Involvement of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex of normal rats and rats with mononeuropathy.

The present study was performed to explore the role of galanin and galanin receptor 2 in nociceptive modulation in anterior cingulate cortex (ACC) of normal rats and rats with mononeuropathy. Intra-ACC injection of galanin induced significant increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulations in both normal rats and rats with mononeuropathy, the increased HWLs were attenuated significantly by intra-ACC injection of galanin receptor 2 antagonist M871, indicating an involvement of galanin receptor 2 in nociceptive modulation in ACC. Interestingly, the galanin-induced HWL was significant higher in rats with mononeuropathy than that in normal rats tested by Randall Selitto test. Furthermore, both the galanin mRNA expression and galanin content increased significantly in ACC in rats with mononeuropathy than that in normal rats. Moreover, both the mRNA levels of galanin receptor 2 and the content of galanin receptor 2 in ACC increased significantly in rats with mononeuropathy than that in normal rats. These results found that galanin induced antinociception in ACC in both normal rats and rats with mononeuropathy. And there may be plastic changes in the expression of galanin and galanin receptor 2 in rats with mononeuropathy, as well as in the galanin-induced antinociception.

Mononeuritis multiplex: association with infectious condition and familial background in a tropical environment: a case report.

Mononeuritis multiplex is characterized by an asymmetric pattern with affection of the peripheral nervous system; this form of polyneuropathy is often seen in non-systemic vasculitis. We present a case of multiplex neuropathy in a patient with histologicaly verified Hailey-Hailey disease. With the exception of this comorbidity--in its characteristic form presenting additionally with a superinfected subdermal node--we did not find any other possible etiologic factor possibly causative of multiplex neuritis. The diagnosis was confirmed by electrophysiological testing. To our knowledge, this is the first case report indicating a possible relationship between Hailey-Hailey disease and multiplex neuritis. There exists only one related study in the literature, which was conducted in Columbia--our patient's home country. This study delineates a clinically similar dermal disease (pemphigus foliaceus) in patients from rural Colombia (El Bagre). The authors detected anti-neuronal antibodies which were interpreted to be responsible for the pathognomonic burning sensations.

Results of a haplotype-based GWAS for recurrent laryngeal neuropathy in the horse.

Recurrent laryngeal neuropathy (RLN) is a major upper-airway disease of horses that causes abnormal respiratory noise during exercise and can impair performance. Etiopathogenesis remains unclear but genetic factors have been suspected for many decades. The objective of this study was to identify risk loci associated with RLN. To that end we genotyped 234 cases (196 Warmbloods, 20 Trotters, 14 Thoroughbreds, and 4 Draft horses), 228 breed-matched controls, and 69 parents with the Illumina Equine SNP50 BeadChip. Using these data, we quantified population structure and performed single-marker and haplotype-based association studies, as well as family-based linkage analyses. We accounted for population stratification by modeling a random polygenic background effect with covariance structure estimated from genome-wide SNP data. Using the haplotype-based approach, we identified two genome-wide suggestive loci in Warmbloods, respectively on chromosomes 21 (p = 1.62 × 10(-6)) and 31 (p = 1.69 × 10(-5)). The two signals were driven by the enrichment of a "protective" haplotype in controls compared to cases.

Primary amyloidosis presenting as upper limb multiple mononeuropathies.

Peripheral neuropathy in primary (AL) amyloidosis is usually lower-limb predominant, length-dependent, symmetrical, and affects small (pain and autonomic) fibers, as much or more than large fibers. We report a patient with stepwise progressive, multiple upper limb mononeuropathies that were due to nerve biopsy-proven primary amyloidosis (lambda light chain), with no systemic or autonomic features. Recognition that light chain amyloidosis may be the cause of a multiple mononeuropathy pattern adds to the differential diagnosis of this clinical phenotype.

Intrathecal coelectrotransfer of a tetracycline-inducible, three-plasmid-based system to achieve tightly regulated antinociceptive gene therapy for mononeuropathic rats.

For optimal use of antinociceptive gene therapy, it may be important to have extrinsic control of the expression of the transfected gene. To achieve this goal, we used a tetracycline-inducible system (Tet-On) composed of three plasmids coding for beta-endorphin, the tetracycline transcriptional activator rtTA, and the silencer tTS. The regulation of beta-endorphin expression was first assessed in cultures of dorsal root ganglion neurons. The three plasmids were then electrotransfected into the spinal cord of mononeuropathic rats and the analgesic potential of this therapy in vivo was evaluated by thermal-withdrawal latency and the mechanical-withdrawal threshold. Intraperitoneal injections of doxycycline were made to evaluate the possibility of exogenous upregulation of transfected beta-endorphin gene expression in vivo. The levels of beta-endorphin were analyzed by intrathecal microdialysis and radioimmunoassay. We found that, after doxycycline administration, the expression of beta-endorphin was rapid, stable, and tightly regulated (low background and high induction level) both in vitro and in vivo. The beta-endorphin protein was secreted into cerebrospinal fluid at a peak level of 53 pmol/L in dialysate, which was sufficient to inhibit neuropathic pain. In conclusion, tightly controlled expression of beta-endorphin can be obtained following intrathecal electrotransfer of a tetracycline-inducible, three-plasmid-based system, and doxycycline-dependent beta-endorphin protein expression in this system alleviates sciatic nerve constriction-induced limb pain.

Transthyretin amyloidosis presenting with multifocal demyelinating mononeuropathies.

We describe a patient with transthyretin amyloidosis who presented with multifocal mononeuropathies with features of demyelination on nerve conduction studies, a constellation of findings not previously described in amyloid polyneuropathy. Genetic testing revealed a valine122isoleucine mutation in the coding region of the transthyretin gene, a mutation that generally presents with late-onset cardiac amyloidosis. Our patient was also unusual in that she was 34 years old at the time of presentation and had no cardiac involvement.

Hereditary neuropathy with liability to pressure palsies in infancy.

Hereditary neuropathy with liability to pressure palsies is an autosomal-dominant disorder, classically characterized by recurrent mononeuropathies, associated with a deletion at 17p11.2, encompassing the peripheral myelin protein 22 gene. The typical clinical episodes of pressure palsy are usually noted for the first time during the 2nd or 3rd decade of life. We found only few reports in prepubertal children. We report a case of a 7.5-year-old child with muscle weakness and severe hypotonia associated with developmental gross motor delay. We suspect that bilateral peroneal nerve palsies after birth were the first episode of pressure palsy. Nerve conduction studies demonstrated slightly prolonged distal latencies with normal conduction velocity. Typical features of hereditary neuropathy with liability to pressure palsies with recurrent mononeuropathies were found in the father. DNA analysis revealed 1.5-Mb deletion at 17p11.2 in both father and child. To the best of our knowledge, this patient is one of the youngest ever found with this disease.