Inhibition of spinal protein kinase C blocks substance P-mediated hyperalgesia.

Substance P (SP) is an important neuromediator in the spinal processing of nociceptive afferent information. Our previous study has shown that spinal (intrathecal, IT) application of SP produces thermal hyperalgesia that is mediated by activation of the G-protein coupled NK1 receptor. The activation of some classes of the G-protein coupled receptors is known to produce diacylglycerol with consequent activation of protein kinase C (PKC). In the present study, we have demonstrated that intrathecal administration of a selective PKC inhibitor GF109203X (GF, 0.73 nmol) in rats chronically implanted with intrathecal catheters 15 min prior to IT-SP (48 nmol) completely blocked the SP-induced thermal hyperalgesia. The effect of GF was dose-dependent (0.073-0.73 nmol). Bisindolymaleimide V, the inactive homolog of GF, had no effect. Pretreatment with GF 3 h, but not 24 h, prior to SP still produced antinociception. Moreover, intrathecal treatment with GF (0.73 nmol) attenuated the formalin paw injection-induced flinching, preferentially at the 2nd phase, that is known to be associated with the release of endogenous SP at the spinal cord. These data suggest that activation of spinal PKC is involved in the SP-mediated hyperalgesia. Thus, SP, which is released in the spinal cord subsequent to persistent stimulation of small sensory afferents after tissue injury, may contribute to spinal hyperexcitability and persistent pain by enhancement of PKC-mediated phosphorylation of target molecules such as NMDA receptors.

Severe lightning pain after subarachnoid block in a patient with neuropathic pain of central origin: which drug is best to treat the pain?

OBJECTIVE: There have been many reports that spinal anesthesia induces severe lightning pain in the lower limbs of patients with phantom limb pain, tabes dorsalis, or causalgia. We report on a patient with neuropathic pain of central origin who showed newly developed severe lightning pain after therapeutic subarachnoid block (SAB). We performed SAB 16 times in this patient, and he complained of severe pain each time. We investigated which drug was best for treating such induced pain by administering various drugs to the patient. SETTING: The patient was hospitalized for treatment and observation. PATIENT: The patient was a 48-year-old man with neuropathic pain secondary to an incomplete spinal cord injury at the cervical segment. INTERVENTIONS: Various drugs were administered for relieving the newly developed severe pain, and the effectiveness of these agents was compared. RESULTS AND CONCLUSIONS: Intravenous thiopental, fentanyl, butorphanol, ketamine, midazolam, droperidol, and sevoflurane-oxygen anesthesia were quite effective. Intramuscular butorphanol was not effective. Intravenous physiologic saline and atropine sulfate as a placebo, intrathecal morphine hydrochloride, intravenous mexiletine, and lidocaine were ineffective. Intravenous thiopental (approximately 1 mg/kg) was thought to obtain the best pain relief because it stopped the pain quickly, the dose needed was subanesthetic, and there was no adverse effect.

[Linear polarized light irradiation around the stellate ganglion area increases skin temperature and blood flow].

We evaluated the effect of linear polarized light irradiation with a SUPER LIZER around the stellate ganglion area on skin temperature and blood flow in healthy adult volunteers. We carried out two experiments (study I and study II). In study I, we investigated one-sided irradiation around the stellate ganglion area or posterior neck on the skin temperature of the bilateral nasus externi and earlobes. In study II, we investigated one-sided irradiation around the stellate ganglion area or posterior neck on the skin temperatures of both hands and skin blood flow on the irradiated side. In study I, irradiation around the stellate ganglion area increased skin temperature on the irradiated sides of the nasus externi (wings of the nose), and in study II, skin temperature and blood flow were increased on the irradiated side of the hands. These results suggest that linear polarized light irradiation with a SUPER LIZER around the stellate ganglion area would be useful and beneficial in clinical therapy.

[A case of using continuous double-tapped epidural analgesia for herpes zoster duplex].

A 66-year-old woman developed herpes zoster duplex, which is a rare disease. She had severe pain at the right upper back area and left lower abdominal area. The authors used double-tapped continuous epidural analgesia for this patient. The catheters for the epidural block were placed at the 8th thoracic vertebral level and 2nd lumbar vertebral level. After the start of continuous epidural block, she suffered from nausea, vomited, and felt dizzy. It was evident that these symptoms were caused by local anesthetic toxicity. We emphasize that we must pay attention to the patient who undergoes continuous double-tapped epidural analgesia for pain relief so as not to elicit local anesthetic toxicity.

[The effects of intravenous lidocaine on baroreflex control of heart rate in man].

The effects of intravenous lidocaine on arterial baroreflex control of heart rate were investigated using both the pressor and depressor tests in 16 adult patients. Baroreflex sensitivity was unchanged 5 and 20 minutes after lidocaine 1.5 mg.kg-1 bolus injection according to the results of both the pressor and depressor tests. Resetting of the baroreflex, tachycardia and increased blood pressure were also observed after lidocaine injection. Clinically the results obtained in the present study suggest that it is safe to use lidocaine even when reduction of blood pressure by hypovolemia or declamping the main artery is expected and when a rise in blood pressure due to cross-clamping of the main artery is foreseen. However, intravenous lidocaine tended to produce tachycardia, and baroreflex sensitivity was unchanged after lidocaine injection according to the results of the depressor test. This means that tachycardia readily occurs during hypotension. This may suggest that intravenous lidocaine is not always advantageous for patients with ischemic heart disease.

[Changes in dementia rating scale scores of elderly patients with femoral neck fracture during perioperative period].

We evaluated changes in dementia rating scale scores in the revised version of Hasegawa's dementia scale (HDS-R), and rated dementia, 2 days before and 7 days after surgery in the elderly patients with femoral neck fracture. The 50 patients examined ranged in age from 70 years to 101 years. A perfect score in the HDS-R is 30 points, and a score below 20 points strongly suggests dementia. The results were as follows. In septuagenarian and octogenarian patients, the scale score was higher after surgery than the value before the surgery. Although the preoperative and postoperative scores of the patients who had been under epidural anesthesia were not significantly different, the score of patients who had been under general anesthesia was higher in the postoperative period than in the preoperative period. In octogenarian patients, there was a negative correlation between "postoperative score minus preoperative score" and "the number of the days from suffering fracture to surgery". These results showed that general anesthesia is more advantageous than epidural anesthesia from the viewpoint of the intellectual faculty in septuagenarian and octogenarian patients with femoral neck fracture, and it is within the bounds of possibility that the intellectual faculty may decline if an octogenarian patient is operated after a long delay from the occurrence of fracture. To prevent this decline, patients must be operated on as soon as possible.

[A case of atopic dermatitis treated with stellate ganglion block--the change of serum IgE and blood eosinophil levels].

Stellate ganglion block (SGB) therapy was tried on a patient with severe adult type atopic dermatitis. SGB was performed 102 times in total and clinical symptoms improved gradually. Serum IgE and blood eosinophil levels, which correlate with disease severity, increased gradually following repeated SGB. After a series of SGB was stopped, clinical symptoms became worse and serum IgE and blood eosinophil levels increased again. We conclude that although SGB is presumably one of the effective therapies for severe adult type atopic dermatitis, it might be difficult to improve atopic constitution entirely because the patient was not cured completely following repeated SGB.

Effect of prophylactic bronchodilator treatment with i.v. carperitide on airway resistance and lung compliance after tracheal intubation.

BACKGROUND: Lung resistance increases after induction of anaesthesia. We hypothesized that prophylactic bronchodilation with i.v. carperitide before tracheal intubation would decrease airway resistance and increase lung compliance after placement of the tracheal tube in both smokers and nonsmokers. METHODS: Ninety-seven adults aged between 24 and 59 yr were randomized to receive i.v. normal saline (0.9% saline) (control) or carperitide, 0.2 microg kg(-1) min(-1) throughout the study. The 97 patients included smokers and nonsmokers. Thus the patients were allocated to one of the four groups: smokers who received normal saline (n=21), nonsmokers who received normal saline (n=27), smokers who received carperitide (n=19) or nonsmokers who received carperitide (n=30). Thirty minutes after starting normal saline or carperitide infusion, we administered thiamylal 5 mg kg(-1) and fentanyl 5 microg kg(-1) to induce general anaesthesia and vecuronium 0.3 mg kg(-1) for muscle relaxation. Continuous infusion of thiamylal 15 mg kg(-1) h(-1) followed anaesthetic induction. Mean airway resistance (R(awm)), expiratory airway resistance (R(awe)) and dynamic lung compliance (C(dyn)) were determined 4, 8, 12 and 16 min after tracheal intubation and compared between the four groups. RESULTS: At 4 min after intubation, R(awm) and R(awe) were higher and C(dyn) lower in smokers than in nonsmokers in the control group. R(awm) and R(awe) were lower and C(dyn) higher in smokers in the carperitide group than in smokers in the control group. R(awm) and R(awe) were lower in nonsmokers in the carperitide group than in nonsmokers in the control group. CONCLUSIONS: Marked bronchoconstriction occurred in the control groups (smokers and nonsmokers) 4 min after tracheal intubation. Prophylactic treatment with carperitide before induction of anaesthesia and tracheal intubation was advantageous, particularly in smokers.

Large dose of flunitrazepam attenuates baroreflex control of heart rate in man.

The effects of intravenous tranquilizers such as flunitrazepan, diazepam and droperidol on baroreflex control of heart rate were investigated using both pressor and depressor tests. The dose-dependency was also studied by the administration of the drugs at the usual or twofold dosage. The usual dosage caused no significant change in neuronal controlling mechanism of circulation. However, flunitrazepam at double the usual dosage produced a decrease in baroreflex sensitivity at depressor tests. The results suggest that flunitrazepam when given repeatedly might accelerate hemodynamic derangements induced by an acute decrease in blood pressure.

The effects of an intravenous nicardipine injection on baroreflex control of heart rate in man.

The effects of nicardipine injection on baroreflex control of heart rate were investigated by both pressor and depressor tests in 17 adult patients. Baroreflex sensitivity was attenuated after nicardipine injection by the pressor test using phenylephrine, whereas it was not changed by the depressor test using nitroglycerine. No resetting of the baroreflex occurred after nicardipine injection. By the pressor test, the plasma norepinephrine level was decreased, indicating that parasympathetic activity increased, and by the depressor test, the plasma norepinephrine concentration was increased, indicating that sympathetic activity increased. These results suggest that it is safe to use nicardipine clinically even when reduction in blood pressure for hypovolemia or unclamping the main artery is expected, and it is disadvantageous to administer the drug when an increase in blood pressure due to cross-clamping of the main artery is forecasted.

The effects of butorphanol on baroreflex control of heart rate in man.

The effects of butorphanol injection on baroreflex control of heart rate were investigated using both pressor and depressor tests in eighteen adult patients. Baroreflex sensitivity was attenuated after butorphanol injection in the pressor test using phenylephrine, whereas it was unchanged in the depressor test using nitroglycerine. No resetting of the baroreflex occurred after butorphanol injection. After the administration of butorphanol, plasma epinephrine and norepinephrine levels increased. These results suggest that it is safe to use butorphanol clinically even when a reduction in blood pressure due to hypovolemia or unclamping of the major artery is expected and that it is disadvantageous to administer the drug when an increase in blood pressure due to cross-clamping of the major artery is predicted.

Dobutamine infusion modifies thermoregulation during general anesthesia.

A redistribution of body heat from core to peripheral tissues causes a rapid decrease in core temperature. The present study tested whether a dobutamine infusion would facilitate redistribution and induce a further decrease in core temperature. Volunteers were randomly assigned to the control group (n = 8) and the experimental group (n = 8). They were anesthetized with isoflurane at an end-tidal concentration of near 1.2% for 120 min. In the experimental group, dobutamine was infused at a rate of 4 micrograms.kg-1.min-1. Core temperature, skin temperature, tissue temperature, and laser-Doppler perfusion index were measured. Leg heat content was calculated by morphometric data and observed temperatures. The decrease in leg heat content was larger in the control group than in the experimental group 30 min after anesthetic induction (P < 0.05). In contrast, the core temperature decreased further in the dobutamine group than in the control group 40 min after induction (P < 0.05). Dobutamine induced further hypothermia, presumably by facilitating heat transfer and by increasing cutaneous heat loss. Hypothermia will be increased when using dobutamine for anesthesia.

Propofol alone, sevoflurane alone, and combined propofol-sevoflurane anaesthesia in electroconvulsive therapy.

Electroconvulsive therapy is an effective treatment for severe and medication-resistant depression. There have been no reports describing how a volatile anaesthetic affects haemodynamic responses, seizure duration, and recovery characteristics during electroconvulsive therapy. We carried out a repeated-measure crossover study to compare the effects on haemodynamic responses, seizure duration, and recovery characteristics of the following types of anaesthesia in electroconvulsive therapy: propofol alone, sevoflurane alone, and propofol combined with sevoflurane. We recruited 50 patients requiring electroconvulsive therapy for depression. For anaesthesia induction, 1.5 mg/kg propofol (condition P), 5% sevoflurane in oxygen following a vital capacity rapid inhalation induction (condition S), or 1.5 mg/kg propofol followed by 5% sevoflurane in oxygen (condition PS) was administered. Succinylcholine 1.5 mg/kg was then given. Electrical stimulation was administered after fasciculation. Measurements were obtained before anaesthesia induction (baseline), prior to succinylcholine administration, prior to electroconvulsive therapy, and at the peak after electroconvulsive therapy. After electroconvulsive therapy, peak heart rate and peak mean arterial pressure were highest in condition S. Whereas recovery time was longest in condition PS, motor seizure duration was significantly shorter than in either condition P or S. Electroencephalographic seizure duration was significantly shorter in condition PS than in condition P and significantly shorter in condition S than in condition P. Sevoflurane anaesthesia alone is most disadvantageous in terms of haemodynamics. Propofol-sevoflurane anaesthesia is advantageous in terms of haemodynamics, but disadvantageous in terms of seizure duration and recovery time. Propofol alone is most advantageous in terms of seizure duration.

Analgesia after upper abdominal surgery using extradural administration of a fixed dose of buprenorphine in combination with lignocaine given at two infusion rates: a comparative study.

BACKGROUND: Extradural administration of combinations of local anaesthetics and opioids are frequently employed for postoperative pain relief. There is a scarcity of data on the analgesic effects of variations of the dose of local anaesthetic drug admixed to a fixed dose of opioid. METHODS: Twenty-four patients were investigated after elective upper abdominal surgery. During closure of the abdomen, 2% mepivacaine (8 ml) with buprenorphine 0.1 mg (0.5 ml) was given extradurally. After extubation, patients were randomly allocated to receive continuous extradural infusion of a fixed dose of buprenorphine (0.017 mg/h) in combination with 2% lignocaine at either 2.1 ml/h (low rate group, n = 14) or 6.3 ml/h (high rate group, n = 10). Postoperative pain at rest was assessed using visual analogue scale (VAS) scores and pain at movement by Prince Henry Pain Scale (PHPS) scores. Venous plasma lignocaine concentrations were measured. RESULTS: VAS scores at rest were similar in the two groups at 3 h postoperatively, whereas at 6-24 h postoperatively, VAS scores were higher in the low rate group than in the high rate group. PHPS scores were similar in the two groups at 3 h and at 18 h postoperatively, whereas at 6, 9, 12 and 24 h postoperatively, PHPS scores were higher in the low rate group than in the high rate group. Plasma lignocaine concentrations were higher at 23 h postoperatively in the high rate group than at 16 h in both groups, and at 23 h in the low rate group. At 3 h postoperatively, both the systolic and diastolic arterial pressures were higher in the low rate group than control values obtained on admission. Side effects were observed in one patient in the low rate group who complained of dizziness, and in one patient in the high rate group who complained of nausea. CONCLUSIONS: When added to a fixed dose of buprenorphine, continuous extradural infusion of 2% lignocaine at high rate provides better postoperative analgesia than when given at low rate without producing significant side effects.

Orally administered clonidine significantly reduces pain during injection of propofol.

We examined the analgesic effects of orally administered clonidine on pain induced by injection of propofol (Diprivan; 2,6-diisopropyl phenol). Female patients (n=81) were randomly allocated to one of two groups: oral clonidine (5.5 microg kg(-1)) followed by i.v. propofol and a control group given placebo followed by i.v. propofol. The median pain score in the group receiving clonidine, using a four-point scale (0=no pain, 1=minimal pain, 2=moderate pain, 3=severe pain) was 1 (0-2), significantly lower than in the control group [2 (1-3), median (25-75 percentiles), P<0.001].

The effects of intravenous lignocaine on haemodynamics and seizure duration during electroconvulsive therapy.

Electroconvulsive therapy (ECT) is commonly associated with acute hyperdynamic cardiovascular responses, and we hypothesize that intravenous lignocaine can blunt this response. We have measured the effect of lignocaine 1.5 mg/kg i.v. on heart rate and mean arterial pressure during electroconvulsive therapy. Furthermore, we also assessed seizure duration using both the cuff method and two-lead electroencephalography. We studied 25 patients using a randomized, double-blind, placebo-controlled crossover study design. Patients in the control group were given intravenous saline 0.075 ml/kg, and those in the lignocaine group were given intravenous lignocaine 2% 1.5 mg/kg, and this treatment was conducted one minute before intravenous propofol 1.5 mg/kg to induce unconsciousness. Succinylcholine 1.5 mg/kg was then administered intravenously and electrical stimulation was administered after fasciculation. Measurements were taken at the baseline, prior to succinycholine, prior to electroconvulsive therapy and at the peak response after electroconvulsive therapy. Intravenous lignocaine significantly reduced the increases in heart rate after electroconvulsive therapy, as compared with the placebo. The use of intravenous lignocaine was, however, associated with a remarkably shortened seizure duration. Due to the reduction in seizure duration, routine administration of intravenous lignocaine may not be advisable since it may interfere with the psychotherapeutic efficacy of electroconvulsive therapy. However, intravenous lignocaine medication for electroconvulsive therapy is potentially useful for reducing tachycardia in high-risk patients and reducing the severity of propofol injection pain in comparison with a placebo.

Epidural anesthesia with lidocaine reduces propofol injection pain.

PURPOSE: To determine whether epidural lidocaine reduces the severity of propofol injection pain compared with iv lidocaine. METHODS: A prospective, randomized double-blind clinical study was conducted in 120 female patients scheduled for elective gynecological laparotomy. A lumbar epidural catheter and an iv catheter placed in the cephalic vein of the non-dominant hand were used in all patients. Patients of the control group (Group C) were given epidural normal saline followed by iv normal saline then iv propofol. Patients of Group E were given epidural 2% lidocaine (0.08 mL.cm(-1)) followed by iv normal saline and then propofol. Patients of Group V were given epidural normal saline followed by iv 2% lidocaine (0.05 mL.kg(-1)) then propofol. Pain was scored as no pain=0, minimal pain=1, moderate pain=2, severe pain=3. RESULTS: The pain scores, in group E; 1 (0-2) and group V; 2 (0-2), were significantly lower than in group C; 2 (1-3); median (25th-75th percentile) (P <0.001). There was no difference in pain score between groups E and V The plasma lidocaine concentration 15 min after epidural lidocaine was 2.74 +/- 0.54 microg.ml(-1), compared with 1.54 +/- 0.31 microg.mL(-1) at three minutes after iv lidocaine. CONCLUSION: Epidural and iv lidocaine equally reduced the severity of propofol injection pain despite higher lidocaine plasma concentrations in epidurally administered lidocaine.

Analgesia after upper abdominal surgery with extradural buprenorphine with lidocaine.

PURPOSE: To determine whether the continuous low thoracic extradural administration of the same dose of lidocaine at low concentration with a high infusion rate or at high concentration with a low infusion rate in combination with a fixed dose of buprenorphine (0.4 mg.day-1) modifies postoperative pain relief. METHODS: Twenty-eight patients undergoing elective upper abdominal surgery were randomly allocated to one of two groups to receive lidocaine 2%--buprenorphine at a rate of 6.3 ml.hr-1 (2% group, n = 13) or lidocaine 6%-buprenorphine at a rate of 2.1 ml.hr-1 (6% group, n = 15). During suture of the peritoneum, mepivacaine 2% (8 ml) with 0.1 mg (0.5 ml) buprenorphine was infused extradurally. After extubation, the continuous extradural infusion was initiated. Patients were assessed for the level of analgesia with the 10 cm VAS score at rest and with the Prince Henry Pain Scale (PHPS) at 3, 6, 9, 12, 18, and 24 hr postoperatively. RESULTS: The visual analogue scale (VAS) scores at rest did not differ between the two groups except at 18 hr after surgery. The Prince Henry Pain Scale (PHPS) scores were not different between the two groups postoperatively. CONCLUSION: There was no difference in analgesia produced by the continuous extradural infusion of lidocaine 2%-buprenorphine at a rate of 6.3 ml.hr-1 and that of lidocaine 6%-buprenorphine at a rate of 2.1 ml.hr-1 following upper abdominal surgery.

Effects of rapid inhalation induction with sevoflurane-oxygen anesthesia on epidural pressure in humans.

In this study, we chose sevoflurane as the volatile anesthetic for rapid inhalation induction (RII) and investigated its usefulness. We also assessed how RII with sevoflurane affected epidural pressure, and compared RII with rapid intravenous induction by thiopental on epidural pressure. The results were as follows: RII with 5% sevoflurane had a shorter induction time compared with published results on RII with other volatile anesthetics like halothane and isoflurane, and was accompanied by fewer complications. When RII with sevoflurane was attempted, epidural pressure increased significantly upon exhalation to residual volume just before induction and during laryngoscopy and endotracheal intubation compared with the preinduction value. There was induction methods during laryngoscopy and endotracheal intubation. Epidural pressure measurements are reportedly useful in monitoring intracranial pressure. Consequently, in patients with increased intracranial pressure, exhaling to residual volume and increasing arterial blood pressure during laryngoscopy and endotracheal intubation should be avoided. The results of this study suggest that RII with 5% sevoflurane in itself is safe and useful, and that it is unlikely to increase intracranial pressure as compared with rapid intravenous induction by thiopental.