Electrophysiological evidence for tetrodotoxin-resistant sodium channels in slowly conducting dural sensory fibers.
A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small diameter neurons of peripheral sensory ganglia. The peripheral axons of sensory neurons appear to lack this channel, but its presence has not been investigated in peripheral nerve endings, the site of sensory transduction in vivo. We investigated the effect of TTX on mechanoresponsiveness in nerve endings of sensory neurons that innervate the intracranial dura. Because the degree of TTX resistance of axonal branches could potentially be affected by factors other than channel subtype, the neurons were also tested for sensitivity to lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium channels. Single-unit activity was recorded from dural afferent neurons in the trigeminal ganglion of urethan-anesthetized rats. Response thresholds to mechanical stimulation of the dura were determined with von Frey monofilaments while exposing the dura to progressively increasing concentrations of TTX or lidocaine. Neurons with slowly conducting axons were relatively resistant to TTX. Application of 1 microM TTX produced complete suppression of mechanoresponsiveness in all (11/11) fast A-delta units [conduction velocity (c.v.) 5-18 m/s] but only 50% (5/10) of slow A-delta units (1.5 +info)
RINm5f cells express inactivating BK channels whereas HIT cells express noninactivating BK channels.
Large-conductance Ca2+- and voltage-activated BK-type K+ channels are expressed abundantly in normal rat pancreatic islet cells and in the clonal rat insulinoma tumor (RINm5f) and hamster insulinoma tumor (HIT) beta cell lines. Previous work has suggested that the Ca2+ sensitivity of BK channels in RIN cells is substantially less than that in HIT cells, perhaps contributing to differences between the cell lines in responsiveness to glucose in mediating insulin secretion. In both RIN cells and normal pancreatic beta cells, BK channels are thought to play a limited role in responses of beta cells to secretagogues and in the electrical activity of beta cells. Here we examine in detail the properties of BK channels in RIN and HIT cells using inside-out patches and whole cell recordings. BK channels in RIN cells exhibit rapid inactivation that results in an anomalous steady-state Ca2+ dependence of activation. In contrast, BK channels in HIT cells exhibit the more usual noninactivating behavior. When BK inactivation is taken into account, the Ca2+ and voltage dependence of activation of BK channels in RIN and HIT cells is essentially indistinguishable. The properties of BK channel inactivation in RIN cells are similar to those of inactivating BK channels (termed BKi channels) previously identified in rat chromaffin cells. Inactivation involves multiple, trypsin-sensitive cytosolic domains and exhibits a dependence on Ca2+ and voltage that appears to arise from coupling to channel activation. In addition, the rates of inactivation onset and recovery are similar to that of BKi channels in chromaffin cells. The charybdotoxin (CTX) sensitivity of BKi currents is somewhat less than that of the noninactivating BK variant. Action potential voltage-clamp waveforms indicate that BK current is activated only weakly by Ca2+ influx in RIN cells but more strongly activated in HIT cells even when Ca2+ current magnitude is comparable. Concentrations of CTX sufficient to block BKi current in RIN cells have no effect on action potential activity initiated by glucose or DC injection. Despite its abundant expression in RIN cells, BKi current appears to play little role in action potential activity initiated by glucose or DC injection in RIN cells, but BK current may play an important role in action potential repolarization in HIT cells. (+info)
Comparison of local anesthetic activities between optical isomers of cis-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene.
The optical isomers of cis-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene (YAU-17) were compared for their local anesthetic activity, acute toxicity, spasmolytic activity, and partition coefficient between chloroform and phosphate buffer. 1-YAU-17 was more active than d-YAU-17 in blocking the conduction of action potentials in isolated frog sciatic nerves. The difference in local anesthetic activities between the optical isomers was further substantiated by in vivo tests for corneal anesthesia, intracutaneous anesthesia and sciatic nerve block in quinea-pigs. Similarly, the i.v. injection to mice revealed a higher toxicity for 1-YAU-17 as compared to its d-isomer. In these tests, the potency ratios of the enantiomers ranged from 2 to 4, and the racemate had an intermediate potency. On the contrary, no difference among the compounds was found in their liposolubility, partition coefficient, and spasmolytic activity examined with isolated guinea-pig ileum. These results indicate that the steric factors play an important role in the production of different local anesthetic activities between the optical isomers of YAU-17, and their local anesthetic potency tends to be correlated to their intravenous acute toxicity but not to their spasmolytic activity. (+info)
Pharmacological studies on root bark of mulberry tree (Morus alba L.)
Pharmacological studies were done on the root bark of mulberry tree and pharmacological effects were compared with the clinical effects of "Sohakuhi" in Chinese medicine. n-Butanol- and water-soluble fractions of mulberry root had similar effects except for those on the cadiovascular system. Both fractions showed cathartic, analgesic, diuretic, antitussive, antiedema, sedative, anticonvulsant, and hypotensive actions in mice, rats, guinea pigs and dogs. There appears to be a correlation between the experimental pharmacological results and the clinical applications of mulberry root found in the literature on Chinese medicine. (+info)
Evaluation of lidocaine as an analgesic when added to hypertonic saline for sclerotherapy.
PURPOSE: The efficacy of sclerosing agents for the treatment of telangiectasias and reticular veins is well established. The injection of these agents is often associated with pain, and it is not uncommon for sclerotherapists to include lidocaine with the sclerosants in an attempt to reduce the pain associated with treatment. However, there are concerns that this may reduce the overall efficacy of the treatment because of dilution of the sclerosant. Patient comfort and overall outcome associated with treatment using HS with lidocaine (LIDO) versus that using HS alone was compared. METHODS: Forty-two patients were prospectively entered into the study and randomized blindly to sclerotherapy with 23.4% HS or 19% LIDO. Study subjects and treating physicians were blinded to the injection solution used. Injection sites were chosen for veins ranging in size from 0.1 to 3 mm. Photographs of the area to be treated were taken, and the patients rated their pain. They were then observed at regular intervals for four months, and clinical data was collected. Thirty-five subjects completed the full follow-up period, and photographs of the injected area were taken again. Three investigators blinded to the treatment assignment then evaluated the photographs and scored the treatment efficacy according to a standardized system. RESULTS: In the HS group, 61.9% (13 of 21) patients rated their pain as none or mild, whereas 90.5% (19 of 21) of patients in the LIDO group had no or mild discomfort. This difference is significant, with a P value of.034. There was no difference in the overall efficacy of treatment between the two groups. The groups had similar rates of vein thrombosis and skin necrosis. CONCLUSION: Although lidocaine is often used with sclerosing agents, there are no previous reports in the literature to evaluate its effectiveness in reducing the pain experienced by the patient. In this study, patients receiving LIDO experienced significantly less discomfort at the time of injection than patients who received HS alone. There were no differences in the effectiveness of treatment or in the incidence of complications between the two groups. (+info)
A study of local anaesthetics. Part 148. Influence of auxiliary substances on the surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII.
The influence of auxiliary substances of the polyol group (glycerol, propylene glycol, sorbitol) and of their concentration (5, 10, 15 and 20% by weight) upon surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII, viz., N-[2-(2-propoxyphenylcarbamoyloxy)-ethyl] piperidinium chloride was studied. The substances were applied as hydrogel humectants. It was found that their influence on the surface tension, distribution coefficient and pharmaceutical availability from solutions of the potential drug VII depended on the type as well as concentration of the auxiliary substance. From the viewpoints of use in formulations of the drug form, sorbitol used at 5 and 10% concentrations represented the optimum. (+info)
Dose-response effects of spinal neostigmine added to bupivacaine spinal anesthesia in volunteers.
BACKGROUND: Intrathecal adjuncts often are used to enhance small-dose spinal bupivacaine for ambulatory anesthesia. Neostigmine is a novel spinal analgesic that could be a useful adjunct, but no data exist to assess the effects of neostigmine on small-dose bupivacaine spinal anesthesia. METHODS: Eighteen volunteers received two bupivacaine spinal anesthetics (7.5 mg) in a randomized, double-blinded, crossover design. Dextrose, 5% (1 ml), was added to one spinal infusion and 6.25, 12.5, or 50 microg neostigmine in dextrose, 5%, was added to the other spinal. Sensory block was assessed with pinprick; by the duration of tolerance to electric stimulation equivalent to surgical incision at the pubis, knee, and ankle; and by the duration of tolerance to thigh tourniquet. Motor block at the quadriceps was assessed with surface electromyography. Side effects (nausea, vomiting, pruritus, and sedation) were noted. Hemodynamic and respiratory parameters were recorded every 5 min. Dose-response relations were assessed with analysis of variance, paired t tests, or Spearman rank correlation. RESULTS: The addition of 50 microg neostigmine significantly increased the duration of sensory and motor block and the time until discharge criteria were achieved. The addition of neostigmine produced dose-dependent nausea (33-67%) and vomiting (17-50%). Neostigmine at these doses had no effect on hemodynamic or respiratory parameters. CONCLUSIONS: The addition of 50 microg neostigmine prolonged the duration of sensory and motor block. However, high incidences of side effects and delayed recovery from anesthesia with the addition of 6.25 to 50 microg neostigmine may limit the clinical use of these doses for outpatient spinal anesthesia. (+info)
Comparison of three solutions of ropivacaine/fentanyl for postoperative patient-controlled epidural analgesia.
BACKGROUND: Ropivacaine, 0.2%, is a new local anesthetic approved for epidural analgesia. The addition of 4 microg/ml fentanyl improves analgesia from epidural ropivacaine. Use of a lower concentration of ropivacaine-fentanyl may further improve analgesia or decrease side effects. METHODS: Thirty patients undergoing lower abdominal surgery were randomized in a double-blinded manner to receive one of three solutions: 0.2% ropivacaine-4 microg fentanyl 0.1% ropivacaine-2 microg fentanyl, or 0.05% ropivacaine-1 microg fentanyl for patient-controlled epidural analgesia after standardized combined epidural and general anesthesia. Patient-controlled epidural analgesia settings and adjustments for the three solutions were standardized to deliver equivalent drug doses. Pain scores (rest, cough, and ambulation), side effects (nausea, pruritus, sedation, motor block, hypotension, and orthostasis), and patient-controlled epidural analgesia consumption were measured for 48 h. RESULTS: All three solutions produced equivalent analgesia. Motor block was significantly more common (30 vs. 0%) and more intense with the 0.2% ropivacaine-4 microg fentanyl solution. Other side effects were equivalent between solutions and mild in severity. A significantly smaller volume of 0.2% ropivacaine-4 microg fentanyl solution was used, whereas the 0.1% ropivacaine-2 microg fentanyl group used a significantly greater amount of ropivacaine and fentanyl. CONCLUSIONS: Lesser concentrations of ropivacaine and fentanyl provide comparable analgesia with less motor block despite the use of similar amounts of ropivacaine and fentanyl. This finding suggests that concentration of local anesthetic solution at low doses is a primary determinant of motor block with patient-controlled epidural analgesia after lower abdominal surgery. (+info)