dynorphins and Neoplasms

This review has covered the five potential causes for opioid poorly responsive pain, namely (a) a loss of opioid receptors on the spinal terminals of C-fibres as a result of peripheral nerve damage, (b) an accumulation of morphine-3-glucuronide, (c) changes in the non-opioid peptides, F8Fa or CCK, either spinally or supraspinally, (d) actions of the opioid peptide dynorphin and (e) spinally generated hypersensitive states via activation of the NMDA receptor. The loss of opioid receptors is likely to be important where peripheral nerve pathology or compression occurs, but the evidence suggests that increasing the dose will overcome the reduced opioid response. Morphine-3-glucuronide is unlikely to be a factor, nor is dynorphin, but the endogenous peptides CCK and F8Fa may be important. Finally, there is an association between the NMDA receptor and hyperalgesia/allodynia and reduced opioid sensitivity. Dextrorphan and ketamine reduce NMDA mediated events and so are available to test this hypothesis.

Topics: Analgesics, Opioid; Animals; Central Nervous System; Clonidine; Dextromethorphan; Dextrorphan; Dynorphins; Humans; Morphine; N-Methylaspartate; Neoplasms; Neurophysiology; Neuroprotective Agents; Pain; Rats; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid; Sympatholytics

We looked for opioid peptides and their precursors in 108 tumors of both neuroendocrine and nonneuroendocrine origin, using a monoclonal "pan-opioid" antibody, 3-E7, which recognizes the tetrapeptide Tyr-Gly-Gly-Phe (the sequence responsible for pharmacologic activity in all known opioid peptides), in conjunction with polyclonal antibodies directed against representative peptides of each of the three precursors (alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B). Using the avidin-biotin immunoperoxidase technique, we observed consistent cytoplasmic immunoreactivity (at least focally) in all of 15 adrenal pheochromocytomas, all of 6 thyroid medullary carcinomas, and all of 5 pituitary adenomas. Opioid staining was also observed in parathyroid adenomas (8 of 9), pancreatic islet-cell tumors (7 of 10), carcinoid tumors from various sites (18 of 26), and paragangliomas (1 of 2). There was no immunoreactivity in pulmonary small-cell carcinomas, Merkel-cell tumors of skin, neuroblastomas, or any of the non-neuroendocrine tumors examined. The expression of alpha-endorphin, [met]enkephalin-Arg-Gly-Leu, and dynorphin B varied from tumor to tumor; however, positive staining with the "pan-opioid" antibody was found in each tumor containing at least one of the three precursors. Opioid peptide immunoreactivity was also detected in non-neoplastic cells of the adrenal medulla, pancreatic islets, pituitary, intestinal and bronchial mucosa, and intestinal myenteric plexuses. We conclude that opioid expression within tumors is most likely due to enhanced expression of a normal cell product and that opioid peptides are useful markers of neuroendocrine differentiation in many tumors.

Topics: alpha-Endorphin; Antibodies, Monoclonal; Biomarkers, Tumor; Dynorphins; Endocrine System Diseases; Endorphins; Humans; Immunoenzyme Techniques; Neoplasms; Neurosecretory Systems; Peptide Fragments

Seven cases of chronic pain were treated by intrathecal administration of 30 micrograms of beta-endorphin and dynorphin-(1-13). Compared with saline, both peptides were able to suppress pain for periods up to 4.5 and 7 hours on the average, respectively. No significant side reactions were noticed during the entire investigation.

Topics: Adult; Aged; beta-Endorphin; Cerebral Infarction; Dynorphins; Endorphins; Female; Herpes Zoster; Humans; Injections, Spinal; Male; Middle Aged; Neoplasms; Pain, Intractable; Peptide Fragments; Wounds, Gunshot