PubMed · 7488501
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G C Fenn, S Ratcliffe. 1995. Tramadol.. https://doi.org/10.1093/bja%2F75.4.501
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Dihydroetorphine is a novel opioid that is an extremely potent analgesic in rodents. The reinforcing potency was determined in rats trained to self-administer heroin and compared to those of fentanyl, heroin, 6-acetylmorphine and morphine for assessment of the abuse potential of dihydroetorphine using a procedure that determines the dose-effect curve in individual sessions. Dihydroetorphine produced a bimodal dose-effect curve similar to that of other opioids. Potency ratios were determined with morphine for the ascending and descending limbs of the dose-effect curve, as well as the dose that yielded maximal response rate. Fentanyl, heroin and 6-acetylmorphine were approximately 100, 8 and 2 times more potent than morphine in maintaining self-administration, respectively. Dihydroetorphine was roughly 1500 to 3000 times more potent than morphine, however, depending upon the limb of the dose-effect curve used for comparison. These potency ratios of dihydroetorphine to morphine were somewhat less than has been reported for analgesia assays, and therefore this compound may have some clinical advantages over other opioids. However, these studies indicate significant abuse liability for dihydroetorphine given its potency in maintaining self-administration in these animals.
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Bone pain is one of the most frequent causes of pain in patients with cancer, and the levels of metastases and bone pain are not directly correlated. Nociceptors in the periosteum are probably stimulated by halisteresis or by inflammatory oedema leading to an increase in the intraosseous pressure. Some authors believe that the nociceptors in bone are mediated via intraosseous mechanoreceptors in the bone-matrix. At a low pain level the initial treatment is acetylsalicylic acid, paracetamol or other nonsteroidal antiinflammatory drugs. At increasing pain level initial doses of oral opioids are added. In severe bone pain, where conventional therapy seems difficult, opioids are administered by invasive techniques. In localised bone pain palliative radiation is the first treatment of choice. Corticosteroids induce an analgetic effect indirectly by reducing the inflammatory oedema, inhibiting the synthesis of prostaglandins and may inhibit excitatory nerve fibres. Endocrine treatment, calcitonin and biophosphonates have shown a documented pain-relieving effect in patients with disseminated breast and prostate cancer. Chemotherapy has shown a pain-relieving effect in patients with disseminated breast cancer, surgical intervention is used in stabilizing osteolytic bones before or after a fracture ensuring a reasonable relief of pain.