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Background. Although evidence suggests that therapeutic ultrasound (TU) in combination with treadmill training (TT) suppresses nerve injury-associated pain, the molecular mechanisms for this action are not clear. Objective. The purpose of this research was to study the possible beneficial effects of TU and TT, alone and in combination, on 2 clinical indicators of neuropathic pain and correlate these findings with changes in inflammatory mediators within the spinal cord. Our experimental model used the well-known chronic constriction injury (CCI) of the rat sciatic nerve. Design. This was an experimental study. Methods. Each group contained 10 rats. Group 1 underwent only the CCI procedure. Group 2 underwent a sham operation where the sciatic nerve was exposed but not ligated. Group 3 had the sham operation followed by both IT and TU. Groups 4, 5, and 6 underwent the CCI procedure followed by TT alone, TU alone, and both the TT and TU interventions, respectively. Heat and mechanical sensitivity, interleukin-6 (IL-6), interleukin-10 GL-10), and ionized calcium binding adaptor molecule 1 (Iba1) were evaluated. Results. Compared with group 1 animals, TT or TU, or both, produced smaller decreases in mechanical withdrawal threshold and heat withdrawal latencies. The combination of TT and TU was more effective than either treatment alone. In addition, rats that received these treatments did not express the upregulation of IL-6 and Iba1 in their spinal cords on postoperative days 14 and 28, as was found in the group 1 animals. Limitations. These experimental findings may not be generalizable to humans. Conclusions. The combination of TU and TT reduces neuropathic pain more than either modality alone. This beneficial effect appears related to downregulation of proinflammatory IL-6 and Ibal, while upregulating the anti-inflammatory IL-10., Peripheral nerve injury commonly leads to neuropathic pain characterized by thermal hyperalgesia, mechanical allodynia, spontaneous pain, and mechano-hyperalgesia. (1) Peripheral and central sensitization of nociceptive pathways are crucial to the [...]

Background. Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain. Objective. The purpose of this study was to investigate whether TENS altered postincisional allodynia, substance P, and proinflammatory cytokines in a rat model of skin-muscle incision and retraction (SMIR). Design. This was an experimental study. Methods. High-frequency (100-Hz) TENS therapy began on postoperative day 3 and was administered for 20 minutes daily to SMIR-operated rats by self-adhesive electrodes delivered to skin innervated via the ipsilateral dorsal rami of lumbar spinal nerves L1-L6 for the next 27 days. The expressions of substance P, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL- 1β) in the spinal cord and mechanical sensitivity to von Frey stimuli (4g and lOg) were evaluated. Results. The SMIR-operated rats displayed a marked hypersensitivity to von Frey stimuli on postoperative day 3. In contrast to the SMIR-operated rats, SMIR- operated rats after TENS administration showed a quick recovery of mechanical hypersensitivity. On postoperative days 3, 16, and 30, SMIR-operated rats exhibited an upregulation of substance P and cytokines (TNF-α, IL-6, and IL-1β) in the spinal cord, whereas SMIR-operated rats after TENS therapy inhibited that upregulation. By contrast, the placebo TENS following SMIR surgery did not alter mechanical hypersensitivity and the levels of spinal substance P, TNF-α, IL-6, and IL-1β. Limitations. The experimental data are limited to animal models and cannot be generalized to postoperative pain in humans. Conclusions. The results revealed that TENS attenuates prolonged postoperative allodynia following SMIR surgery. Increased levels of spinal substance P and proinflammatory cytokines, activated after SMIR surgery, are important in the processing of persistent postsurgical allodynia. The protective effect of TENS may be related to the suppression of spinal substance P and proinflammatory cytokines in SMIR- operated rats., Prolonged postincisional pain is a major factor in reducing quality of life (1) and increasing the utilization of health services. (2, 3) Although postsurgical pain can be managed by administration [...]