Elsevier Science B.V. All rights reserved