Analgesic Effects of Intravenous Lidocaine and Morphine on Postamputation Pain: A Randomized Double-blind, Active placebo-controlled, Crossover Trial

Background: Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains.

Methods: The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects' self-reported pain relief and satisfaction were assessed at the end of each infusion.

Results: Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01) when compared with placebo (9.6 +/- 21.0).     

Morphine versus Mexiletine for Treatment of Postamputation Pain: A Randomized, Placebo-controlled, Crossover Trial

Background: Stump and phantom pains are debilitating sequelae of amputations that are often resistant to treatment. The efficacy of pharmacologic therapies, including opioids and sodium channel blockers, for postamputation pain is uncertain.

Methods: The authors conducted a double-blind, randomized, placebo-controlled, crossover study in adult patients with postamputation pain of 6 months or longer and greater than 3 on a 0-10 numeric pain rating scale. Each of the three treatment periods (morphine, mexiletine, or placebo) included a 1-week drug-free interval followed by 4-week titration, 2-week maintenance, and 2-week drug-taper phases. The primary outcome measure was change in average pain intensity from the drug-free baseline to the last week of maintenance.

Results: Sixty amputees were enrolled; data were analyzed from 56 subjects for one drug period, 45 subjects for two drug periods, and 35 subjects who completed all three drug periods. The mean morphine and mexiletine dosages were 112 and 933 mg, respectively. Morphine treatment provided lower pain scores compared with placebo and mexiletine (P = 0.0003). The mean percent pain relief during treatment with placebo, mexiletine, and morphine was 19, 30, and 53%, respectively (P < 0.0001, morphine vs. placebo and mexiletine). The numbers needed to treat to obtain 50% and 33% decreases in pain intensity with morphine were 5.6 and 4.5, respectively. Treatment with morphine was associated with a higher rate of side effects.     

A Randomized Study of the Effects of Single-dose Gabapentin versus Placebo on Postoperative Pain and Morphine Consumption after Mastectomy

Background: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy.

Methods: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively.

Results: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P < 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects.     

Effects of Pulsed Electromagnetic Fields on Postoperative Pain: A Double-Blind Randomized Pilot Study in Breast Augmentation Patients

BACKGROUND: Postoperative pain may be experienced after breast augmentation surgery despite advances in surgical techniques which minimize trauma. The use of pharmacologic analgesics and narcotics may have undesirable side effects that can add to patient morbidity. This study reports the use of a portable and disposable noninvasive pulsed electromagnetic field (PEMF) device in a double-blind, randomized, placebo-controlled pilot study. This study was undertaken to determine if PEMF could provide pain control after breast augmentation. METHODS: Forty-two healthy females undergoing breast augmentation for aesthetic reasons entered the study. They were separated into three cohorts, one group (n = 14) received bilateral PEMF treatment, the second group (n = 14) received bilateral sham devices, and in the third group (n = 14) one of the breasts had an active device and the other a sham device. A total of 80 breasts were available for final analysis. Postoperative pain data were obtained using a visual analog scale (VAS) and pain recordings were obtained twice daily through postoperative day (POD) 7. Postoperative analgesic medication use was also followed. RESULTS: VAS data showed that pain had decreased in the active cohort by nearly a factor of three times that for the sham cohort by POD 3 (p < 0.001), and persisted at this level to POD 7. Patient use of postoperative pain medication correspondingly also decreased nearly three times faster in the active versus the sham cohorts by POD 3 (p < 0.001). CONCLUSION: Pulsed electromagnetic field therapy, adjunctive to standard of care, can provide pain control with a noninvasive modality and reduce morbidity due to pain medication after breast augmentation surgery.     

Pain Amelioration after Thoracotomy: A Prospective,Randomized Study

Twenty patients undergoing a posterolateral thoracotomy for lung resection or a nonpulmonary procedure were divided into four groups. Group 1 was the control group. Patients in Group 2 had an intercostal nerve block at the time of closure. Those in Group 3 underwent a continuous intercostal nerve block for five days. Electronic pain control was used in Group 4. An additional group of patients underwent operation through an anterolateral thoracotomy (Group 5) and was compared with the control group. Breathing performance was evaluated daily for five days with bedside spirometry, and intergroup comparison was done utilizing the unpaired t test and analysis of variance. Forced expiratory volume in one second, expressed as percent of preoperative values, was significantly better in Group 3 (continuous intercostal nerve block) at 52.4 ± 9.2% (standard deviation; p < 0.05) and in Group 5 (anterolateral thoracotomy) at 52.0 ± 7.5% (p < 0.05) than in the control group (38.4 ± 8.8%) five days postoperatively. It is concluded that bedside spirometry is a simple and reliable technique to assess postoperative changes in ventilatory mechanics due to pain. The pain that follows posterolateral thoracotomy can be substantially decreased with a continuous intercostal nerve block. Anterolateral thoracotomy is notably less painful than posterolateral thoracotomy and should be considered the approach of choice for patients with decreased pulmonary reserve who undergo uncomplicated pulmonary resection.     

加巴喷丁治疗神经病理性疼痛的理论与临床应用

加巴喷丁（Gabapentin，又名Neurontin）是近年来广泛应用于治疗癫痫的药物，亦是当前国外临床应用与研究的热点课题。国内对此药的认识刚刚起步，而且被定为抗癫痫类药物，实际上它是属于一种治疗神经病理性疼痛的镇痛药。国内已有文章介绍。加巴喷丁于1993年首先在英国上市用于治疗癫痫大发作，同年美国FDA批准其临床应用。此后成为世界范围广泛应用于治疗癫痫的新药；     

Gabapentin for the Treatment of Dysesthetic Pain After Reconstructive Surgery

BACKGROUND: Debilitating, postoperative dysesthetic pain after reconstructive surgery is a rare but problematic complication. Conventional therapy is either marginally effective or fraught with side effects. Gabapentin is a new, novel antiepileptic drug helpful in the management of other pain states. OBJECTIVE: A case of disturbing, postoperative dysesthetic pain after reconstructive surgery is presented. METHODS: A trial of gabapentin in escalating dose was initiated and the results and side effects were recorded. RESULTS: Treatment with gabapentin was associated with a substantial decrease in pain, which relapsed after tapering the medication. Relief was obtained with dose escalation, and a successful taper was eventually accomplished. Side effects were minimal. CONCLUSION: This is the first reported use of gabapentin in the treatment of postoperative dysesthetic pain. Although this type of neuropathic pain is difficult to manage, gabapentin produced substantial relief with few side effects. Further investigation is warranted.     

Micronized Flavonoids in Pain Control After Hemorrhoidectomy: A Prospective Randomized Controlled Study

Purpose. We conducted a prospective randomized controlled study to evaluate the effect of micronized flavonoid fractions (MFF) on pain after hemorrhoidectomy. Methods. The subjects were 112 consecutive patients randomly assigned either to receive MFF (group 1) for 1 week or not to receive MFF, as a control (group 2), after hemorrhoidectomy, The severity of pain and the number of intramuscular analgesic injections required were recorded for the first 3 days, then 1 week after hemorrhoidectomy. The number of days that intramuscular analgesic injections were required, hospital stay, and patient satisfaction were also assessed. Results. On postoperative day (POD) 1, there were no significant differences between the parameters of the two groups, but on PODs 2 and 3, both the pain score (P = 0.033 and P = 0.011, respectively) and the number of patients who required intramuscular analgesic injections were significantly less in group 1 (P = 0.022 and P = 0.007, respectively). Moreover, the hospital stay was shorter and patient satisfaction was superior in group 1 (P = 0.001 and P = 0.001, respectively). After 1 week, the pain score and number of intramuscular analgesic injections given were significantly less in group 1 (P = 0.001 and P = 0.021). Conclusion. Using MFF after hemorrhoidectomy reduced the severity of pain and intramuscular analgesic requirement.     

Intravesical Capsaicin for Treatment of Severe Bladder Pain: A Randomized Placebo Controlled Study

Purpose

Present therapeutic approaches to control bladder pain are clinically and scientifically unsatisfactory, and pain in the lower urinary tract remains a challenge even to the skilled urologist. A randomized placebo controlled study was done to evaluate intravesical capsaicin for severe bladder pain. Followup was 6 months.

Materials and Methods

A total of 36 patients was prospectively randomized into those receiving 10 micromolar intravesical capsaicin twice weekly for 1 month (group 1) or placebo (group 2). All patients had pelvic pain for at least 6 months, and had no urinary tract infection within the last 3 months, functional disorders of the lower urinary tract, or other vesical or urethral pathology. Pretreatment voiding pattern and pain score were recorded. Patients were evaluated immediately at the end of treatment (primary end point) and 6 months later (secondary end point).

Results

Both groups were adequately homogenous with regard to age, sex ratio, duration of disease, voiding pattern and pain score. At both end points group 1 had significant improvement in frequency and nocturia but no improvement in urgency. No change was noted in group 2. A significant decrease in pain score was found in group 1 at the primary (mean plus or minus standard deviation 3.22 plus/minus 0.42, p less than 0.01) and secondary (3.83 plus/minus 0.47, p less than 0.01) end points compared to before treatment (5.61 plus/minus 0.40, chi-square with 2 degrees of freedom 29.25, p less than 0.0001). A significant improvement was also observed in the placebo group, in which the pretreatment pain score (5.47 plus/minus 0.37) was decreased at the primary (4.47 plus/minus 0.36, p less than 0.01) and secondary (4.48 plus/minus 0.34, p less than 0.01, chi-square with 2 degrees of freedom 12.71, p less than 0.002) end points. There were no statistically significant differences between the 2 groups.

Conclusions

We confirmed the beneficial effect of intravesical instillation of capsaicin on voiding pattern in patients with hypersensitive disorders (frequency and nocturia). We could not confirm improvement in pain score after capsaicin treatment compared to placebo. Possibly a larger dose of capsaicin would be more effective in controlling pain and neurological disease of the bladder.     

Effects of Nicotine on Spinal Cord Injury Pain: A Randomized,Double-Blind,Placebo Controlled Crossover Trial

Background:

One factor affecting spinal cord injury (SCI)–related pain may be nicotine. Case reports have described a worsening of neuropathic pain from smoking and relief from abstinence. Neurobiological correlates also implicate the potential effect of nicotine on SCI-related pain.

Method:

The current study employed a randomized, placebo-controlled crossover design to examine the effect of nicotine exposure on subtypes of SCI-related pain among smokers and nonsmokers.

Results:

Whereas nonsmokers with SCI showed a reduction in mixed forms of pain following nicotine exposure, smokers with SCI showed a converse increase in pain with regard to both mixed and neuropathic forms of pain. The exacerbation of pain in chronic nicotine or tobacco users may not only elucidate possible pain mechanisms but may also be of use in smoking cessation counseling among those with SCI.     

Combined Preoperative Use of Celecoxib and Gabapentin in the Management of Postoperative Pain

Background  In 2005 we reported a study on the efficacy of the preoperative use of the selective COX-2 inhibitor celecoxib (Celebrex) for reducing both postoperative pain and opioid requirements in patients undergoing bilateral subpectoral breast augmentation. Our findings showed that patients who received 400 mg of celecoxib 30 min before surgery required significantly less postoperative opioid analgesics compared with those given a placebo. Gabapentin (Neurontin) is an agent commonly used to control neuropathic pain. Here we describe a prospective study assessing the efficacy of preoperative gabapentin in combination with celecoxib for reducing postoperative pain and opioid requirements in elective subpectoral breast augmentation. Methods  One hundred eighteen patients were given 1200 mg of gabapentin and 400 mg of celecoxib 30–60 min before surgery. From the day of surgery until postoperative day 5, patients documented any use of analgesics and recorded their degree of pain. Results were then compared with those of our previous study in which only celecoxib was used. Results  The combination of gabapentin and celecoxib was found to be significantly superior (p < 0.001) in reducing postoperative pain and opioid requirements than celecoxib alone in the management of postoperative pain and opioid requirements. Conclusion  To decrease postoperative opioid requirements, we recommend 400 mg of celecoxib and 1200 mg of gabapentin taken 30–60 min before surgery by patients undergoing subpectoral breast augmentation or a comparable plastic surgery procedure.     

Randomized, Prospective, Double-Blind Study of the Effects on Pain Perception of Lidocaine Jelly Versus Plain Lubricant During Outpatient Rigid Cystoscopy

Purpose

There is no clear evidence that intraurethral lidocaine jelly decreases pain and/or makes rigid cystoscopy more tolerable for patients. Since lidocaine jelly is significantly more expensive than plain lubricant, we attempted to assess the true benefit of this agent.

Materials and Methods

We performed a randomized, prospective, double-blind study to compare the anesthetic effects of intraurethral 2% lidocaine jelly versus plain lubricant in patients undergoing rigid cystoscopy. Unlike previous studies, we ensured adequate urethral filling by using 30 cc of each agent and we waited 20 minutes after instillation of the agent before performing cystoscopy to allow adequate absorption. Cystoscopy was performed using a 17 to 21F rigid instrument. A total of 189 patients was entered into the study but 10 were excluded from analysis due to incomplete questionnaires. A 10-point scale (1-least to 10-most painful) was used to measure pain perception.

Results

In men pain perception was significantly decreased when lidocaine jelly was used (mean plus or minus standard error 3.00 +/− 0.21 versus 4.36 +/− 0.37 points, p = 0.002). In women there was no observed difference in pain perception when lidocaine jelly or plain lubricant was used (3.21 +/− 0.38 versus 3.11 +/− 0.30 points, p = 0.823). Patient race, performance of a related procedure, cystoscope size or history of cystoscopy did not significantly affect reported pain scores. There was a slight decrease in pain perception with increasing age (-0.23 +/− 0.10 points per decade, p = 0.021). The level of patient anxiety before cystoscopy was also significantly associated with pain perception (p <0.001).

Conclusions

Lidocaine jelly offers no advantage over plain lubricant in regard to pain control during rigid cystoscopy in women. However, when used in adequate amounts and allowed to dwell in the urethra for 20 minutes before cystoscopy, lidocaine jelly can significantly decrease pain in men.     

Analgesic Effects of Gabapentin after Spinal Surgery

Background: A combination of opioid and nonopioid analgesic drugs may improve the quality of postoperative analgesia as well as reduce opioid requirements and their associated side effects. Studies have shown synergism between gabapentin and morphine in animal and human experiments and in the treatment of incisional pain. Therefore, the authors investigated, in a randomized, placebo-controlled, double-blind study, the effects of gabapentin on acute postoperative pain and morphine consumption in patients undergoing spinal surgery.

Methods: After standard premedication, 25 patients in the control group received oral placebo, and 25 patients in the gabapentin group received 1,200 mg of gabapentin, 1 h before surgery in a randomized fashion. Anesthesia was induced with propofol and cisatracurium and was maintained with sevoflurane and remifentanil. The total intraoperative remifentanil consumption by each patient was noted. All patients postoperatively received patient-controlled analgesia with morphine (1 mg/ml) with an incremental dose of 2 mg, a lockout interval of 10 min, and a 4-h limit of 40 mg. The incremental dose was increased to 3 mg, and the 4-h limit to 50 mg, if analgesia was inadequate after 1 h. Patients were questioned for the first 1 h in the PACU and were later evaluated in the ward at 1, 2, 4, 6, 12, and 24 h. Pain scores, heart rate, oxygen saturation measured by pulse oximetry, mean blood pressure, respiratory rate, sedation, morphine use, and total dose of morphine were recorded.

Results: Overall, pain scores at 1, 2, and 4 h were significantly lower in the gabapentin group when compared with the placebo group. Total morphine consumption in the gabapentin group was 16.3 +/- 8.9 mg (mean +/- SD) versus 42.8 +/- 10.9 mg in the placebo patients. The incidence of vomiting and urinary retention was significantly (P < 0.05) higher in the placebo group, but there was no difference in incidence of other adverse effects between the groups.