Effects of epidural capsaicin on nociceptive threshold and neurological functions in rabbits.

UNLABELLED: Capsaicin, as a principle active component of Chili peppers, is popularly consumed by many people around the world. Whether capsaicin-induced neuropathy alters the function of sensory neurons is still unknown. OBJECTIVE: The objectives of this study were to determine the effects of epidural capsaicin on nociceptive threshold and neurological functions in a rabbit model. DESIGN: An intrathecal injection system was set up using a rabbit model. Rabbits were treated with capsaicin at doses of 0.04, 0.10, and 0.20 mg/kg once. The changes in neurological functions and morphology of the spinal cord and spinal nerve roots were determined within 24 hours. Changes in the nociceptive threshold in the hind limbs of the rabbits were observed for 30 days. METHODS: Capsaicin's effect on the changing neurological functions was evaluated by the neurological functional scores. The structural changes of spinal cord and spinal nerve roots were observed by hematoxylin and eosin staining and transmission electron microscopy. The nociceptive threshold changes in the rabbits were measured by the responding time for pain induced by a thermostimulation. RESULTS: The results showed that capsaicin reversed changes in the neurological function of rabbit hindlimbs. In the 0.10 and 0.20 mg/kg groups, structural abnormalities were found in the rabbit's spinal nerves. Capsaicin also significantly increased the pain threshold in rabbits when compared with the control group (P < 0.05 or P < 0.01). The maximum values of pain threshold were found in the 0.10 mg/kg capsaicin group after 3 days of capsaicin treatment. CONCLUSION: With the exception of a potential toxicity, capsaicin may be a potential candidate agent for providing pain relief of both neuropathic and nociceptive conditions.

The prion protein binds thiamine.

Although highly conserved throughout evolution, the exact biological function of the prion protein is still unclear. In an effort to identify the potential biological functions of the prion protein we conducted a small-molecule screening assay using the Syrian hamster prion protein [shPrP(90-232)]. The screen was performed using a library of 149 water-soluble metabolites that are known to pass through the blood-brain barrier. Using a combination of 1D NMR, fluorescence quenching and surface plasmon resonance we identified thiamine (vitamin B1) as a specific prion ligand with a binding constant of ~60 µM. Subsequent studies showed that this interaction is evolutionarily conserved, with similar binding constants being seen for mouse, hamster and human prions. Various protein construct lengths, both with and without the unstructured N-terminal region in the presence and absence of copper, were examined. This indicates that the N-terminus has no influence on the protein's ability to interact with thiamine. In addition to thiamine, the more biologically abundant forms of vitamin B1 (thiamine monophosphate and thiamine diphosphate) were also found to bind the prion protein with similar affinity. Heteronuclear NMR experiments were used to determine thiamine's interaction site, which is located between helix 1 and the preceding loop. These data, in conjunction with computer-aided docking and molecular dynamics, were used to model the thiamine-binding pharmacophore and a comparison with other thiamine binding proteins was performed to reveal the common features of interaction.

Solid phase synthesis of acylglycine human metabolites.

Acylglycines represents a large and important class of human metabolites. They are often used in medicine to identify fatty acid oxidation disorders. A highly efficient solid phase synthesis approach to obtain these clinically important compounds is developed via coupling reaction between glycine-preloaded Wang resin and a set of carboxylic acids. The developed methodology facilitates the preparation of several structurally-diverse acylglycines with high yields and purity.