Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology

The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features

Nerves and blood vessels in degenerated intervertebral discs are confined to physically disrupted tissue

Nerves and blood vessels are found in the peripheral annulus and endplates of healthy adult intervertebral discs. Degenerative changes can allow these vessels to grow inwards and become associated with discogenic pain, but it is not yet clear how far, and why, they grow in. Previously we have shown that physical disruption of the disc matrix, which is a defining feature of disc degeneration, creates free surfaces which lose proteoglycans and water, and so become physically and chemically conducive to cell migration. We now hypothesise that blood vessels and nerves in degenerated discs are confined to such disrupted tissue. Whole lumbar discs were obtained from 40 patients (aged 37–75 years) undergoing surgery for disc herniation, disc degeneration with spondylolisthesis or adolescent scoliosis (‘non‐degenerated’ controls). Thin (5‐μm) sections were stained with H&E and toluidine blue for semi‐quantitative assessment of blood vessels, fissures and proteoglycan loss. Ten thick (30‐μm) frozen sections from each disc were immunostained for CD31 (an endothelial cell marker), PGP 9.5 and Substance P (general and nociceptive nerve markers, respectively) and examined by confocal microscopy. Volocity image analysis software was used to calculate the cross‐sectional area of each labelled structure, and its distance from the nearest free surface (disc periphery or internal fissure). Results showed that nerves and blood vessels were confined to proteoglycan‐depleted regions of disrupted annulus. The maximum distance of any blood vessel or nerve from the nearest free surface was 888 and 247 μm, respectively. Blood vessels were greater in number, grew deeper, and occupied more area than nerves. The density of labelled blood vessels and nerves increased significantly with Pfirrmann grade of disc degeneration and with local proteoglycan loss. Analysing multiple thick sections with fluorescent markers on a confocal microscope allows reliable detection of thin filamentous structures, even within a dense matrix. We conclude that, in degenerated and herniated discs, blood vessels and nerves are confined to proteoglycan‐depleted regions of disrupted tissue, especially within annulus fissures

Association between changes in lumbar Modic changes and low back symptoms over a two-year period

Background: The association of Modic changes (MC) with low back pain (LBP) is unclear. The purpose of our study was to investigate the associations between the extent of Type 1 (M1) and Type 2 (M2) MC and low back symptoms over a two-year period. Methods: The subjects (n = 64, mean age 43.8 y; 55 [86%] women) were consecutive chronic LBP patients who had M1 or mixed M1/M2 on lumbar spine magnetic resonance imaging (MRI). Size and type of MC on sagittal lumbar MRI and clinical data regarding low back symptoms were recorded at baseline and two-year follow-up. The size (%) of each MC in relation to vertebral size was estimated from sagittal slices (midsagittal and left and right quarter), while proportions of M1 and M2 within the MC were evaluated from three separate slices covering the MC. The extent (%) of M1 and M2 was calculated as a product of the size of MC and the proportions of M1 and M2 within the MC, respectively. Changes in the extent of M1 and M2 were analysed for associations with changes in LBP intensity and the Oswestry disability index (ODI), using linear regression analysis. Results: At baseline, the mean LBP intensity was 6.5 and the mean ODI was 33%. During follow-up, LBP intensity increased in 15 patients and decreased in 41, while ODI increased in 19 patients and decreased in 44. In univariate analyses, change in the extent of M1 associated significantly positively with changes in LBP intensity and ODI (beta 0.26, p = 0.036 and beta 0.30, p = 0.017; respectively), whereas the change in the extent of M2 did not associate with changes in LBP intensity and ODI (beta -0.24, p = 0.054 and beta -0.13, p = 0.306; respectively). After adjustment for age, gender, and size of MC at baseline, change in the extent of M1 remained significantly positively associated with change in ODI (beta 0.53, p = 0.003). Conclusion: Change in the extent of M1 associated positively with changes in low back symptoms.Peer reviewe

Potentially severe drug-drug interactions among older people and associations in assisted living facilities in Finland : a cross-sectional study

Objective: This study aims to assess potentially severe class D drug-drug interactions (DDDIs) in residents 65 years or older in assisted living facilities with the use of a Swedish and Finnish drug-drug interaction database (SFINX). Design: A cross-sectional study of residents in assisted living facilities in Helsinki, Finland. Setting: A total of 1327 residents were assessed in this study. Drugs were classified according to the Anatomical Therapeutic Chemical (ATC) classification system and DDDIs were coded according to the SFINX. Main outcome measures: Prevalence of DDDIs, associated factors and 3-year mortality among residents. Results: Of the participants (mean age was 82.7 years, 78.3% were females), 5.9% (N=78) are at risk for DDDIs, with a total of 86 interactions. Participants with DDDIs had been prescribed a higher number of drugs (10.8 (SD 3.8) vs. 7.9 (SD 3.7), p Conclusions: Of the residents in assisted living, 5.9% were exposed to DDDIs associated with the use of a higher number of drugs. Physicians should be trained to find safer alternatives to drugs associated with DDDIs.Peer reviewe

Validation in the Cross-Cultural Adaptation of the Korean Version of the Oswestry Disability Index

Disability questionnaires are used for clinical assessment, outcome measurement, and research methodology. Any disability measurement must be adapted culturally for comparability of data, when the patients, who are measured, use different languages. This study aimed to conduct cross-cultural adaptation in translating the original (English) version of the Oswestry Disability Index (ODI) into Korean, and then to assess the reliability of the Korean versions of the Oswestry Disability Index (KODI). We used methodology to obtain semantic, idiomatic, experimental, and conceptual equivalences for the process of cross-cultural adaptation. The KODI were tested in 116 patients with chronic low back pain. The internal consistency and reliability for the KODI reached 0.9168 (Cronbach's alpha). The test-retest reliability was assessed with 32 patients (who were not included in the assessment of Cronbach's alpha) over a time interval of 4 days. Test-retest correlation reliability was 0.9332. The entire process and the results of this study were reported to the developer (Dr. Fairbank JC), who appraised the KODI. There is little evidence of differential item functioning in KODI. The results suggest that the KODI is internally consistent and reliable. Therefore, the KODI can be recommended as a low back pain assessment tool in Korea

Test-retest reliability of the Short-Form McGill Pain Questionnaire

Objectives: No previous study has adequately demonstrated the test-retest reliability of the Short-Form McGill Pain Questionnaire, yet it is increasingly being used as a measure of pain. This study evaluates the test-retest reliability in patients with osteoarthritis. Methods: A prospective, observational cohort study was undertaken using serial evaluation of 57 patients at 2 time points. A sample of patients awaiting primary hip or knee joint replacement surgery were recruited in clinic or via mail (mean age 64.8 years). Short-Form McGill Pain Questionnaires were delivered by mail 5 days apart, and a supplementary questionnaire was completed on the second occasion to explore if the patients’ pain report had remained stable. Results: The intraclass correlation coefficient was used as an estimate of reliability. For the total, sensory, affective, and average pain scores, high intra-class correlations were demonstrated (0.96, 0.95, 0.88, and 0.89, respectively). The current pain component demonstrated a lower intraclass correlation of 0.75. The coefficient of repeatability was calculated as an estimation of the minimum metrically detectable change. The coefficients of repeatability for the total, sensory, affective, average, and current pain components were 5.2, 4.5, 2.8, 1.4 cm, and 1.4, respectively. Discussion: Problems of adequate completion of the Short-Form McGill Pain Questionnaire were highlighted in this sample, and supervision via telephone contact was required. Patients recruited in clinic who had practiced completing the Short-Form McGill Pain Questionnaire demonstrated fewer errors than those recruited by mail. The Short-Form McGill Pain Questionnaire was demonstrated to be a highly reliable measure of pain. These results should not be generalized to a more elderly population, as increasing age was correlated with greater variability of the sensory component scores.</p

Diagnostic Value of Lumbar Facet Joint Injection: A Prospective Triple Cross-Over Study

The diagnosis “lumbar facet syndrome” is common and often indicates severe lumbar spine surgery procedures. It is doubtful whether a painful facet joint (FJ) can be identified by a single FJ block. The aim of this study was to clarify the validity of a single and placebo controlled bilateral FJ blocks using local anesthetics. A prospective single blinded triple cross-over study was performed. 60 patients (31 f, 29 m, mean age 53.2 yrs (22–73)) with chronic low back pain (mean pain persistance 31 months, 6 months of conservative treatment without success) admitted to a local orthopaedic department for surgical or conservative therapy of chronic LBP, were included in the study. Effect on pain reduction (10 point rating scale) was measured. The 60 subjects were divided into six groups with three defined sequences of fluoroscopically guided bilateral monosegmental lumbar FJ test injections in “oblique needle” technique: verum-(local anaesthetic-), placebo-(sodium chloride-) and sham-injection. Carry-over and periodic effects were evaluated and a descriptive and statistical analysis regarding the effectiveness, difference and equality of the FJ injections and the different responses was performed. The results show a high rate of non-response, which documents the lack of reliable and valid predictors for a positive response towards FJ blocks. There was a high rate of placebo reactions noted, including subjects who previously or later reacted positively to verum injections. Equivalence was shown among verum vs. placebo and partly vs. sham also. With regard to test validity criteria, a single intraarticular FJ block with local anesthetics is not useful to detect the pain-responsible FJ and therefore is no valid and reliable diagostic tool to specify indication of lumbar spine surgery. Comparative FJ blocks with local anesthetics and placebo-controls have to be interpretated carefully also, because they solely give no proper diagnosis on FJ being main pain generator

Retro-trochanteric sciatica-like pain: current concept

The aim of this manuscript is to review the current knowledge in terms of retro-trochanteric pain syndrome, make recommendations for diagnosis and differential diagnosis and offer suggestions for treatment options. The terminology in the literature is confusing and these symptoms can be referred to as ‘greater trochanteric pain syndrome’, ‘trochanteric bursitis’ and ‘trochanteritis’, among other denominations. The authors focus on a special type of sciatica, i.e. retro-trochanteric pain radiating down to the lower extremity. The impact of different radiographic assessments is discussed. The authors recommend excluding pathology in the spine and pelvic area before following their suggested treatment algorithm for sciatica-like retro-trochanteric pain. Level of evidence II

The provocative lumbar facet joint

Low back pain is the most common pain symptom experienced by American adults and is the second most common reason for primary care physician visits. There are many structures in the lumbar spine that can serve as pain generators and often the etiology of low back pain is multifactorial. However, the facet joint has been increasingly recognized as an important cause of low back pain. Facet joint pain can be diagnosed with local anesthetic blocks of the medial branches or of the facet joints themselves. Subsequent radiofrequency lesioning of the medial branches can provide more long-term pain relief. Despite some of the pitfalls associated with facet joint blocks, they have been shown to be valid, safe, and reliable as a diagnostic tool. Medial branch denervation has shown some promise for the sustained control of lumbar facet joint-mediated pain, but at this time, there is insufficient evidence that it is a wholly efficacious treatment option. Developing a universal algorithm for evaluating facet joint-mediated pain and standard procedural techniques may facilitate the performance of larger outcome studies. This review article provides an overview of the anatomy, pathophysiology, diagnosis, and treatment of facet joint-mediated pain