Methods: Inflammatory pain was induced by a burn (at 47 [degree sign]C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100).
Results: The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P
Methods: After institutional approval and informed patient consent were obtained, 60 patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and any adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing "the worst possible pain" was introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime. The morphine regimen was adjusted individually to a maximal oral dose of 80-90 mg/day to keep the visual analog scale score less than 4. When patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dipyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption when the test drug was introduced to keep their visual analog scale score less than 4.
Results: The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced were similar among the groups. The daily consumption of oral morphine was as follows: on day 15: CG = DG = NG (P > 0.05), CG > KG (P = 0.036); on day 20: CG > NG = KG (P < 0.02) (CG > KG, P < 0.005; CG > NG, P < 0.02), DG > KG (P < 0.05); on day 30: CG = DG > KG = NG (P < 0.05). Patients in the CG and DG groups reported somnolence, but patients in the NG and KG groups did not. 相似文献
Methods: Male Sprague-Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive threshold. The analgesic effects of intrathecal or intraperitoneal ketamine were examined in the rats that received unilateral intraplantar carrageenan and in those that were untreated. In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine. Using an intrathecal microdialysis method, noradrenaline and 5-hydroxytryptamine concentrations in lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both saline- and carrageenan-treated rats.
Results: In the untreated rats, intraperitoneal but not intrathecal ketamine produced antinociceptive effects in a dose-dependent manner. Pretreatment with intrathecal yohimbine or methysergide inhibited these antinociceptive effects. Intraplantar carrageenan significantly reduced paw withdrawal latencies on the injected paw but not on the contralateral paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw withdrawal latencies on the injected side in a dose-dependent manner without any effects on the contralateral side. Neither yohimbine nor methysergide inhibited these antihyperalgesic effects. In analyses of monoamines, the magnitude of increase in monoamines after intraperitoneal ketamine was significantly smaller in the carrageenan-treated rats than in the saline-treated rats. 相似文献
Methods: Thirty children, 9-19 yr of age, scheduled for spinal fusion, were randomly allocated into three groups to receive a single dose of 0 (saline injection), 2, or 5 [mu]g/kg intrathecal morphine. After surgery, a patient-controlled analgesia device (PCA) provided free access to additional intravenous morphine. Children were monitored for 24 h in the postanesthesia care unit.
Results: The three groups were similar for age, weight, duration of surgery, and time to extubation. The time to first PCA demand was dose-dependently delayed by intrathecal morphine. The first 24 h of PCA morphine consumption was 49 +/- 17, 19 +/- 10, and 12 +/- 12 mg (mean +/- SD) in the saline, 2 [mu]g/kg morphine, and 5 [mu]g/kg morphine groups, respectively. Pain scores at rest were significantly lower over the whole study period after 2 and 5 [mu]g/kg intrathecal morphine than after saline, but there was no difference between intrathecal doses. Pain scores while coughing and the incidence of side effects were similar in the three groups. 相似文献
Methods: Gastrectomy patients were given preemptive analgesia consisting of epidural morphine, intravenous low-dose ketamine, and combinations of these in a randomized, double-blind manner. Postsurgical pain intensity was rated by a visual analog scale, a categoric pain evaluation, and cumulative morphine consumption.
Results: Preemptive analgesia by epidural morphine and by intravenous low-dose ketamine were significantly effective but not definitive. With epidural morphine, a significant reduction in visual analog scale scores at rest was observed at 24 and 48 h, and morphine consumption was significantly lower at 6 and 12 h, compared with control values. With intravenous ketamine, visual analog scale scores at rest and morphine consumption were significantly lower at 6, 12, 24, and 48 h than those in control subjects. The combination of epidural morphine and intravenous ketamine provided definitive preemptive analgesia: Visual analog scale scores at rest and morphine consumption were significantly the lowest at 6, 12, 24, and 48 h, and the visual analog scale score during movement and the categoric pain score also were significantly the lowest among the groups. 相似文献
Methods: The increase of electrical, heat, and pressure pain tolerance and the decrease of ice-water and ischemic pain perception was determined at baseline and at four different plasma concentrations of alfentanil (n = 7) administered as target controlled infusion or placebo (n = 7). A linear mixed-effects modeling (NONMEM) was performed to detect drug, placebo, and time effect as well as interindividual and intraindividual variation of effect.
Results: Only the electrical, ice-water, and pressure pain tests are sensitive to assess a concentration-response curve of alfentanil. At a plasma alfentanil concentration of 100 ng/ml, the increase in pain tolerance compared with baseline was 42.0% for electrical pain, 22.2% for pressure pain, and 21.7% for ice-water pain. The slope of the linear concentration-response curve had an interindividual coefficient of variation of 58.3% in electrical pain, 35.6% in pressure pain, and 60.0% in ice-water pain. The residual error including intraindividual variation at an alfentanil concentration of 100 ng/ml was 19.4% for electrical pain, 6.1% for pressure pain, and 13.0% for ice-water pain. Electrical pain was affected by a significant placebo effect, and pressure pain was affected by a significant time effect. 相似文献
Methods: Ketamine was administered to eight healthy volunteers with use of a target-controlled infusion to three predicted plasma concentrations: 0 (saline), 50 (subanalgesic), and 200 ng/ml (analgesic, subanesthetic). Volunteers received noxious thermal stimuli and auditory stimuli and performed a motor task within a 3-T human brain imaging magnet. Activation of brain regions in response to noxious and auditory stimuli and during the motor task was compared with behavioral measures.
Results: The analgesic subanesthetic dose of ketamine significantly reduced the pain scores, and this matched a decrease in activity within brain regions that activate in response to noxious stimuli, in particular, the insular cortex and thalamus. A different pattern of activation was observed in response to an auditory task. In comparison, smaller behavioral and imaging changes were found for the motor paradigm. The lower dose of ketamine gave similar but smaller nonsignificant effects. 相似文献
Methods: Mechanical hyperalgesia was assessed with the paw-pressure test in mononeuropathic (chronic constrictive injury model) and diabetic rats. Behavioral reactions were scored in a model of inflammation induced by formalin. The animals were assigned to one of three groups according to the intraperitoneal pretreatment: magnesium (30 mg/kg x 3), magnesium (30 mg/kg), and saline. Before testing, morphine was injected intravenously in mononeuropathic (0.3 mg/kg) and diabetic rats (1 mg/kg) and by the subcutaneous route in rats with the formalin test (1.5 mg/kg).
Results: Magnesium alone induced a significant antihyperalgesic effect in mononeuropathic and diabetic rats after a cumulative dose of 90 mg/kg. Furthermore, it significantly increased morphine analgesia, regardless of the loading dose used (30 or 90 mg/kg) in the two models of neuropathic pain. In the formalin test, magnesium alone did not have a significant effect. However, in combination with morphine, it revealed the analgesic effect of this opiate. 相似文献
Methods: Twenty patients participated in two randomized, double-blinded, placebo-controlled, crossover experiments in which they, on four different days, received a 30-minute intravenous infusion of ketamine (0.24 mg/kg), lidocaine (5 mg/kg), or saline. Ongoing pain, pain evoked by brush and repetitive pinprick stimuli, and acetone was measured before, during, and after infusion.
Results: Ketamine significantly reduced ongoing pain and evoked pain to brush and pinprick, whereas lidocaine only reduced evoked pain to repetitive pinprick stimuli. In individual patients, there was no correlation between the pain-relieving effect of lidocaine and ketamine on ongoing or mechanically evoked pains. 相似文献
Methods: Twenty patients were studied. The burn injury was induced 6 days before surgery with a contact thermode (12.5 cm2, 47[degrees]C for 7 min). The sensory testing, before and 1 h after the injury, included pain score during induction of the burn, secondary hyperalgesia area, thermal and mechanical pain perception, and pain thresholds. Postoperative analgesia consisted of ibuprofen and acetaminophen. Pain ratings (visual analog scale) at rest and during limb movement were followed for 10 days after surgery.
Results: The burn injury was associated with development of significant hyperalgesia. There was a significant correlation between preoperative pain ratings during the burn injury and early (0-2 days, area under the curve) and late (3-10 days, area under the curve) postoperative dynamic pain ratings during limb movement. 相似文献