PubMed · 15852589
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Scott Smith. 2005. Safe sedation.. https://pubmed.ncbi.nlm.nih.gov/15852589/
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Previous studies have demonstrated that morphine, administered systemically or directly into the periaqueductal gray (PAG), produces a significantly greater degree of antinociception in males in comparison with females. Because the midbrain PAG and its descending projections to the rostral ventromedial medulla (RVM) constitute an essential neural circuit for opioid-based analgesia, the present studies were conducted to determine whether sex differences in the anatomical organization of the PAG-RVM pathway, and its activation during persistent inflammatory pain, could account for sex-based differences in opioid analgesia. In the rat, retrograde tracing was combined with Fos immunocytochemistry to investigate sexual dimorphism in the organization of the PAG-RVM circuit and its activation by persistent inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA). The ability of morphine to suppress the activation of the PAG-RVM circuit was also examined. Sexually dimorphic retrograde labeling was observed within the dorsomedial and lateral/ventrolateral PAG at all rostrocaudal levels, with females having significantly more PAG-RVM output neurons in comparison with males. While no sex differences were noted in the activation of the PAG by persistent inflammatory pain, significantly more PAG-RVM cells were activated in males in comparison with females. Systemic administration of morphine significantly suppressed CFA-induced Fos in the PAG in males only. The results of these studies demonstrate that both the anatomical organization and the functional activation of the PAG-RVM circuit are sexually dimorphic and may provide the anatomical substrate for sex-based differences in morphine analgesia.
We made a single intraperitoneal (IP) injection of morphine sulfate (40 mg/kg) into winter flounder and seawater acclimated rainbow trout at 10 degrees C and then followed its disposition by measuring the change in plasma morphine concentration for 100 h using a morphine specific ELISA. Disposition also was followed for 6h after a single IV injection of 7.5mg morphine sulfate in winter flounder. Plasma morphine reached a maximum within an hour post-injection IP and then decreased in a bi-exponential fashion with a rapid distribution phase followed by a slower elimination phase. The disposition was slower in flounder than in trout even though the fish were held at the same temperature. For example, plasma clearance was 76 mL h(-)(1) kg(-)(1) in the flounder but was almost twice as much in the trout (153 mL h(-)(1) kg(-)(1)) and mean residence time was 27.9h in the flounder but was 7.0 h in the trout. The present study is the first comprehensive pharmacokinetic analysis for any analgesic in an ectotherm, and our results show that: 1) significant intra-specific variation exists between fishes: and 2) the disposition of morphine in fish is approximately one order of magnitude slower than it is in mammals. These differences may be due in part to mass specific differences in cardiac output.
To evaluate the efficacy and tolerability of oxycodone in cancer-related pain, we conducted a systematic review of randomized controlled trials. Four studies, comparing oral oxycodone with either oral morphine (n = 3) or oral hydromorphone (n = 1), were suitable for meta-analysis. Standardized mean differences in pain scores comparing oxycodone with control groups were pooled using random-effects models. Overall, there was no evidence that mean pain scores differed between oxycodone and control drugs (pooled standardized mean difference, 0.04; 95% confidence interval [CI], -0.29 to 0.36; P = .8; I(2) = 62%). In meta-regression analyses, pain scores were higher for oxycodone compared with morphine (0.20; 95% CI, -0.04 to 0.44) and lower compared with hydromorphone (-0.36; 95% CI, -0.71 to 0.00), although these effect sizes were small. The efficacy and tolerability of oxycodone are similar to morphine, supporting its use as an opioid for cancer-related pain.