Complicated Pain Management in a CYP450 2D6 Poor Metabolizer.

Pain Pract. 2007 Nov 6; [Epub ahead of print]

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Complicated Pain Management in a CYP450 2D6 Poor Metabolizer.

Foster A, Mobley E, Wang Z.

Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, Georgia, USA.

We describe the case of a patient with significant adverse effects from posttraumatic analgesic therapy with opioid analgesics who was found by microarray analysis to have a CYP2D6 genotype predictive of a poor metabolizer phenotype. In addition to her poor tolerance and limited response to opioid analgesics, she developed further discomfort when the antiemetic promethazine was administered to treat her gastrointestinal adverse effects. In our discussion we review the literature about the clinical impact of CYP450 2D6 polymorphisms in treatment with the commonly used opioid analgesics codeine, oxycodone, hydrocodone, hydromorphone, and morphine, as well as the antiemetic promethazine. The case we present, as well as the literature we review, demonstrates the clinical utility of CYP2D6 genotyping in patients with adverse effects from analgesia therapy.

PMID: 17986163 [PubMed - as supplied by publisher]

Rat brain opioid peptides-circadian rhythm is under control of melatonin.

Neuropeptides. 2007 Nov 5; [Epub ahead of print]

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Rat brain opioid peptides-circadian rhythm is under control of melatonin.

Miguel Asai MA, Lilian Mayagoitia LM, David García DG, Gilberto Matamoros-Trejo GM, Marcela Valdés-Tovar MV, Phillipe Leff PL.

Laboratorio de Análisis Químicos, Instituto Nacional de Psiquiatría, Calzada México-Xochimilco #101, Col. San Lorenzo Huipulco, C.P. 14370, México D.F., Mexico.

Several experiments have revealed an Endogenous Opioid System (EOS)-circadian rhythm. The brain-borne hormone, melatonin (MEL) has been shown to regulate the organism photoperiodic activity and may be implicated in the EOS-circadian rhythm. To explore this hypothesis, we studied the effect of functional pinealectomy on the EOS-circadian rhythm by measuring the immunoreactive content of Met-Enkephalin, Leu-Enkephalin and Synenkephalin in both hypothalamus and hippocampus of the rat brain, using standard radioimmunoassay procedures. Experimental animals exposed to white fluorescent light (WFL) for 15days (<50lux), displayed a disruption of the EOS-circadian rhythm, showing that absence of MEL induced a significant decrease of tissue content of enkephalin peptides at 01:00h during the dark-phase of the 24-h circadian rhythm, when compared to control rats. Functional pinealectomized rats exposed to 4 or 6h period of darkness (used to revert the effects induced by the absence of melatonin) significantly increased the tissue content of ME-IR and LE-IR, when compared to both controls and non-exposed WFL-treated rats. In addition, subcutaneous administration of exogenous melatonin (10, 100, 150, 300, 600mug/kg), in WFL-treated animals produced significant dose-dependent increases of ME-IR in both brain regions tested. Finally, luzindole (melatonin receptor antagonist) administration, was not able to prevent the enkephalin tissue increase, induced with the MEL administration (150mug/kg). This data suggest that MEL not only regulates the EOS-circadian rhythm, but also appears to modulate their synthesis in the rat brain from their respective neurons.

PMID: 17988732 [PubMed - as supplied by publisher]