RESUMO
BACKGROUND: Exercise is often prescribed as a therapy for chronic pain. Short-term exercise briefly increases the production of endogenous analgesics, leading to transient antinociception. In limited studies, exercise produced sustained increases in endogenous opioids, sustained analgesia, or diminished measures of chronic pain. This study tests the hypothesis that regular aerobic exercise leads to sustained reversal of neuropathic pain by activating endogenous opioid-mediated pain modulatory systems. METHODS: After baseline measurements, the L5 and L6 spinal nerves of male Sprague-Dawley rats were tightly ligated. Animals were randomized to sedentary or 5-week treadmill exercise-trained groups. Thermal and tactile sensitivities were assessed 23 h after exercise, using paw withdrawal thresholds to von Frey filaments and withdrawal latencies to noxious heat. Opioid receptor antagonists were administered by subcutaneous, intrathecal, or intracerebroventricular injection. Opioid peptides were quantified using immunohistochemistry with densitometry. RESULTS: Exercise training ameliorated thermal and tactile hypersensitivity in spinal nerve-ligated animals within 3 weeks. Sensory hypersensitivity returned 5 days after discontinuation of exercise training. The effects of exercise were reversed by using systemically or intracerebroventricularly administered opioid receptor antagonists and prevented by continuous infusion of naltrexone. Exercise increased ß-endorphin and met-enkephalin content in the rostral ventromedial medulla and the mid-brain periaqueductal gray area. CONCLUSIONS: Regular moderate aerobic exercise reversed signs of neuropathic pain and increased endogenous opioid content in brainstem regions important in pain modulation. Exercise effects were reversed by opioid receptor antagonists. These results suggest that exercise-induced reversal of neuropathic pain results from an up-regulation of endogenous opioids.
Assuntos
Neuralgia/fisiopatologia , Limiar da Dor/fisiologia , Condicionamento Físico Animal/fisiologia , Receptores Opioides/fisiologia , Animais , Tronco Encefálico/metabolismo , Modelos Animais de Doenças , Encefalina Metionina/metabolismo , Masculino , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Neuralgia/reabilitação , Limiar da Dor/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores Opioides/efeitos dos fármacos , beta-Endorfina/metabolismoRESUMO
The authors describe the expansion of The University of Arizona College of Medicine from Tucson, Arizona, into Phoenix. They explain how the new Phoenix program, in partnership with Arizona State University, is one college of medicine for the state of Arizona, governed by a single accreditation by the Liaison Committee for Medical Education (LCME). The authors present 21 lessons to be considered early in a medical school expansion process: clearly establish responsibility, authority, and accountability; define activities under university purview and those that require broader engagement; delineate college-wide versus campus-specific functions; clearly define the intent of the new initiative; get frequent input from the LCME; use LCME input to ensure a student focus; be cautious in using consultants; use respected local "brokers"; create a single locus for input and concerns; educate constituencies about medical school requirements; engage leadership to create linkages across sites; encourage communication between leaders in both sites; discriminate between shared and distinctive local curriculum elements; consider the effort and experience required to develop a full curriculum versus those required to develop specific local curricular areas; create simple, transparent admission processes; define faculty profiles for the new program; ensure sufficient resources for core faculty; budget based on national metrics; create core mission-based principles to frame discussions and decisions; segregate clinical affiliation discussions from curriculum and recruitment of basic science faculty; and ensure sufficient land. Although these observations are most relevant to institutions planning expansions of already accredited programs, they derive from principles and practical considerations with wider applicability.