pregabalin and Ischemia

Ischemia-reperfusion injury is thought to be the most important factor affecting the success of liver surgery. Pregabalin has been studied to prevent ischemic reperfusion injury in many organs. The aim of this study was to investigate the role of pregabalin in preventing liver ischemic injury.. 40 male Wistar-Albino rats, 6-8 weeks old, were divided into 5 groups. Four groups other than the sham group were subjected to hepatic ischemia for 1 hour, followed by 2 hours of reperfusion. Effects of 30 mg/and 60 mg/kg pregabalin were evaluated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor α (TNF-α), nuclear factor-kappa B (NF-кB), interleukin (IL)-6 levels, measured in blood samples collected before and after ischemia. Apoptosis was measured by caspase-3, and tissue samples were evaluated for ischemia by histopathologic examination.. The 60 mg pregabalin group was significantly superior (p=0.024) to the N-acetylcysteine group and the 30 mg pregabalin group for AST levels (p=0.612 and p=0.807, respectively). The difference between before and after ischemia-reperfusion blood TNF-α levels was higher in the 60 mg pregabalin group, but not significantly different from the 30 mg pregabalin and N-acetylcysteine groups (p>0.05). Tissue TNF-α levels showed that 60 mg and 30 mg pregabalin treatment was more effective than no-treatment (p=0.011, p=0.033, respectively), but not superior to N-acetylcysteine (p>0.05).. It has been found that ischemia-reperfusion causes damage to the liver, and this damage may be irreversible if no treatment is given. Our study group, pregabalin molecule was found to be significantly effective in preventing ischemia-reperfusion injury and may have a therapeutic advantage over N-acetylcysteine.

Topics: Acetylcysteine; Alanine Transaminase; Analgesics; Animals; Aspartate Aminotransferases; Ischemia; Liver; Male; Pregabalin; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha

Progressive retinal ganglion cell (RGC) loss induced by retinal ischemia/reperfusion (RIR) injury leads to irreversible visual impairment. Pregabalin (PGB) is a promising drug for neurodegenerative diseases. However, with regard to RGC survival, its specific role and exact mechanism after RIR injury remain unclear. In this study, we sought to investigate whether PGB could protect RGCs from mitochondria-related apoptosis induced by RIR and explore the possible mechanisms.. C57BL/6J mice and primary RGCs were pretreated with PGB prior to ischemia/reperfusion modeling. The retinal structure and cell morphology were assessed by immunochemical assays and optical coherence tomography. CCK8 was used to assay cell viability, and an electroretinogram was performed to detect RGC function. Mitochondrial damage was assessed by a reactive oxygen species (ROS) assay kit and transmission electron microscopy. Western blot and immunofluorescence assays quantified the expression of proteins associated with the Akt/GSK3β/β-catenin pathway.. Treatment with PGB increased the viability of RGCs in vitro. Consistently, PGB preserved the normal thickness of the retina, upregulated Bcl-2, reduced the ratio of cleaved caspase-3/caspase-3 and the expression of Bax in vivo. Meanwhile, PGB improved mitochondrial structure and prevented excessive ROS production. Moreover, PGB restored the amplitudes of oscillatory potentials and photopic negative responses following RIR. The mechanisms underlying its neuroprotective effects were attributed to upregulation of the Akt/GSK3β/β-catenin pathway. However, PGB-mediated neuroprotection was suppressed when using MK2206 (an Akt inhibitor), whereas it was preserved when treated with TWS119 (a GSK3β inhibitor).. PGB exerts a protective effect against RGC apoptosis induced by RIR injury, mediated by the Akt/GSK3β/β-catenin pathway.

Topics: Animals; Apoptosis; beta Catenin; Caspase 3; Cell Survival; Glycogen Synthase Kinase 3 beta; Ischemia; Mice; Mice, Inbred C57BL; Pregabalin; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Reperfusion Injury; Retina; Retinal Ganglion Cells; Signal Transduction

Chronic post-ischemia pain was induced in anesthetized rats by placing a tourniquet at the ankle joint for 3 h, and removing it to allow reperfusion. The effectiveness of standard analgesic drugs to attenuate mechanical allodynia was assessed 2 and 7 days after ischemia/reperfusion. Only high doses of morphine, dexamethasone and pregabalin partially reduced mechanical allodynia 2 days post-ischemia/reperfusion, while other treatments (ibuprofen, acetaminophen, amitriptyline) were not effective. Furthermore, only the highest dose of pregabalin reduced mechanical allodynia 7 days post-ischemia/reperfusion. These results are consistent with findings that complex region pain syndrome-I pain is refractory to most standard analgesic treatments.

Topics: Amitriptyline; Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; gamma-Aminobutyric Acid; Hindlimb; Ischemia; Male; Morphine; Pain; Pain Measurement; Peripheral Nervous System Diseases; Physical Stimulation; Pregabalin; Rats; Rats, Long-Evans; Reflex Sympathetic Dystrophy; Regional Blood Flow; Reperfusion Injury

Spinal cord stimulation (SCS) is an effective tool in alleviating neuropathic pain. However, a number of well-selected patients fail to obtain satisfactory pain relief. Previous studies have demonstrated that i.t. baclofen and/or adenosine can enhance the SCS effect, but this combined therapy has been shown to be useful in less than half of the cases and more effective substances are therefore needed. The aim of this experimental study in rats was to examine whether gabapentin or pregabalin attenuates tactile allodynia following partial sciatic nerve injury and whether subeffective doses of these drugs can potentiate the effects of SCS in rats which do not respond to SCS. Mononeuropathy was produced by a photochemically induced ischaemic lesion of the sciatic nerve. Tactile withdrawal thresholds were assessed with von Frey filaments. Effects of increasing doses of gabapentin and pregabalin (i.t. and i.v.) on the withdrawal thresholds were analysed. These drugs were found to reduce tactile allodynia in a dose-dependent manner. In SCS non-responding rats, i.e. where stimulation per se failed to suppress allodynia, a combination of SCS and subeffective doses of the drugs markedly attenuated allodynia. In subsequent acute experiments, extracellular recordings from wide dynamic range neurones in the dorsal horn showed prominent hyperexcitability. The combination of SCS and gabapentin, at the same subeffective dose, clearly enhanced suppression of this hyperexcitability. In conclusion, electrical therapy and pharmacological therapy in neuropathic pain can, when they are inefficient individually, become effective when combined.

Topics: Acetates; Amines; Analgesics; Animals; Anticonvulsants; Calcium Channel Blockers; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Electric Stimulation; Electrophysiology; Gabapentin; gamma-Aminobutyric Acid; Injections; Ischemia; Male; Mononeuropathies; Pain; Pain Management; Posterior Horn Cells; Pregabalin; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Spinal Cord; Touch