Disrupted Sleep and Delayed Recovery from Chronic Peripheral Neuropathy Are Distinct Phenotypes in a Rat Model of Metabolic Syndrome

Background: Sleep apnea, hypertension, atherosclerosis, and obesity are features of metabolic syndrome associated with decreased restorative sleep and increased pain. These traits are relevant for anesthesiology because they confer increased risks of a negative anesthetic outcome. This study tested the one-tailed hypothesis that rats bred for low intrinsic aerobic capacity have enhanced nociception and disordered sleep. Methods: Rats were developed from a breeding strategy that selected for low aerobic capacity runners (LCR) and high aerobic capacity runners (HCR). Four phenotypes were quantified. Rats underwent von Frey sensory testing (n = 12), thermal nociceptive testing (n = 12), electrographic recordings of sleep and wakefulness (n = 16), and thermal nociceptive testing (n = 14) before and for 6 weeks after a unilateral chronic neuropathy of the sciatic nerve. Results: Paw withdrawal latency to a thermal nociceptive stimulus was significantly (P < 0.01) lower in LCR than HCR rats. There were also significant differences in sleep, with LCR rats spending significantly (P < 0.01) more time awake (18%) and less time in nonrapid eye movement sleep (-19%) than HCR rats. Nonrapid eye movement sleep episodes were of shorter duration (-34%) in LCR than HCR rats. Rapid eye movement sleep of LCR rats was significantly more fragmented than rapid eye movement sleep of HCR rats. LCR rats required 2 weeks longer than HCR rats to recover from peripheral neuropathy. Conclusions: Rodents with low aerobic capacity exhibit features homologous to human metabolic syndrome. This rodent model offers a novel tool for characterizing the mechanisms through which low aerobic function and obesity might confer increased risks for anesthesia.