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Objective. This study aims to evaluate the effectiveness of neural mobilization (NM) in the management of sensory dysfunction and nerve degeneration related to experimental painful diabetic neuropathy (PDN). Methods. This is a pre-clinical animal study performed in the streptozocin-induced diabetic rat model. Three groups were included: a treatment group of rats with PDN receiving NM under anesthesia (PDN-NM, n = 10), a sham treatment group of rats with PDN that received only anesthesia (PDN-Sham, n = 9), and a vehicle control group with nondiabetic animals (Vehicle, n = 10). Rats in the PDN-NM and PDN-Sham groups received 1 treatment session on days 10, 12, and 14 after streptozocin injection, with a 48-hour rest period between sessions. Behavioral tests were performed using von Frey and Plantar tests. Evaluation for peripheral nerve degeneration was performed through measuring protein gene product 9.5-positive intra-epidermal nerve fiber density in hind-paw skin biopsies. All measurements were performed by a blinded investigator. Results. The behavioral tests showed that a single NM session could reduce hyperalgesia, which was maintained for 48 hours. The second treatment session further improved this treatment effect, and the third session maintained it. These results suggest that it requires multiple treatment sessions to produce and maintain hypoalgesic effects. Skin biopsy analysis showed that the protein gene product 9.5-positive intra-epidermal nerve fiber density was higher on the experimental side of the PDN-NM group compared with the PDN-Sham group, suggesting NM may mitigate the degeneration of peripheral nerves. Conclusion. This study demonstrated that NM may be an effective method to manage experimentally induced PDN, potentially through mitigation of nerve degeneration. Further studies are needed to develop standardized protocols for clinical use. Impact. These findings provide neurophysiological evidence for the use of NM in PDN and can form the basis for the development of physical therapy-based programs in clinics. Keywords: Diabetic Neuropathies, Nerve Degeneration, Pain Management, Introduction Diabetic neuropathy (DN) is one of the most common diabetes-related complications. Approximately 25%-50% of patients with diabetes seek medical attention for the management of DN. (1,2) The clinical manifestation [...]

Background. Painful diabetic neuropathy (PDN) is a common complication in patients with diabetes. It is related to ischemic nerve damage and the increase in the levels of proinflammatory mediators, such as tumor necrosis factor [alpha] (TNF-[alpha]) and interleukin 1[beta] (IL-1[beta]). Neural mobilization may have the potential to alleviate PDN, but it has not yet been tested. Also, the physiological mechanism of neural mobilization is unclear. Objective. The objective of this study was to investigate treatment effect and physiological mechanism of neural mobilization. Design. This was an experimental study using rats with streptozocin (or streptozoto-cin)-induced type 1 diabetes. Methods. Three groups were used in the study, the control group (vehicle), the diabetes group (PDN group), and the neural mobilization treatment group (PDN-NM group) (n = 6). Rats in the vehicle group were healthy rats. Rats in the PDN and PDN-NM groups were rats with diabetes. Rats in the PDN-NM group received treatment in the right sciatic nerve, whereas rats in the PDN group did not. Mechanical pain sensitivity and the levels of IL-1[beta] and TNF-[alpha] in the sciatic nerve branches and trunk, the L4 to L6 dorsal horn ganglion, and the spinal cord dorsal horn were measured. Results. Mechanical allodynia was alleviated after treatment, but the effect was limited to the treatment side. The concentrations of proinflammatory cytokines were decreased in the nerves that received treatment compared with those on the other side, indicating that neural mobilization may reduce mechanical sensitivity by decreasing the concentrations of local sensitizing agents. Limitations. A limitation of this study was that no direct measurement of nerve blood flow was done. Conclusions. The results of this study showed that neural mobilization effectively alleviated mechanical allodynia in rats with PDN. The side that received treatment had lower concentrations of TNF-[alpha] and IL-1[beta] in the sciatic nerve branches and sciatic nerve trunk; this result may have been related to the alleviation of mechanical allodynia., Painful diabetic neuropathy (PDN) is one of the most common causes of chronic pain in patients with diabetes; approximately 30% of patients with diabetes have pain related to PDN. (1,2) [...]