Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

An out-of-frame cytochrome b gene deletion from a patient with Parkinsonism is associated with impaired complex III assembly and an increase in free radical production

We have isolated transmitochondrial cybrids containing a mitochondrial DNA cytochrome b 4–base pair deletion previously identified in a patient with parkinsonism. This presentation is in contrast to that of most patients with cytochrome b mutations, who present with exercise intolerance. Clones containing different levels of the cytochrome b 4–base pair deletion showed that high levels of the mutation were associated with a respiratory deficiency and a specific complex III defect. Newly synthesized full‐length cytochrome b was undetectable by metabolic labeling of mutant cells, and these cells were unable to grow in media that restricts proliferation of cells with defective oxidative phosphorylation. Steady state levels of some subunits previously found to be in close association with cytochrome b by crystallography and biochemical analysis (ie, Rieske [2Fe‐2S] protein and subunit VI) were drastically reduced in clones containing high levels of the mutation, whereas the reduction in the core‐1 subunit was milder. The absence of cytochrome b and complex III activity was also associated with increased hydrogen peroxide production. These findings, together with the variable tissue distribution of pathogenic mitochondrial DNA molecules, provide clues to the heterogeneous phenotypes associated with mitochondrial DNA mutations and establish a link between different forms of parkinsonism and oxidative phosphorylation defects. Ann Neurol 2000;48:774–78