PubMed · 13986767
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E SATOYOSHI. 1962. [Sciatica].. https://pubmed.ncbi.nlm.nih.gov/13986767/
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Intramuscular injections are still part of routine care in the treatment of children. Vaccines, premedications and analgesics are administered by this route. The pain associated with an intramuscular injection is severe, the risk of complications is increased, and pharmacodynamics and pharmacokinetics are unpredictable. In many cases, equivalent alternatives of rectal, oral or intranasal routes of administering pharmacologic agents exist. Intramuscular injection of analgesics and premedications to children are-except in case of emergencies-obsolete. This demand corresponds to the guidelines of the World Health Organization (WHO) and the International Association for the Study of Pain (IASP).
We are reporting on the case of an 11-year old girl with a malignant tumour. The extreme pain throughout the body could not be treated by conventional methods. By intravenous application of a morphine and s-ketamine mixture we were able to achieve a very effective analgesic result. Apart from the opiate effect of the morphine the decisive factor was the NMDA-antagonism of the s-ketamine. The latter suppresses central sensitisation and chronic pain and reduces or even prevents the development of opioid tolerance. It was possible to use smaller opiate doses more effectively, thus reducing the side effects of the pain therapy. Under associated whole-body thermochemotherapy the girl experienced general pain relief and we were able to return to conventional therapy with a fentanyl plaster.
Elevated nitric oxide (NO) production has been implicated in the development of morphine antinociceptive tolerance. This study was conducted to establish the temporal relationship between morphine-induced increases in neuronal NO and loss of pharmacologic activity. Five groups of rats equipped with microdialysis probes in the jugular vein and hippocampus received an intravenous infusion of saline or morphine (0.3, 1, 2, or 3 mg/kg/h) for 8 h. Morphine concentrations in the blood and hippocampal microdialysate were determined by LC/MS-MS; NO production was quantified with an amperometric sensor implanted in the contralateral hippocampus. Antinociceptive effect was monitored at selected time points during and following infusion by electrical stimulation vocalization. The data were fit with a pharmacokinetic/pharmacodynamic model to obtain parameters governing morphine disposition, stimulation of NO production, antinociception, and antinociceptive tolerance development. An additional three groups of rats were pretreated with l-arginine, the NO precursor (100, 300, or 500 mg/kg/h for 8 h), to elevate NO concentrations prior to morphine infusion. Morphine administration resulted in a dose-dependent increase in NO production; the time course of altered NO production coincided with the development of antinociceptive tolerance. l-arginine pretreatment initially enhanced morphine-induced analgesia early in the morphine infusion. However, this NO-associated increase in opioid response dissipated rapidly due to a dominant NO-induced loss of antinociception. Pharmacodynamic modeling suggested that this latter effect was consistent with a hyperalgesic response. These data define a strong, time-dependent relationship between morphine-induced stimulation of NO production and tolerance development, identify specific NO-induced alterations in nociceptive processing after morphine administration, and indicate that NO is a key mediator of antinociceptive tolerance development.