Accepted

Diabetic peripheral neuropathy (DPN) is a common condition that is associated with neuromuscular dysfunction and peripheral sensory impairment. These deficits predispose patients to sensory and motor system limitations, foot ulcers and a high risk of falls. Exercise training has been proposed as an effective tool to alleviate neural deficits and improve whole-body function. Here we review the effects of DPN on neuromuscular function, the mechanisms underlying this impairment, and the neural and muscular adaptations to exercise training. Muscle dysfunction is an early hallmark of DPN. Deficits in muscle strength, power, mass and a greater fatigability are particularly severe in the lower extremity muscles. Non-enzymatic glycation of motor proteins, impaired excitation-contraction coupling and loss of motor units have been indicated as the main factors underlying muscular dysfunction. Among the exercise-based solutions, aerobic training improves neural structure and function and ameliorates neuropathic signs and symptoms. Resistance training induces marked improvement of muscle performance and may alleviate neuropathic pain. A combination of aerobic and resistance training (i.e., combined training) restores small sensory nerve damage, reduces symptoms, and improves muscle function. The evidence so far suggests that exercise training is highly beneficial and should be included in the standard care for DPN patients.

Cerium oxide nanoparticles (CeONP), having potent antioxidant properties, are highly promising nanomaterials for treatment of diseases in which oxidative stress from excessive reactive oxygen species (ROS) plays a critical role in the pathogenesis and progression. However, most previously reported CeONP formulations were not efficiently cleared from the body, precluding their clinical translation. Herein, we report ultrasmall CeONP that can mitigate activation of macrophages and subsequent acute inflammation. It is found that these CeONP can effectively scavenge reactive species, inhibit macrophage activation, and minimize their recruitment and infiltration to the inflammation site, which lead to alleviation of edema and pain hypersensitivity. Moreover, we demonstrate that CeONP can be effectively excreted from the body within 24 h of systemic administration, minimizing long-term toxicity concerns. Altogether, our findings suggest that CeONP may be explored as both antioxidant and anti-inflammatory agents that can reduce acute inflammation with a better safety profile than existing nanoparticles.

Pain is the most common reason for physician consultations and the number one reason for missed work or school days is musculoskeletal pain. Pain management is utilized for easing the suffering and improving the quality of life of those living with chronic pain. Over the past several decades, physicians have become increasingly willing to prescribe opioids to manage pain. However, the opioid use can cause side effects as poor coordination, sedation, mood swings, depression, and anxiety combined with a dependence on the drugs. In the rehabilitation setting, patients benefit most when their health providers utilize a multimodal approach combining different types of therapies and when patients take on a significant role in optimal management of their own pain. The use of light as a therapeutic alternative form of medicine to manage pain and inflammation has been proposed to fill this void. Photobiomodulation therapy applied in the form of low-intensity light amplification by the stimulated emission of radiation (LASER) and lightemitting diode (LED) has been shown to reduce inflammation and swelling, promote healing, and reduce pain for an array of musculoskeletal conditions. There is evidence that photobiomodulation therapy reduces pain intensity in non-specific knee pain, osteoarthritis, pain post-total hip arthroplasty, fibromyalgia, temporomandibular diseases, neck pain, and low back pain. Therefore, the purpose of this review was to presented the up-to-dated evidence about the effects of lowintensity LASER and LED (photobiomodulation therapy) on pain control of the most common musculoskeletal conditions. We observed that the photobiomodulation therapy offers a noninvasive, safe, drug-free, and side-effect-free method for pain relief of both acute and chronic musculoskeletal conditions as well as fibromyalgia.