buprenorphine and Lung-Neoplasms

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline (1 ml/kg). Tumours were imaged and welfare was assessed using body weight, behaviour and nociceptive responses. In study 1, BALB/c mice were inoculated with 4T1 mammary carcinoma or saline during surgery or anaesthesia. As pre-treatment with a single buprenorphine dose appeared beneficial to cancer growth consistency, a second cohort of mice additionally received saline or buprenorphine at 12 and 24 h. Surgery resulted in increased mammary tumour growth and lung metastases. These unwanted effects were lessened by buprenorphine pre-treatment, especially when given repeatedly. Mammary tumour-bearing mice became less active and nociceptive thresholds declined over time, indicating some discomfort as tumours grew. In study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to determine whether meloxicam or buprenorphine affected cancer seeding of the lungs. While meloxicam reduced B16 lung seeding, buprenorphine did not. Mechanical thresholds decreased as cancer developed in mice bearing melanoma, but the magnitude of this was insufficient to conclude that there were any significant welfare concerns. This study highlights the scientific value in utilising non-surgical models, where possible. When surgery must be performed at the time of tumour inoculation, the effects of this should be controlled with appropriate analgesics to enhance the value and possibly translation of the research.

Topics: Analgesics; Animal Welfare; Animals; Breast Neoplasms; Buprenorphine; Cell Line, Tumor; Disease Models, Animal; Female; Lung Neoplasms; Mammary Neoplasms, Experimental; Melanoma, Experimental; Meloxicam; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Pain; Thiazines; Thiazoles; Xenograft Model Antitumor Assays

Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12 h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model.

Topics: Analgesics, Opioid; Animal Welfare; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Neoplasms; Buprenorphine; Disease Models, Animal; Drug Therapy, Combination; Female; Injections; Longevity; Lung Neoplasms; Meloxicam; Mice; Mice, SCID; Osteosarcoma; Pain Management; Thiazines; Thiazoles; Tibia

Topics: Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Drug Therapy, Combination; Humans; Lung Neoplasms; Methadone; Middle Aged; Morphine; Musculoskeletal Pain; Neuralgia; Palliative Care

Not all opioids employed in clinical practice share the same immunosuppressive properties. The potent partial micro-agonist buprenorphine appears to exhibit a neutral effect on the immune responses. Surgery stress is associated with decreased natural killer cell activity (NK) and enhancement of tumor metastasis in rats. We analyzed the ability of buprenorphine to prevent the effects of experimental surgery on HPA activation (plasma corticosterone levels), NK activity and lung diffusion of the NK sensitive tumor MADB106. Buprenorphine (0.1mg/kg) was compared with equianalgesic doses of fentanyl (0.1mg/kg) and morphine (10mg/kg) in this animal model. In normal animals morphine and fentanyl stimulate the HPA axis, decrease NK activity and augment tumor metastasis, while buprenorphine is devoid of these effects. Surgery significantly raised corticosterone levels, suppressed NK activity and increased MADB106 metastasis. Only buprenorphine was able to prevent the neuroendocrine and immune system alterations and ameliorate the increase of tumor metastasis induced by surgical stress. These preclinical findings suggest that an adequate treatment of surgically induced stress immunosuppression with an opioid drug devoid of immunosuppressive effects may also play a protective role against the metastatic diffusion following cancer surgery.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Breast Neoplasms; Buprenorphine; Corticosterone; Disease Models, Animal; Fentanyl; Hypothalamo-Hypophyseal System; Immune Tolerance; Killer Cells, Natural; Laparotomy; Lung Neoplasms; Male; Morphine; Neoplasm Metastasis; Neoplasms, Experimental; Pituitary-Adrenal System; Rats; Rats, Inbred F344; Stress, Physiological

We characterized anticancer effects of opioid analgesics that are clinically used for cancer patients for pain relief. Treatment with 100 microM buprenorphine, a representative analgesic, induced cell death of human carcinomas, such as A549 (squamous epithelial cell of lung cancer), MCF-7 (breast cancer) and N417 (small cell of lung cancer), but not in KATO III (gastric cancer) cells as evaluated by alamar blue assay. Among 18 clinically utilized and related analgesics, buprenorphine and loperamide showed potent inhibition of cell viability. However, these anti-cancer effects were not affected by opioid receptor antagonists nor by pertussis toxin. Buprenorphine-induced cell death occurred as early as 1 h after the addition, and its T1/2 of cell viability inhibition was 3 h. The cell death manifested the characteristics of apoptosis, such as DNA-laddering and nuclear fragmentation, which were sensitive to a caspase inhibitor, Z-Asp-CH2-DCB. The nuclear fragmentation was independent of cell cycle phase specificity. The activity of caspase-3-like protease which is known to be closely related to apoptotic DNA laddering was markedly enhanced by buprenorphine. However, the inhibition of cell viability by buprenorphine was not affected by the caspase inhibitor. These findings suggest that some opioid analgesics induce typical apoptotic features sensitive to the caspase inhibitor, while also inhibition of cell viability insensitive to the inhibitor.

Topics: Analgesics, Opioid; Apoptosis; Breast Neoplasms; Buprenorphine; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Caspase 1; Caspase 3; Caspases; Cell Cycle; Cell Survival; DNA Fragmentation; Female; Flow Cytometry; Humans; Loperamide; Lung Neoplasms; Molecular Structure; Stomach Neoplasms; Tumor Cells, Cultured

The influence of different lung resection methods on pulmonary function was studied in 34 patients suffering from bronchial carcinoma. Daily measurements from the 1st to 10th postoperative day reveal the greatest losses of function after right upper lobectomy. Lower lobectomies or left upper lobectomy resulted in a less extensive loss of function. Recovery of function mainly occurs in the first 4 days after operation. Centrally acting analgetics are followed by a loss in pulmonary function whereas locally applied analgetics improve early postoperative function.

Topics: Adult; Aged; Airway Resistance; Analgesics; Buprenorphine; Carcinoma, Bronchogenic; Female; Humans; Lung Neoplasms; Lung Volume Measurements; Male; Meperidine; Middle Aged; Nerve Block; Pain, Postoperative; Pneumonectomy; Postoperative Complications; Respiratory Insufficiency

Topics: Administration, Sublingual; Aged; Buprenorphine; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Pain, Intractable

Epidural injections of buprenorphine were given for postoperative pain relief to a patient with pulmonary carcinoma who underwent a right upper lobectomy. Paraplegia occurred postoperatively and the patient's neurological status deteriorated after each injection of epidural narcotic. Laminectomies on the third postoperative day revealed an expanded oxidized cellulose (Oxycel) pledget in the epidural space. Neurologic dysfunction after epidural narcotic administration was caused by the oxidized cellulose which had migrated into the epidural space following use for surgical haemostasis and subsequently expanded with the narcotic solution and blood.

Topics: Aged; Buprenorphine; Humans; Injections, Epidural; Lung Neoplasms; Male; Pain, Postoperative; Paraplegia; Postoperative Complications