Intravenous lidocaine in central pain: a double-blind, placebo-controlled, psychophysical study. Dental impaction pain model as a potential tool to evaluate drugs with efficacy in neuropathic pain. A randomized double-blind crossover trial of intravenous lidocaine in the treatment of neuropathic cancer pain. Computer-controlled lidocaine infusion for the evaluation of neuropathic pain after peripheral nerve injury. Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Lidocaine test in neuralgia. Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II. Systemic lidocaine in pain due to peripheral nerve injury and predictors of response. Capacity of the clinical picture to characterize low back pain relieved by facet joint anesthesia. Proposed criteria to identify patients with painful facet joints.
To investigate the effects of systemic administration of lidocaine on different components of neuropathic central pains by quantitative sensory testing.
                The efficacy of systemic lidocaine (5 mg/kg IV over 30 minutes) was evaluated in a double-blind, placebo-controlled, and cross-over fashion, on both spontaneous ongoing pain and evoked pains (allodynia and hyperalgesia) in 16 patients with chronic poststroke (n = 6) or spinal cord injury (n = 10) related pain.
                Lidocaine was significantly superior to the placebo (saline) in reducing the intensity of spontaneous ongoing pain for up to 45 minutes after the injection: 10 of 16 patients (62.5%) receiving lidocaine showed a significant reduction in spontaneous pain, whereas only six patients showed this after the placebo. Lidocaine also significantly reduced the intensity of brush-induced allodynia and mechanical hyperalgesia, but was no better than the placebo against thermal allodynia and hyperalgesia. In general, the side effects were moderate and consisted mainly of lightheadedness (44%).
                Systemic lidocaine can induce a significant and selective reduction of several components of pain caused by CNS injuries. The observed preferential antihyperalgesic and antiallodynic effects of this drug suggest a selective central action on the mechanisms underlying these evoked pains. Intravenous lidocaine, a nonspecific Na-channel blocker, was used to assess the dental impaction model for evaluation of neuropathic pain drugs. Sixty patients, experiencing moderate or severe pain after removal of > or = 2 third molars, were randomized (2:2:1:1) to lidocaine (4 mg/kg; maximal dose 300 mg), oxycodone/acetaminophen (10/650 mg), placebo, and active placebo (diphenhydramine, 50 mg). Lidocaine provided a modest degree of pain relief. Predefined endpoints of total pain relief and sum of pain intensity at 2, 4, and 6 hours showed numerically, not statistically significantly, greater pain relief versus placebo. A significantly greater effect over placebo was observed in peak effect and at shorter time points (30 minutes and 1 hour), consistent with the pharmacokinetic profile (plasma concentration of approximately 2 mug/mL). Oxycodone/acetaminophen provided significantly greater analgesia versus placebo, validating study conduct, and significantly greater pain relief was observed versus lidocaine, which is consistent with a smaller portion of dental extraction pain being of neuropathic origin. In a randomized, double-blind, crossover study, we evaluated the effect of intravenous lidocaine (5 mg/kg body weight over 30 min) on the neuropathic pain of advanced cancer patients. Pain intensity, assessed by a visual analogue scale, did not show any significant difference between lidocaine and placebo infusion. The blinded choice of patients and investigators also suggested no significant improvement from lidocaine when given by this regimen. Intravenous lidocaine does not appear to have a significant analgesic effect on neuropathic cancer pain. Systemic lidocaine has been reported to be effective in treating several neuropathic pain syndromes. Few reports relate plasma lidocaine concentration to analgesia and the available studies have been complicated by labile plasma lidocaine concentrations. We used a computer-controlled infusion pump (CCIP) to target and maintain stable plasma lidocaine concentrations and study the effect of intravenous lidocaine on (1) pain scores, (2) current perception thresholds, (3) side effects, and (4) pain distribution in patients suffering from peripheral nerve injury pain.
                This study used a randomized double-blind placebo-controlled design. Eleven patients suffering from neuropathic pain after peripheral nerve injury received both a lidocaine and saline infusion in separate study sessions. The order of the study sessions was randomized and separated from each other by 1 week. The CCIP was programmed to target plasma lidocaine concentrations of 0.5, 1, 1.5, 2, and 2.5 micrograms/ml, each held for 10 min. Pain scores and pain distribution were assessed in the painful area, and electrical current perception thresholds (CPT) of the ring finger were measured using a cutaneous perception threshold neurometer (Neurometer CPT, Neurotron, Baltimore, MD). Side effects were recorded at fixed intervals. Plasma lidocaine concentrations were measured at 4 and 9 min after each step increase in infusion and correlated with the observed effects.
                Saline infusion had no effect. However, with lidocaine there was a significant plasma concentration-dependent decrease in pain scores starting at 1.5 micrograms/ml. This effect typically corresponded with a decrease in the size of the receptive field to which the pain was referred. For the electrical stimulus, there was no significant effect on cutaneous perception at 2000-Hz stimulation at the highest concentration examined; however, there was a significant increase in thresholds at 250-Hz (starting at 1.5 micrograms/ml) and 5-Hz (starting at 1.0 micrograms/ml) stimulation. There were no serious side effects. In all, 54.5% of patients reported lightheadedness (average plasma lidocaine concentration: 1.5 micrograms/ml) and one patient reported nausea (2.3 micrograms/ml).
                The computer-controlled delivery of intravenous lidocaine results in relatively stable plasma concentrations which allows a more thorough evaluation of the relationship between plasma concentration and patient response. This administration methodology for intravenous lidocaine may prove to be a valuable clinical and research tool. We studied the analgesic efficacy of an intravenous infusion of lidocaine and morphine in 19 adults with well-established postherpetic neuralgia in a three-session, randomized, double-blind, placebo-controlled trial. Compared with saline placebo, both lidocaine and morphine reduced pain intensity. Reductions in pain did not correlate with side effects produced by the infusions. For morphine, there was a significant correlation between reductions in pain intensity and blood level achieved. In the majority of subjects who reported definite pain relief, allodynia also disappeared. The results show that neuropathic pain can respond to opioids and to systemically administered local anesthetic drugs. Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables. The variables assessed were the subjective magnitude of pain, area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia. The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain. It was found that spontaneous pain and mechanical hyperalgesia were consistently improved, transiently, by intravenous administration of lidocaine in all 10 patients; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently. Spontaneous pain and mechanical hyperalgesia, but not hypoesthesia, were transiently improved by injection of saline in only 1 of the 10 patients. This outcome is probably due to a placebo effect. This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia. Thus, intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury. The transient pain relief may allow a fuller identification of the area of sensory loss. Several lines of evidence suggest that neuropathic pain (including Complex Regional Pain Syndrome [CRPS] I and CRPS II) is mediated in part by an increase in the density of voltage-sensitive sodium channels in injured axons and the dorsal root ganglion of injured axons. This study sought to characterize the effects of intravenous lidocaine (a sodium channel blocker) on acute sensory thresholds within the painful area and the size of the painful area in patients suffering from CRPS I and II.
                This study used a randomized, double-blind, placebo-controlled design in 16 subjects suffering from CRPS I and II with a prominent allodynia. Each subject received an intravenous infusion of lidocaine and diphenhydramine separated by 1 week. A computer-controlled infusion pump targeted stair-step increases in plasma levels of lidocaine of 1, 2, and 3 microg/ml. At baseline and at each plasma level, spontaneous and evoked pain scores and neurosensory testing within the painful area were measured. The neurosensory testing consisted of thermal thresholds, tactile thresholds and the area of allodynia to punctate, and stroking and thermal stimuli.
                Intravenous lidocaine and diphenhydramine had no significant effect on the cool, warm, or cold pain thresholds. However, lidocaine caused a significant elevation of the hot pain thresholds in the painful area. Intravenous lidocaine caused a significantly decreased response to stroking and cool stimuli in the allodynic area. There was also a significant decrease in pain scores to cool stimuli at all plasma levels and the spontaneous pain at the highest plasma level.
                This study demonstrates that intravenous lidocaine affects pain in response to cool stimuli more than mechanical pain in subjects with neuropathic pain. There is a lesser effect on spontaneous pain and pain induced by stroking stimuli and no effect on the pain induced by punctate stimuli. To investigate the effects of IV lidocaine on spontaneous and evoked pain (allodynia and hyperalgesia) due to peripheral nerve injury (postherpetic neuralgia or nerve trauma) using quantitative sensory testing.
                The authors randomized 22 patients to receive lidocaine 5 mg/kg IV during 30 minutes or placebo in a double-blind crossover design and 16 patients subsequently received mexiletine on an open basis titrated from 400 to 1,000 mg per day (mean 737 mg/day).
                Lidocaine induced a significant decrease in ongoing pain for up to 6 hours with a peak effect 60 to 120 minutes postinjection. The drug also decreased mechanical dynamic allodynia and static (punctate) mechanical allodynia/hyperalgesia, but not thermal allodynia and hyperalgesia. The effects of lidocaine and mexiletine on spontaneous pain intensity were significantly higher in patients with concomitant mechanical allodynia in comparison with those without allodynia.
                These data indicate modality-specific antihyperalgesic effects of IV lidocaine in patients with peripheral nerve injury. Patients with mechanical allodynia may be good candidates for treatment with local anesthetic-like drugs and possibly with other sodium-channel blockers. Prospective randomized study to compare the efficacy of facet joint injection with lidocaine and facet joint injection with saline in two groups of patients with low back pain, with and without clinical criteria that were determined in a previous study to implicate the facet joint as the primary source of the pain.
                To assess the efficacy of single facet joint anesthesia versus placebo (saline injections) and to determine clinical criteria that are predictive of significant relief of LBP after injection.
                There is no syndrome that discriminates between lower back pain caused by facet joint and that caused by other structures. Single or double facet joint anesthesia, and single photon emission computed tomography are expensive and time-consuming procedures for selecting patients in controlled clinical trials with large populations.
                Results of a previous study showed that seven clinical characteristics were more frequent in patients who responded to facet joint anesthesia than in those who did not. In the current study, a group of 43 patients with lower back pain who met at least five criteria were compared with 37 patients who met fewer criteria. Patients randomly received injection of either lidocaine or saline into the lower facet joints. The result was considered positive if more than 75% pain relief was determined by visual analog scale. The patient, the radiologist, and the investigator were blinded. An analysis of variance was used to seek an interaction between clinical group effect and injection effect, and logistic regression analysis to select the best set of variables that would be predictive of minimum pain relief of 75% after the injection.
                There was a significant interaction between clinical group and injection effect (P = 0.003). In patients with back pain, lidocaine provided greater lower-back pain relief than saline (P = 0.01). Lidocaine also-provided greater pain relief in the back pain group than in the nonpain group (P = 0.02). The presence of five among seven variables (age greater than 65 years and pain that was not exacerbated by coughing, not worsened by hyperextension, not worsened by forward flexion, not worsened when rising from flexion, not worsened by extension-rotation, and well-relieved by recumbency), always including the last item, distinguished 92% of patients responding to lidocaine injection and 80% of those not responding in the lidocaine group.
                A set of five clinical characteristics can be used in randomized studies to select lower back pain that will be well relieved by facet joint anesthesia. These characteristics should not, however, be considered as definite diagnostic criteria of lower back pain originating from facet joints.
Lidocaine and oral analogs were safe drugs in controlled clinical trials for neuropathic pain, were better than placebo, and were as effective as other analgesics. Future trials should enroll specific diseases and test novel lidocaine analogs with better toxicity profiles. More emphasis is necessary on outcomes measuring patient satisfaction to assess if statistically significant pain relief is clinically meaningful.