Emerging Relationships between Exercise, Sensory Nerves, and Neuropathic Pain

Previous trials have evaluated the effects of aerobic training alone and of resistance training alone on glycemic control in type 2 diabetes, as assessed by hemoglobin A1c values. However, none could assess incremental effects of combined aerobic and resistance training compared with either type of exercise alone. To determine the effects of aerobic training alone, resistance training alone, and combined exercise training on hemoglobin A1c values in patients with type 2 diabetes. Randomized, controlled trial. 8 community-based facilities. 251 adults age 39 to 70 years with type 2 diabetes. A negative result on a stress test or clearance by a cardiologist, and adherence to exercise during a 4-week run-in period, were required before randomization. Aerobic training, resistance training, or both types of exercise (combined exercise training). A sedentary control group was included. Exercise training was performed 3 times weekly for 22 weeks (weeks 5 to 26 of the study). The primary outcome was the change in hemoglobin A1c value at 6 months. Secondary outcomes were changes in body composition, plasma lipid values, and blood pressure. The absolute change in the hemoglobin A1c value in the combined exercise training group compared with the control group was -0.51 percentage point (95% CI, -0.87 to -0.14) in the aerobic training group and -0.38 percentage point (CI, -0.72 to -0.22) in the resistance training group. Combined exercise training resulted in an additional change in the hemoglobin A1c value of -0.46 percentage point (CI, -0.83 to -0.09) compared with aerobic training alone and -0.59 percentage point (CI, -0.95 to -0.23) compared with resistance training alone. Changes in blood pressure and lipid values did not statistically significantly differ among groups. Adverse events were more common in the exercise groups. The generalizability of the results to patients who are less adherent to exercise programs is uncertain. The participants were not blinded, and the total duration of exercise was greater in the combined exercise training group than in the aerobic and resistance training groups. Either aerobic or resistance training alone improves glycemic control in type 2 diabetes, but the improvements are greatest with combined aerobic and resistance training. ClinicalTrials.gov registration number: NCT00195884.

Immune cells and glia interact with neurons to alter pain sensitivity and to mediate the transition from acute to chronic pain. In response to injury, resident immune cells are activated and blood-borne immune cells are recruited to the site of injury. Immune cells not only contribute to immune protection but also initiate the sensitization of peripheral nociceptors. Through the synthesis and release of inflammatory mediators and interactions with neurotransmitters and their receptors, the immune cells, glia and neurons form an integrated network that coordinates immune responses and modulates the excitability of pain pathways. The immune system also reduces sensitization by producing immune-derived analgesic and anti-inflammatory or proresolution agents. A greater understanding of the role of the immune system in pain processing and modulation reveals potential targets for analgesic drug development and new therapeutic opportunities for managing chronic pain.

During "nondamaging" exercise, skeletal muscle markedly releases interleukin (IL)-6, and it has been suggested that one biological role of this phenomenon is to inhibit the production of tumor necrosis factor (TNF)- alpha, which is known to cause pathogenesis such as insulin resistance and atherosclerosis. To test this hypothesis, we performed three experiments in which eight healthy males either rested (CON), rode a bicycle for 3 h (EX), or were infused with recombinant human IL-6 (rhIL-6) for 3 h while they rested. After 2.5 h, the volunteers received a bolus of Escherichia coli lipopolysaccharide endotoxin (0.06 ng/kg) i.v. to induce low-grade inflammation. In CON, plasma TNF-alpha increased significantly in response to endotoxin. In contrast, during EX, which resulted in elevated IL-6, and rhIL-6, the endotoxin-induced increase in TNF-alpha was totally attenuated. In conclusion, physical exercise and rhIL-6 infusion at physiological concentrations inhibit endotoxin-induced TNF-alpha production in humans. Hence, these data provide the first experimental evidence that physical activity mediates antiinflammatory activity and suggest that the mechanism include IL-6, which is produced by and released from exercising muscles.