Paradoxical pain

Morley, J. S.; Miles, JohnB.; Wells, J. C. D.; Bowsher, David

doi:10.1016/0140-6736(92)93067-w

Cited by 56 publications

(16 citation statements)

References 4 publications

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“…Heroin is considered to be a prodrug, and it exerts its effects through its active metabolites, 6-acetylrnorphine, morphine, and morphine-6-glucuronide. Findings in animals indicated that morphine-3-glucuronide may antagonize the analgesic action of morphine and rnorphine-6-glucuronide (28), and morphine-3-glucuronide was suggested that morphine-3-glucuronide may be responsible for the paradoxical pain observed in patient-given morphine (29).…”

Section: Discussionmentioning

confidence: 99%

Plasma Concentrations of Heroin and Morphine-Related Metabolites after Intranasal and Intramuscular Administration

Skopp

Ganssmann

Cone

et al. 1997

Journal of Analytical Toxicology

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The disposition of heroin and its metabolites was investigated in four healthy male volunteers following intranasal administration of 6 and 12 mg heroin hydrochloride. In addition, two doses of 6 mg heroin hydrochloride were injected intramuscularly for comparison of pharmacokinetic parameters. Serum samples were analyzed for heroin, 6-acetylmorphine, and morphine by solid-phase extraction-gas chromatography-mass spectrometry. The concentration of morphine glucuronides was determined by high-performance liquid chromatography based on the native fluorescence of the conjugates. Major findings were rapidly rising and declining terminal phases for heroin and 6-acetylmorphine and slowly declining phases of morphine and metabolites after both routes of administration. The area under the curve values of morphine-3-glucuronide depended on dose but not on route of administration. The apparent terminal half-lives of morphine-3-glucuronide ranged from 2.2 to 5.2 h for intranasally administered heroin and were 3.0 and 1.7 h for the intramuscularly applied drug. A mean morphine-3-glucuronide-heroin area-under-curve ratio of 93 for the intranasal route as compared with 38 for the intramuscular route demonstrated that circulating amounts of heroin were about half the size after intranasal administration of the same dose.

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Section: Discussionmentioning

confidence: 99%

Plasma Concentrations of Heroin and Morphine-Related Metabolites after Intranasal and Intramuscular Administration

Skopp

Ganssmann

Cone

et al. 1997

Journal of Analytical Toxicology

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“…column from Waters was operated at room temperature. On the other hand, different reports have underlined the role of morphine metabolites in determining the adverse effects occurring with prolonged or high doses of morphine, probably responsible of the poor opioid responsiveness [18,20]. 12H2O 10 mM adjusted at pH 3.5 with H 3 PO4.The flow-rate was 1.2 ml/min and the column effluent was monitored at 214 nm.…”

Section: Morphine Morphine 3-glucuronide and Morphine 6-glucuronidementioning

confidence: 99%

Opioid plasma concentration during switching from morphine to methadone: preliminary data

Mercadante

Bianchi

Villari

et al. 2003

Support Care Cancer

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Opioid switching is often used to improve the opioid response in cancer patients experiencing poor analgesia or adverse effects. However, no data are available on plasmatic changes of opioids and their metabolites during these phases, and whether there exists a relationship with the clinical events. In a prospective study of 10 consecutive cancer patients on oral morphine but with uncontrolled pain (greater >4 on a numerical scale of 0 to 10) and/or moderate to severe opioid adverse effects (on a level of 2 and 3 of a verbal scale) and not responsive to adjuvant medications, switching to oral methadone was performed using a fixed ratio of 5:1, leaving extra-doses of 1/5 of the daily dose of methadone calculated as needed. Blood samples were obtained at the same hour for four days, before the switching, and then on day 1, 2, and 3. The intensity of pain and the adverse effects were assessed daily to calculate the switching score before and after switching. Completed blood samples were obtained in 9 patients. One patient was separately considered, because of his renal impairment. Significant improvements in pain intensity as well as adverse effects within an average period of 1-2 days were observed. Morphine, morphine-6-glucuronide, and morphine-3-glucuronide were progressively cleared from plasma to almost disappear within three days. Methadone rapidly achieved a stable concentration in 1-2 days. The doses of methadone were changed, but not significantly, and tended to decrease in the following days, according to the clinical situation. The results of this study confirm the need to stop rapidly morphine, and to use a priming dose of methadone, rather than using progressive decrements and increments of morphine and methadone, respectively, during opioid switching. This method allows for a rapid clearance of morphine and its metabolites are rapidly cleared, except in patients with renal failure. Opioid plasma changes substantially overlap the clinical changes observed in these patients, in terms of benefit between analgesia and adverse effects.

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“…This hyperalgesia may conceivably result from the relative discontinuation of receptor activation that follows the opioid's peak action, though it so far has been attributed to morphine metabolites (Woolf, 1981) and to unspecific actions of morphine on non-opioid receptors (Yaksh & Harty, 1988). The chronic administration of opioids in some patients suffering chronic pain has been reported to aggravate the pain (Brodner & Taub, 1978;Potter et al, 1989;Morley et al, 1992;Sjrgen et al, 1993Sjrgen et al, , 1998Heger et al, 1999;see also: Schofferman, 1993;Sjrgen & Eriksen, 1994;Savage, 1993) and to produce a so-called universal hyperalgesia of excruciating intensity (Sjrgen et al, 1993) and with a diffuse anatomic pattern (Savage, 1993). Interestingly, this hyperalgesia may disappear rather than be enhanced after the opioid treatment is discontinued (Taylor et al, 1980;Savage, 1996), suggesting that it may be caused by the sign reversal reported here.…”

Section: A Bruins Slot Et Almentioning

confidence: 86%