Co-administration of nalbuphine attenuates the morphine-induced anxiety and dopaminergic alterations in morphine-withdrawn rats.

INTRODUCTION: The classical effects of exogenous opioids, such as morphine, are predominantly mediated through µ-opioid receptors. The chronic use of morphine induces anxiety-like behavior causing functional changes in the mesolimbic dopaminergic system. The mixed µ/κ-agonist, nalbuphine, used either as an analgesic or as an adjuvant with morphine, produces different and opposite effects. However, whether nalbuphine can be used to antagonize morphine-induced anxiety and dopaminergic alterations is not fully known. OBJECTIVE: This study aimed to compare acute and chronic effects of nalbuphine on morphine-induced anxiety and dopaminergic alterations in rats. METHODS: Male adult Wistar albino rats were made opioid-dependent by administering increasing doses of morphine (5-25 mg/kg; i.p.; b.i.d.). Withdrawal was induced by naloxone (1 mg/kg, i.p.), 4 h after the last morphine injection. Anxiety-like behavior was measured using Activity Monitor (Coulbourn Instruments, Inc. USA). Thereafter, the animals were sacrificed and the brain dissected out and the level of cAMP and the transcriptional and translational expression of TH was measured. Nalbuphine was co-administered with morphine, acutely and chronically, at various doses (0.1, 0.3, 1.0, 3.0 mg/kg, i.p.). RESULTS: Morphine-dependent rats showed a significant higher anxiety and cAMP levels and a significant decrease in the expression of TH. Co-administration of chronic doses of nalbuphine attenuates the higher anxiety, cAMP levels, and upregulates the TH expressions; however, the acute nalbuphine treatment does not attenuate the morphine-induced side effects. CONCLUSION: Therefore, nalbuphine might have an important role in attenuating the anxiety and the effects of the dopaminergic pathway and may have potential in the treatment of opioid addiction.

Spur on posterior arch of atlas with fatal spinal cord compression - a case report

The atlas vertebra has many developmental variations in its structure, mainly on its posterior arch with prevalence varying from 0.69% to 4%. It includes a spur on the anterior arch, a thickened anterior arch, posterior pointiculus and incomplete posterior arch among others. Some of the variations are associated with spinal stenosis, such as hypoplastic arch and ossification of the posterior longitudinal ligament. The anomalies are generally asymptomatic, but occasionally cause neck pain, and rarely myelopathy. In the case reported here, a spur was present in the midline on the anterior surface of the posterior arch of the atlas. This led to gradual compression of the cervical spinal cord with progressive quadriplegia, numbness and death. Myelopathy was confirmed by histopathology

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The human trochlear and abducens nerves at different ages - a morphometric study.

The trochlear and abducens nerves (TN and AN) control the movement of the superior oblique and lateral rectus muscles of the eyeball, respectively. Despite their immense clinical and radiological importance no morphometric data was available from a wide spectrum of age groups for comparison with either pathological or other conditions involving these nerves. In the present study, morphometry of the TN and AN was performed on twenty post-mortem samples ranging from 12-90 years of age. The nerve samples were processed for resin embedding and toluidine blue stained thin (1µm) sections were used for estimating the total number of myelinated axons by fractionator and the cross sectional area of the nerve and the axons by point counting methods. We observed that the TN was covered by a well-defined epineurium and had ill-defined fascicles, whereas the AN had multiple fascicles with scanty epineurium. Both nerves contained myelinated and unmyelinated fibers of various sizes intermingled with each other. Out of the four age groups (12-20y, 21-40y, 41-60y and >61y) the younger groups revealed isolated bundles of small thinly myelinated axons. The total number of myelinated fibers in the TN and AN at various ages ranged from 1100-3000 and 1600-7000, respectively. There was no significant change in the cross-sectional area of the nerves or the axonal area of the myelinated nerves across the age groups. However, myelin thickness increased significantly in the AN with aging (one way ANOVA). The present study provides baseline morphometric data on the human TN and AN at various ages.

Duration of injury correlates with necrosis in caerulein-induced experimental acute pancreatitis: implications for pathophysiology.

Pancreatic acinar cell necrosis is indicative of severe pancreatitis and the degree of necrosis is an index of its outcome. We studied whether the dose and duration of injury correlates with severity, particularly in terms of necrosis, in caerulein-induced acute pancreatitis (AP) in Swiss albino mice. In addition to control group 1 (G1), groups 2 and 3 received four injections of caerulein every hour but were sacrificed at five hours (G2) and nine hours (G3) respectively, and group 4 received eight injections and was sacrificed at nine hours (G4). The severity of pancreatitis was assessed histopathologically and biochemically. The histopathological scores of pancreatitis in groups 3 and 4 were significantly higher than in groups 1 and 2 (4 vs. 1, 4 vs. 2, 3 vs. 1, 3 vs. 2; P < 0.05). TUNEL-positive apoptotic cells were significantly higher in groups 2 and 3 compared with groups 1 and 4 (P < 0.05). Necrosis was significantly more in group 4 than other groups (37.49% (4.68) vs. 19.97% (1.60) in G2; 20.36% (1.56) in G3; P = 0.006 for G 2 vs. 4 and P = 0.019 for G 3 vs. 4). Electron microscopy revealed numerous autophagosomes in groups 2 and 3 and mitochondrial damage and necrosis in group 4. The pancreatic and pulmonary myeloperoxidase activity in group 4 was significantly higher than that in the other groups (P < 0.01). Hence, severity of pancreatitis is a function of the dose of injurious agent, while inflammation is both dose and duration dependent, which may also explain the wide spectrum of severity of AP seen in clinical practice.