buprenorphine and Neoplasm-Metastasis

Topics: Analgesics; Buprenorphine; Female; Genital Neoplasms, Female; Humans; Morphine; Neoplasm Metastasis; Pain Management

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

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

This case-report of a 78-year old patient, suffering from extreme pain caused by metastatic formation and pathological bone fractures, shows, that the epidural injection of buprenorphine is a good alternative compared to other means of pain-treatment. During almost four days heart rate, blood pressure and breathing frequency, as well as the general reactions of the patient, were observed. Few side effects and little discomfort make the method advisable for patients in poor general condition.

Topics: Aged; Anesthesia, Epidural; Breast Neoplasms; Buprenorphine; Chronic Disease; Epidural Space; Female; Femoral Neck Fractures; Humans; Injections; Morphinans; Neoplasm Metastasis; Pain