Longitudinal FDG-PET scan study of brain changes in mice with cancer-induced bone pain and after morphine analgesia.

Morphine is the most commonly used drug for treating physical and psychological suffering caused by advanced cancer. Although morphine is known to elicit multiple supraspinal analgesic effects, its behavioral correlates with respect to the whole-brain metabolic activity during cancer-induced bone pain have not been elucidated. We injected 4T1 mouse breast cancer cells into the left femur bone marrow cavity of BALB/c mice. All mice developed limb use deficits, mechanical allodynia, and hypersensitivity to cold, which were effectively suppressed with morphine. Serial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was performed for each mouse before cancer induction (0 day), after cancer-induced bone pain was established (14 days), and during effective morphine treatment (16 days). The longitudinal FDG-PET imaging analysis demonstrated that cancer-induced bone pain increased glucose uptake in the insular cortex and hypothalamus and decreased the activity of the retrosplenial cortex. Morphine reversed the activation of the insular cortex and hypothalamus. Furthermore, morphine activated the amygdala and rostral ventromedial medulla and suppressed the activity of anterior cingulate cortex. Our findings of hypothalamic and insular cortical activation support the hypothesis that cancer-induced bone pain has strong inflammatory and affective components in freely moving animals. Morphine may provide descending inhibitory and facilitatory actions in the treatment of cancer-induced bone pain in a clinical setting.

Pulmonary rehabilitation improves heart rate variability at peak exercise, exercise capacity and health-related quality of life in chronic obstructive pulmonary disease.

OBJECTIVE: Patients with chronic obstructive pulmonary disease (COPD) appear to have impaired cardiac autonomic modulation with depressed heart rate variability (HRV). Pulmonary rehabilitation (PR) is recommended as an integral part of the management. However, the effect of PR on HRV at peak exercise remains unclear. METHODS: Sixty-four patients with COPD participated in a 12-week, 2 sessions-per-week, hospital-based PR program. Baseline and post-PR status were evaluated by spirometry, HRV, health-related quality of life (HRQL, St. George's Respiratory Questionnaire, SGRQ), cardiopulmonary exercise test, respiratory muscle strength, and dyspnea Borg's scale. RESULTS: After PR, there were significant improvements in the time and frequency domains of HRV with increased standard deviation of the normal R-R intervals, difference between adjacent normal R-R intervals within a given time minus one, high-frequency and decreased low-frequency, as well as concurrent improvements in HRQL, exercise capacity, dyspnea score, and respiratory muscle strength (all p < 0.05). CONCLUSIONS: PR results in significant improvements in autonomic function, with concurrent improvements in HRQL and exercise capacity.

Benefits of pulmonary rehabilitation in patients with COPD and normal exercise capacity.

BACKGROUND: Pulmonary rehabilitation (PR) is beneficial for patients with COPD, with improvement in exercise capacity and health-related quality of life. Despite these overall benefits, the responses to PR vary significantly among different individuals. It is not clear if PR is beneficial for patients with COPD and normal exercise capacity. We aimed to investigate the effects of PR in patients with normal exercise capacity on health-related quality of life and exercise capacity. METHODS: Twenty-six subjects with COPD and normal exercise capacity were studied. All subjects participated in 12-week, 2 sessions per week, hospital-based, out-patient PR. Baseline and post-PR status were evaluated by spirometry, the St George's Respiratory Questionnaire, cardiopulmonary exercise test, respiratory muscle strength, and dyspnea scores. RESULTS: The mean FEV1 in the subjects was 1.29 ± 0.47 L/min, 64.8 ± 23.0% of predicted. After PR there was significant improvement in maximal oxygen uptake and work rate. Improvements in St George's Respiratory Questionnaire scores of total, symptoms, activity, and impact were accompanied by improvements of exercise capacity, respiratory muscle strength, maximum oxygen pulse, and exertional dyspnea scores (all P < .05). There were no significant changes in pulmonary function test results (FEV1, FVC, and FEV1/FVC), minute ventilation, breathing frequency, or tidal volume at rest or exercise after PR. CONCLUSIONS: Exercise training can result in significant improvement in health-related quality of life, exercise capacity, respiratory muscle strength, and exertional dyspnea in subjects with COPD and normal exercise capacity. Exercise training is still indicated for patients with normal exercise capacity.