Participation of central GABAA receptors in the trigeminal processing of mechanical allodynia in rats

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta (IL-1β) (1 ng/10 µL) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A (GABAA) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the IL-1β-induced mechanical allodynia. In the control group, application of GABA (100 µM) or muscimol (3 µM) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the IL-1β-treated rats. These results suggest that some large myelinated Aβ fibers gain access to the nociceptive system and elicit pain sensation via GABA(A) receptors under inflammatory pain conditions.

Mutations of the Pre-S Region in HBV-Associated Liver Cirrhosis and Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: According to the recent research, mutations in the HBV pre-S region may have an impact on the progression of hepatitis B virus(HBV)-related liver disease. The aim of this study was to clarify the frequency and location of naturally occurring mutations in the pre-S region of HBV, and their possible effects on the clinical course of HBV-associated chronic liver diseases. METHODS: HBV DNA was extracted from the sera of 15 patients (8 with liver cirrhosis and 7 with hepatocellular carcinoma). The pre-S sequence was amplified via polymerase chain reaction, subcloning and sequenced. RESULTS: All patients had point mutations in the pre-S region. Nine of 10 mutation sites (90%) in the pre-S1 region, and 4 of 5 mutation sites (80%) in the pre-S2 region were identical in both liver cirrhosis and hepatocellular carcinoma. Deletions were detected in seven patients (4 with liver cirrhosis and 3 with hepatocellular carcinoma). Among the 4 patients with liver cirrhosis, three had deletion in 5'-end of the pre-S2 region and one spanning the 3'-end of the pre-S1 to 5'-end of the pre-S2 region. All 3 patients with hepatocellular carcinoma had deletions in 5'-end of the pre-S1 region, and two patients had simultaneous deletion spanning the 3'-end of the pre-S1 to the 5'-end of the pre-S2. CONCLUSION: The pre-S mutants were frequently detected in HBV-associated liver cirrhosis or hepatocellular carcinoma and the point mutations or deletions in the pre-S gene were clustered in specific regions.

Detection of ras gene mutations in human cancer by PCR-SSCP / 대한암학회지

No abstract available.