Chronic neuropathic pain in patients with spinal cord injury. What is the efficacy of regional interventions? Sympathetic blocks,nerve blocks and intrathecal drugs

ObjectiveTo elaborate recommendations regarding neuropathic pain management in spinal cord injury patients. The goal was to evaluate the efficacy of local anesthetic therapeutics including intrathecal or epidural treatments, sympathetic and nerve blocks.MethodThe methodology, proposed by the French Society of Physical Medicine and Rehabilitation (SOFMER), includes a systematic revue of the literature, the gathering of information regarding current clinical practice and a validation by a multidisciplinary panel of experts.ResultsThe results of the literature review do not validate the efficacy of clonidine, baclofen, morphine or lidocaine administered via intrathecal (IT) drug delivery or epidural injections on neuropathic pain in spinal cord injury patients. One reason could be the methodological limitations of the studies. Another reason could be that in most cases the evaluation is done after one single dose injection, thus preventing the authors from assessing the efficacy of the treatments on the long-term. Various clinical practices experiences lead us into thinking that there is, in some cases, a real efficacy for IT baclofen delivery, but this still remains to be properly defined in terms of patients characteristics and type of neuropathic pain. Regarding anesthetic nerve root blocks and sympathetic blocs, no element is available to validate the efficacy of these techniques.ConclusionThere is not a sufficient level of proof to recommend using IT or epidural drug delivery for treating neuropathic pain. However, according to the clinical practices data reviewed, we can suggest to conduct further studies on the impact of IT baclofen delivery that seems to have a pain-relieving impact in some situations. It would be interesting to identify the subgroups of patients that could benefit from this treatment.     

Synergistic Effect between Colistin and Bacteriocins in Controlling Gram-Negative Pathogens and Their Potential To Reduce Antibiotic Toxicity in Mammalian Epithelial Cells

Pathogens resistant to most conventional antibiotics are a harbinger of the need to discover novel antimicrobials and anti-infective agents and develop innovative strategies to combat them. The aim of this study was to assess the in vitro activity of colistin alone or in combination with two bacteriocins, nisin A and pediocin PA-1/AcH, against Salmonella choleraesuis ATCC 14028, Pseudomonas aeruginosa ATCC 27853, Yersinia enterocolitica ATCC 9610, and Escherichia coli ATCC 35150 (O157:H7). The strain most sensitive to colistin was enterohemorrhagic E. coli O157:H7, which was inhibited at a concentration of about 0.12 μg/ml. When nisin A (1.70 μg/ml) or pediocin PA-1/AcH (1.56 μg/ml) was combined with colistin, the concentrations required to inhibit E. coli O157:H7 were 0.01 and 0.03 μg/ml, respectively. The in vitro antigenotoxic effect of colistin was determined by using the comet assay method to measure the level of DNA damage in freshly isolated human peripheral blood leukocytes (PBLs) incubated with colistin for 1 h at 37°C. Changes in the tail extents of PBLs of about 69.29 ± 0.08 μm were observed at a final colistin concentration of about 550 ng/ml. Besides the synergistic effect, the combination of colistin (1 mg/ml) and nisin (2 mg/ml) permitted us to re-evaluate the toxic effect of colistin on Vero (monkey kidney epithelial) cells.     

Novel mutations in the PRX and the MTMR2 genes are responsible for unusual Charcot-Marie-Tooth disease phenotypes

Autosomal recessive Charcot-Marie-Tooth diseases, relatively common in Algeria due to high prevalence of consanguineous marriages, are clinically and genetically heterogeneous. We report on two consanguineous families with demyelinating autosomal recessive Charcot-Marie-Tooth disease (CMT4) associated with novel homozygous mutations in the MTMR2 gene, c.331dupA (p.Arg111LysfsX24) and PRX gene, c.1090C>T (p.Arg364X) respectively, and peculiar clinical phenotypes. The three patients with MTMR2 mutations (CMT4B1 family) had a typical phenotype of severe early onset motor and sensory neuropathy with typical focally folded myelin on nerve biopsy. Associated clinical features included vocal cord paresis, prominent chest deformities and claw hands. Contrasting with the classical presentation of CMT4F (early-onset Dejerine-Sottas phenotype), the four patients with PRX mutations (CMT4F family) had essentially a late age of onset and a protracted and relatively benign evolution, although they presented marked spine deformities. These observations broaden the spectrum of clinical phenotypes associated with these two CMT4 forms.     

Identification and induction of cytochrome P450s involved in the metabolism of flavone-8-acetic acid in mice

The metabolism of flavone-8-acetic acid (FAA) has been hypothesized to be partly responsible for its potent anticancer activity in mice. The purpose of this study was to identify the mouse enzymes involved in FAA Phase I metabolism and evaluate their possible induction in vivo by FAA. Mouse microsomes metabolized FAA into 6 metabolites: 3',4'-dihydrodiol-FAA, 5,6-epoxy-FAA, 4'-OH-FAA, 3'-OH-FAA, 3',4'-epoxy-FAA and 6-OH-FAA. Using Cyp-specific inhibitors (furafylline, Cyp1a2; α-naphthoflavone, Cyp1b1; tranylcypromine, Cyp2b9; quercetin, Cyp2c29; quinidine, 2d9; diethyldithiocarbamate, Cyp2e1; ketoconazole, Cyp3a11), the formation of 5,6-epoxy-FAA was mainly attributed to Cyps 1a2, 1b1, 2b9, 2c29 and 2e1, whereas the 3',4'-epoxy-FAA was formed by Cyps 2b9 and 3a11. The 4'-OH-FAA was generated by Cyps 1a2, 1b1, 2b9 and 2e1, and the 6-OH-FAA was formed by Cyps 1b1 and 2c9. Using the epoxide scavenger N-acetyl cysteine, 4'-OH-FAA, 3'-OH-FAA and 6-OH-FAA were shown to derive partly from non enzymatic isomerisation of their corresponding epoxides. The specific epoxide hydrolase inhibitor elaidamide allowed the confirmation that 3',4'-dihydrodiol-FAA was formed via the epoxide hydrolase. FAA treatment in vivo in mice led to a significant increase in the hepatic expression of Cyp1a2 (1.9-fold), 2e1 (2.1-fold), 2b10 (3.2-fold), 2d9 (2.3-fold) and 3a11 (2.2-fold), as evaluated by qRT-PCR. In conclusion, several Cyps were shown to be involved in FAA metabolism, particularly Cyps 3a11 and 2b9 which were responsible for the formation of the principal metabolites (5,6-epoxy-FAA, 3',4'-epoxy-FAA), and that FAA could induce the expression of several Cyps after in vivo administration. The possible implication of these enzymes in the in vivo anticancer activity of FAA in mice is discussed.     

Relevance of botulinum toxin injection and nerve block of rectus femoris to kinematic and functional parameters of stiff knee gait in hemiplegic adults

Stiff knee gait (SKG) is common in hemiplegic patients. The main focus of treatment is rectus femoris (RF) spasticity. The aims of this study were to evaluate the effect of botulinum toxin injection (BTI) in the RF muscle on peak knee flexion during swing phase and its quantitative and functional impact on gait. We also wished to evaluate the correlation between the effects of nerve block and BTI on peak knee flexion. 10 adult hemiplegic subjects (>6 months post stroke or traumatic brain injury) with SKG and inappropriate RF EMG activity during mid-swing phase were included. 3D gait analysis, clinical and functional assessments (Timed Up and Go test, 10 m walk test, 6 min walk test and the time taken to ascend and descend a flight of stairs) were performed initially, 30 min after anaesthetic block of the RF nerve and one month post BTI. After BTI, there was a significant increase in knee flexion (8 degrees average) and a tendency towards improvement in gait and functional parameters. The effect of the nerve block on peak knee flexion was significantly correlated with the effect of BTI (11 degrees average increase in peak knee flexion after nerve block). We challenge the relevance of RF nerve blocks in this population when EMG and kinematic data are available. Our results indicate that BTI is an effective treatment for SKG in adult hemiplegic subjects, with a significant increase in peak knee flexion, no reduction in hip flexion and a tendency towards functional improvements.