PubMed · 9533668
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N T Mathew. 1998. Medication misuse headache.. https://doi.org/10.1177/0333102498018s2109
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There is some doubt as to the effectiveness of opioids in the management of neuropathic pain. We therefore examined the actions of morphine and the opioid-like peptide nociceptin (both 1 mu) on dorsal root ganglion (DRG) neurons that were isolated from control or from nerve-injured rats. Both substances reduced omega-conotoxin (CTX) GVIA-sensitive, N-type Ca2+ channel current and small persistent nifedipine/ CTX-insensitive (non-N, non-L type) current. Nifedipine-sensitive L-type current was unaffected. The effect of nociceptin was antagonized by naloxone benzoylhydrazone (nalbzoh) but not by naloxone. Sciatic nerve section (axotomy) profoundly reduced the effects of morphine and the mu-receptor agonist D-ala2, N-Me-Phe4,Gly-ol5 enkephalin (DAMGO). The effect of the kappa-agonist [(+)-(5alpha,7alpha, 8beta)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro(4, 5)dec-8-yl)-benzeneacetamide] (U69593) was unchanged, whereas the effect of nociceptin was increased. All agonists produced their strongest effects on the small, putative nociceptive cells and their weakest effects on the largest cells. The delta-receptor agonist, enkephalin D-pen2,5 (DPDPE), was without effect on control or on axotomized cells. These and other data suggest that the functional downregulation of mu-opioid receptors on sensory nerves contributes to the poor efficacy of opioids in neuropathic pain. Also, the increased effectiveness of nociceptin after axotomy supports the hypothesis that its actions are mediated via a "non-opioid" receptor. Pronounced suppression of Ca2+ channel current in axotomized DRG neurons by nociceptin led to a reduction in Ca2+-dependent K+ conductance and a marked increase in excitability. Despite this, the spinal administration of nociceptin or agonists that activate ORL1 (opioid-like orphan receptor) may prove to be of clinical interest in the management of neuropathic pain.
We recently reported that morphine inhibits growth of various human cancer cell lines (IC50/2.7-8.8 mM). We then extended the study using newly synthesized morphine derivatives, such as KT-90 and KT-87, which are analgesics 5 times more potent than morphine. KT-90 was found to inhibit growth of human cancer cell lines (IC50/42-70 microM) up to 80 times more potently than morphine. As for mechanisms of action, KT-90 and morphine induced apoptosis, and inhibited tumor necrosis factor alpha (TNF-alpha) gene expression induced by tumor promoters, okadaic acid and 12-O-tetradecanoylphorbol-13-acetate, associated with reduction of NF-kappaB DNA binding activity. This paper provides evidence that KT compounds confirmed the presence of anticancer activity of morphine in addition to its analgesic action.
Analgesic nephropathy is a slowly progressive disease caused by the chronic abuse of analgesic mixtures containing two analgesic components combined with potentially addictive substances (coffeine and/or codeine). Pathologically, the nephropathy is characterized by renal papillary necrosis with calcification and chronic interstitial nephritis sometimes in association with transitional-cell carcinoma of the uroepithelium. In the early stage, the clinical characteristics are polyuria, sterile pyuria, sometimes renal colic and haematuria. With further progression of the disease, there are the nonspecific symptoms of advanced renal failure. The incidence of classic analgesic nephropathy among Hungarian patients on chronic renal replacement therapy has proven. There is an urgent need for the estimation of analgesic nephropathy among patients with chronic renal disease and among patients with chronic pain presumably regularly taking analgesics in Hungary. As long as analgesic mixtures containing phenacetin or paracetamol and/or nonsteroidal antiinflammatory drugs and addictive substances are available "over-the-counter", analgesic nephropathy will continue to be a problem also in our country.