In this study, histopathological and biochemical changes due to chronic usage of morphine or tramadol in liver and kidney were assessed in rats. Thirty male Wistar rats (180-220 g) were included and divided into three groups. Normal saline (1 ml) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4, 8, 10 mg/kg/day in the first, second and the third ten days of the study, respectively. Tramadol group (n = 10), received the drug intraperitoneally at doses of 20, 40 and 80 mg/kg/day in the first, second and the third ten days of the study, respectively. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatinin, blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were measured in the serum. Liver and kidney specimens were evaluated by light microscopy. Serum ALT, AST, LDH, BUN and creatinin levels were significantly higher in morphine group compared to the control group. Serum LDH, BUN and creatinin levels were significantly increased in the morphine group compared to the tramadol group. The mean MDA level was significantly higher in morphine group compared to the tramadol and control groups (P < 0.05). Light microscopy revealed severe centrolobular congestion and focal necrosis in the liver of morphine and tramadol groups, but perivenular necrosis was present only in the morphine group. The main histopathologic finding was vacuolization in tubular cells in morphine and tramadol groups. Our findings pointed out the risk of increased lipid peroxidation, hepatic and renal damage due to long term use of opioids, especially morphine. Although opioids are reported to be effective in pain management, their toxic effects should be kept in mind during chronic usage.

Histopathologic changes in rat brain due to chronic use of morphine and/or tramadol in progressively increased doses were investigated in this study. Thirty male Wistar rats (180-220 g) were included and divided into three groups. Normal saline (1 ml/kg) was given intraperitoneally as placebo in the control group (n = 10). Morphine group (n = 10) received morphine intraperitoneally at a dose of 4 mg/kg/day for the first 10 days, 8 mg/kg/day between 11-20 days, and 12 mg/kg/day between 21-30 days. The tramadol group (n = 10) received the drug intraperitoneally at doses of 20, 40, and 80 mg/kg/day in the first, second, and the third 10 days of the study, respectively. All rats were decapitated on the 30th day and the brain was removed intact for histology. The presence and the number of red neurons, which are a histologic marker of apoptosis, were investigated in the parietal, frontal, temporal, occipital, entorhinal, pyriform, and hippocampal CA1, CA2, CA3 regions. Red neurons were found in morphine and tramadol groups but not in the control group. The total number of red neurons was not different in morphine and tramadol groups, but the numbers of red neurons were significantly higher in the temporal and occipital regions in tramadol group as compared with the morphine group (p < .05). In conclusion, chronic use of morphine and/or tramadol in increasing doses is found to cause red neuron degeneration in the rat brain, which probably contributes to cerebral dysfunction. These findings should be taken into consideration when chrome use of opioids is indicated.

Recently, most studies reported magnesium as a N-methyl-D-aspartate receptor antagonist and its analgesic and perioperative anaesthetic effects have been discussed with central desensitization pathway. We investigated the effects of caudal ropivacaine plus magnesium and compared with ropivacaine alone on postoperative analgesia requirements. After hospital ethic committee's consent, 60 patients (ASA I-II, 2-10 years old) who had lower abdominal or penoscrotal surgery were enrolled in the study. After general anaesthesia induction, caudal blockage was applied. Patients were randomly assigned in two groups. Ropivacaine 0.25% was administered to Group R (n=37), ropivacaine 0.25% plus 50 mg magnesium to Group RM (n=23) in 0.5 ml kg-1 volume. Postoperative analgesia level was recorded at 15 min and 1, 2, 3, 4, 6 h by using Paediatric Objective Pain Scale (POPS) and The Children's Hospital of Eastern Ontoria Pain Scale (CHEOPS). Postoperative motor blocks were evaluated with Modified Bromage Motor Block Scale. According to demographic characteristics, there were no significant differences between the two groups (P>0.05). POPS, CHEOPS, Bromage Motor Scales, analgesia duration and adverse effects were similar in Group R and Group RM. It has been shown that addition of magnesium as an adjuvant agent to local anaesthetics for caudal analgesia has no effect on postoperative pain and analgesic need.

Recent experimental studies have described protective effect of ischemic preconditioning (IPC) on ischemia-reperfusion (I/R) injury of the intestine. We hypothesize that to reach a new point of view on the effect of IPC in intestinal barrier function, the relationship between I/R-induced mucosal injury and apoptosis must first be clarified. The present study was undertaken to investigate the role of IPC on intestinal apoptosis and probable contributions of bcl-2 expression to this process. We also investigated the effect of intestinal IPC on ileal malondyaldihyde levels. Forty-four male Wistar rats were randomized into four groups each consisting of 11 rats: sham-operated control, I/R group (30 min of superior mesenteric artery occlusion), IPC-I/R group (10 min of temporary artery occlusion prior before an ischemic insult of 30 min), and IPC alone group (10 min of preconditioning). Twenty-four hours later, ileum samples were obtained. Ileal malondyaldihyde levels were increased in the I/R group (31.9 +/- 18.8 vs. 106.8 +/- 39.8) but not in the IPC alone and IPC-I/R groups (38.1 +/- 13.6 and 44.7 +/- 12.7; P < 0.01). The number of apoptotic cells was significantly lower in IPC-I/R group than that of I/R group, and these findings were further supported by DNA laddering and M30 findings. Diminished bcl-2 expression observed in the ileal specimens of I/R group was prevented by IPC. Our results indicate that IPC may provide a protective effect on ileal epithelium and that this effect is probably the result of a significant increase in the expression of bcl-2 after the insult. The reversal of apoptosis by IPC might help preserving the vitality of intestinal structures that have a critical function, cessation of which often leads to multiorgan dysfunction syndrome.

Objectives: To examine in a prospective, randomized, double-blind, placebo-controlled study the analgesic effect of periprostatic nerve block and/or intravenous synthetic opioid administration during a 12-core prostate biopsy. Patients and Methods: Patients were prospectively randomized to receive unilateral periprostatic lidocaine administration and/or intravenous synthetic opioid (meperidine or tramadol) administration. Placebo groups received sterile normal saline. Unilateral infiltration was performed and biopsy was begun on this side. The degree of pain was recorded using the visual analog scale/numeric analog scale (VAS/NAS) score before the procedure, during probe introduction into the rectum, during unilateral periprostatic nerve blockade, during the first 6-core biopsy and during the second 6-core biopsy, and 30 min after biopsy completion. Results: Most of the patients had mild or moderate pain (VAS/NAS <6) during the actual biopsy procedure. However, no significant differences existed between the groups with regard to the pain scores at any time (p > 0.05). Compared with pain scores, no significant differences existed between the first 6-core (blocked side) and second 6-core biopsies (p > 0.05). Conclusion: Periprostatic lidocaine infiltration and/or intravenous synthetic opioid analgesics are not beneficial in significantly reducing pain during biopsy. We think that most of the patients do have pain during biopsy, however the intensity of pain is tolerable and does not require analgesics.