Overuse injury is a frequent diagnosis in occupational medicine and athletics. Using an established model of upper extremity overuse, we sought to characterize changes occurring in the forepaws and forelimbs of mature female rats (14–18 months of age). Thirty-three rats underwent a 4-week shaping period, before performing a high-repetition low-force (HRLF) task for 12 weeks, with the results being compared to 32 mature controls. HRLF animals showed a reduced grip strength versus controls. ELISAs carried out in the HRLF rats, versus controls, showed elevated levels of IL1-α in tendons, IL1-α and TNF-α in distal bones/entheses, and TNF-α, MIP1-α/CCL3, and CINC-2/CXCL-3 in serum, as well as IL-6 in forelimb muscles and tendons, and IL-10 in serum. HRLF rats had elevated collagen deposition in the forepaw intrinsic muscles (i.e., fibrosis), entheseal microdamage, and articular cartilage degradation versus the control rats. CD68/ED1+ osteoclasts and single-nucleated cells were elevated in distal forelimb metaphyses of the HRLF animals, versus controls. Declines in grip strength correlated with muscle fibrosis, entheseal microdamage, articular cartilage damage, distal bone/enthesis IL1-α, and serum IL-6. These data demonstrate inflammatory and persistent degradative changes in the forearm/forepaw tissues of mature female animals exposed to prolonged repetitive tasks, changes with clinical relevance to work-related overuse injuries in mature human females.

Background/Objectives: We have demonstrated in human cadavers and canines that nerve transfer to bladder vesical nerve branches is technically feasible for bladder reinnervation after nerve injury. We further clarify here that sacral (S) ventral rami contribute to these vesical branches in 36 pelvic sides (in 22 human cadavers). Methods: Gross post-mortem visualization and open anterior abdominal approaches were used, as was micro-CT of sacral nerve bundles, for further confirmation when needed. Results: Considerable between and within-subject variation was observed. Sacral (S) ventral rami contributions to vesical nerves were observed as shared contributions from several rami or, in a few cases, from single rami: S2 alone (6%), S3 alone (6%), S2 and S3 (28%), S3 and S4 (28%), S2–S4, 14%, L5 in combination with S1–S4 (6%), S1 and S2 (6%), and S3–S5 (3%). The most common contributor to these shared or single rami contributions was from the S3 ventral ramus, which contributed 100% of the time on the left side and 79% on the right side. Side-to-side asymmetry was observed in 10 of 14 cadavers examined bilaterally (71%). Conclusions: This characterization of the anatomical variation in sacral ventral rami contributions to the bladder will ultimately aid in developing therapeutics for patients with bladder dysfunction.

Neurotrophic factors and reactive oxygen species (ROS) modulate neuronal plasticity. In a model of a lower motor neuron lesioned bladder, somatic nerve transfer was used as a reinnervation strategy. Levels of neurotrophins, ROS, and TNF-α in bladder mucosa and muscle layers collected from three groups of adult female dogs: (1) Decentralized, via bilateral transection of coccygeal and sacral spinal roots, lumbar 7 dorsal roots, and hypogastric nerves, then 6–21 mo recovery; (2) reinnervated (ObNT-Reinn), after similar decentralization for 12 mo, then bilateral obturator-to-vesical nerve transfer and 8–12 mo recovery; and (3) Controls. In mucosa, BDNF and ROS levels were highest in ObNT-Reinn bladders, GDNF and TNF-α levels were restored to Control levels in ObNT-Reinn bladders (lowest in Decentralized). NT-3 and ARTN were lower in ObNT-Reinn and Decentralized bladders versus Controls. In muscle, ROS was lower in ObNT-Reinn muscle versus Controls. BDNF mucosa levels correlated with bladder axonal density and detrusor layer thickness; and GDNF mucosal correlated with bladder contraction after vesical or transferred obturator nerve electrical stimulation, as did BDNF and GDNF muscle levels. The increased BDNF and GDNF in bladders that underwent somatic nerve transfer with subsequent recovery suggest that BDNF and GDNF may help promote the reestablishment of bladder innervation.