BackgroundAlthough the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP), there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP.MethodsIn each of 107 human subjects (60 with LBP and 47 without LBP), parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound.ResultsThere were no significant differences in age, sex, body mass index (BMI) or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p < 0.01 and p < 0.001 respectively).ConclusionThis is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

Hrdlicka ([1914] Smithson. Inst. Misc. Collect. 61:1-69) reported that pre-Columbian skeletal material from the coastal lowland Andean region exhibited a high frequency of porotic hyperostosis, a pathological condition of bone that generally is thought to indicate childhood anemia. While subsequent studies tended to reinforce this conclusion, factors implicated in the condition have yet to be fully explored in the region as a whole. This study explores regional and intravalley variation as one step in establishing biocultural variables that increase the apparent risk of childhood anemia. The study sample includes 1,465 individuals: 512 from Peruvian collections housed at the Field Museum of Natural History, and 953 from systematically excavated contexts from Moquegua, Peru. Environmental stressors, such as parasites and disease, rather than specific dietary practices were found to be more likely associated with childhood anemia in these coastal Andean samples. The study supports cribra orbitalia as an earlier expression of porotic hyperostosis and suggests that porotic hyperostosis, as recorded here, cannot be easily dismissed as a result of cranial shape modification. No clear temporal patterns were observed. Finally, the study establishes that comparing data for children and adults can reveal the relative association between childhood anemia and mortality. Childhood mortality associated with anemia was elevated where the presence of tuberculosis or tuberculosis-like conditions was more common and the presence of water-borne pathogens was negligible. In contrast, those buried at lower altitudes, closer to the coast, and consuming mainly marine resources were less likely to die in childhood with anemia than in the other contexts studied.

Transforming growth factor beta 1 (TGF-β1) plays a key role in connective tissue remodeling, scarring, and fibrosis. The effects of mechanical forces on TGF-β1 and collagen deposition are not well understood. We tested the hypothesis that brief (10 min) static tissue stretch attenuates TGF-β1-mediated new collagen deposition in response to injury. We used two different models: (1) an ex vivo model in which excised mouse subcutaneous tissue (N = 44 animals) was kept in organ culture for 4 days and either stretched (20% strain for 10 min 1 day after excision) or not stretched; culture media was assayed by ELISA for TGF-β1; (2) an in vivo model in which mice (N = 22 animals) underwent unilateral subcutaneous microsurgical injury on the back, then were randomized to stretch (20-30% strain for 10 min twice a day for 7 days) or no stretch; subcutaneous tissues of the back were immunohistochemically stained for Type-1 procollagen. In the ex vivo model, TGF-β1 protein was lower in stretched versus non-stretched tissue (repeated measures ANOVA, P < 0.01). In the in vivo model, microinjury resulted in a significant increase in Type-1 procollagen in the absence of stretch (P < 0.001), but not in the presence of stretch (P = 0.21). Thus, brief tissue stretch attenuated the increase in both soluble TGF-β1 (ex vivo) and Type-1 procollagen (in vivo) following tissue injury. These results have potential relevance to the mechanisms of treatments applying brief mechanical stretch to tissues (e.g., physical therapy, respiratory therapy, mechanical ventilation, massage, yoga, acupuncture).Transforming growth factor β1 (TGF-β1) is well-established as one of the key cytokines regulating the response of fibroblasts to injury, as well as the pathological production of fibrosis (Barnard et al., 1990;Sporn and Roberts, 1990;Leask and Abraham, 2004). Tissue injury is known to cause auto-induction of TGF-β1 protein production and secretion (Van Obberghen-Schilling et al., 1988;Morgan et al., 2000). Elevated extracellular levels of TGF-β1 have a major impact on extracellular matrix composition by causing autocrine and paracrine activation of fibroblast cell surface receptors, leading to increased synthesis of collagens, elastin, proteoglycans, fibronectin, and tenascin (Balza et al., 1988;Bassols and Massague, 1988;Kahari et al., 1992;Cutroneo, 2003). In vivo, connective tissue remodeling is not limited to tissue injury, but also occurs in response to changing levels of tissue mechanical forces (e.g., immobilization, beginning a new exercise or occupation). Longstanding physical therapy practices also suggest that externally applied mechanical forces can be used to reduce collagen deposition during tissue repair and scar formation (Cummings and Tillman, 1992). The mechanisms underlying these effects, however, are not well understood. In this study, we have used an ex vivo mouse subcutaneous tissue explant model and an in vivo mouse microinjury model to examine the effect of applying brief (10 min), static mechanical stretch on TGF-β...

BackgroundIn humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can be used to quantify dynamic changes in local connective tissue structure in vivo. We first performed combined ultrasound and histology examinations of the same tissue in two subjects undergoing surgery: in one subject, we examined the relationship of ultrasound to histological images in three dimensions; in the other, we examined the effect of a localized tissue perturbation using a previously developed robotic acupuncture needling technique. In ten additional non-surgical subjects, we quantified changes in tissue spatial organization over time during needle rotation vs. no rotation using ultrasound and semi-variogram analyses.Results3-D renditions of ultrasound images showed longitudinal echogenic sheets that matched with collagenous sheets seen in histological preparations. Rank correlations between serial 2-D ultrasound and corresponding histology images resulted in high positive correlations for semi-variogram ranges computed parallel (r = 0.79, p < 0.001) and perpendicular (r = 0.63, p < 0.001) to the surface of the skin, indicating concordance in spatial structure between the two data sets. Needle rotation caused tissue displacement in the area surrounding the needle that was mapped spatially with ultrasound elastography and corresponded to collagen bundles winding around the needle on histological sections. In semi-variograms computed for each ultrasound frame, there was a greater change in the area under the semi-variogram curve across successive frames during needle rotation compared with no rotation. The direction of this change was heterogeneous across subjects. The frame-to-frame variability was 10-fold (p < 0.001) greater with rotation than with no rotation indicating changes in tissue structure during rotation.ConclusionThe combination of ultrasound and semi-variogram analyses allows quantitative assessment of dynamic changes in the structure of human connective tissue in vivo.