Intrathecal gabapentin does not act as a hyperpolarization-activated cyclic nucleotide-gated channel activator in the rat formalin test.

BACKGROUND AND OBJECTIVE: Gabapentin, an anticonvulsant with analgesic effect, has been reported to be an activator of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. In this study, we tested the effect of intrathecal ZD7288, an HCN channel inhibitor, and its interaction with intrathecal gabapentin in the rat formalin test. METHODS: Male Sprague-Dawley rats (250-300 g) with an intrathecal catheter were intraplantarly injected with formalin (5% formaldehyde, 50 microl) in the right hindpaw. Ten minutes before formalin injection, gabapentin (100 or 200 microg) was given intrathecally. ZD7288 (50 microg) was administered intrathecally 10 min before paw formalin injection or intrathecal gabapentin. The paw flinch numbers in 1 min were counted at the first minute and every 5 min for 1 h after formalin injection. RESULTS: Biphasic flinching responses were induced by formalin and monitored at 0-9 min (phase 1) and 10-60 min (phase 2) after formalin injection. Gabapentin (100 and 200 microg), given intrathecally 10 min before formalin injection, attenuated the flinching response during phase 2 of the formalin test. ZD7288 (50 microg), given intrathecally 10 min before formalin injection or intrathecal gabapentin injection, did not attenuate the formalin-induced flinching response or reverse gabapentin-induced analgesia. CONCLUSION: Our data suggest that activation of spinal or dorsal root ganglion HCN channels or both is not involved in formalin-induced pain, and intrathecal gabapentin does not act as an HCN channel activator to achieve its antinociceptive effect in the formalin test.

Chronic intrathecal infusion of minocycline prevents the development of spinal-nerve ligation-induced pain in rats.

BACKGROUND AND OBJECTIVES: Minocycline is a second-generation tetracycline with multiple biological effects, including inhibition of microglial activation. Recently, microglial activation has been implicated in the development of nerve injury-induced neuropathic pain. In this study, the authors examined the effects of continuous intrathecal minocycline on the development of neuropathic pain and microglial activation induced by L5/6 spinal-nerve ligation in rats. METHODS: Under isoflurane anesthesia, male Sprague-Dawley rats (200-250 g) received right L5/6 spinal-nerve ligation and intrathecal catheters connected to an infusion pump. Intrathecal saline or minocycline (2 and 6 microg/h) was given continuously after surgery for 7 days (n = 8 per group). The rat right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before surgery and on days 1 to 7 after surgery. Spinal microglial activation was evaluated with OX-42 immunoreactivity on day 7 after surgery. RESULTS: Spinal-nerve ligation induced mechanical allodynia and thermal hyperalgesia on the affected hind paw of saline-treated rats. Intrathecal minocycline (2 and 6 microg/h) prevented the development of mechanical allodynia and thermal hyperalgesia induced by nerve ligation. It also inhibited nerve ligation-induced microglial activation, as evidenced by decreased OX-42 staining. No obvious histopathologic change was noted after intrathecal minocycline (6 microg/h) infusion. CONCLUSIONS: In this study, the authors demonstrate the preventive effect of continuous intrathecal minocycline on the development of nociceptive behaviors induced by L5/6 spinal-nerve ligation in rats. Further studies are required to examine if continuous intrathecal minocycline could be used safely in the clinical setting.

Rigid ventilation bronchoscopy under general anesthesia for treatment of pediatric pulmonary atelectasis caused by pneumonia: A review of 33 cases.

Pediatric pulmonary atelectasis caused by pneumonia is a common disease. If the mucus plugs or secretions occlude the bronchial trees and cannot be cleaned by coughing, suctioning, or vigorous respiratory and physical therapy, is rigid ventilation bronchoscopy (V-B) effective and safe as a therapeutic procedure in such patients? We collected 33 cases of pediatric pulmonary atelectasis that were treated by rigid V-B under general anesthesia for removal of the mucus plugs or foreign bodies. During the rigid V-B with lung lavage performed by experienced bronchoscopists, the oxygen saturation was maintained in good condition. No disastrous complications were noted. Sixty-four percent (21/33) of those with pediatric pulmonary atelectasis had significant improvement in either oxygen saturation or chest radiography within 72 hours. We conclude that when the traditional treatment in pediatric pulmonary atelectasis was ineffective, rigid V-B might be an adequate and safe procedure to remove the mucus plugs and restore pulmonary function.

Protection by hot water extract of Panax notoginseng on chronic ethanol-induced hepatotoxicity.

The purpose of this study was to investigate the antioxidant effects of a hot water extract of Panax notoginseng (PNG) against chronic ethanol-induced hepatotoxicity. Fifty mice were divided into fi ve equal groups with 10 in each group. Group 1 (control) received saline, whereas group 2 received ethanol (70%, 0.1 mL, p.o.) once daily for 4 weeks, which induced hepatotoxicity, manifested biochemically by a significant elevation of serum enzyme activities, such as SGOT and SGPT. Hepatotoxicity was further evidenced by a significant increase in the hepatic lipid peroxidation measured. Groups 3-5 were administered a hot water extract of PNG at doses of 10, 25 and 50 mg/kg 2 weeks after initiating oral administration of ethanol, for a further 2 weeks. PNG ameliorated the rise in serum sGOT and sGPT induced by chronic ethanol administration. The mice were killed after PNG administration. In a separate study, PNG inhibited the lipid peroxidation in the mouse liver homogenate induced by ethanol in a dose-dependent manner. The findings indicate that PNG is an efficient cytoprotective agent against chronic ethanol-induced hepatotoxicity, possibly through inhibition of the production of oxygen-free radicals that cause lipid peroxidation.

Bronchoscopy and anesthesia for preschool-aged patients: a review of 228 cases.

Pediatric bronchoscopy is a complicated, high-risk procedure. From May 2000 to May 2002, we performed bronchoscopy in 228 preschool-aged children (newborn to 6 years old) under general anesthesia with a Storz-Hopkins rigid pediatric bronchoscope. The final diagnosis and complications during anesthesia were recorded. The most common findings from bronchoscopic examination were subglottic stenosis (or granuloma) (67, 29.4%), laryngomalacia (64, 28.1%), tracheal stenosis (or malacia) (29, 12.7%), pneumonia (23, 10.1%), and atelectasis (16, 7.0%). The main complications during anesthesia were arrhythmias, oxygen desaturation, and CO2 retention (high end-tidal CO2). The most serious complication was pneumothorax in one patient. Either endotracheal intubation or tracheostomy was required in 61% of the patients in this series to secure a patent airway after bronchoscopy. Bronchoscopy is necessary as a diagnostic and therapeutic tool for certain airway diseases or anomalies in pediatric patients. It requires cooperation between the endoscopist and anesthesiologist to insure the patient's safety.