A double-blind, crossover trial of intravenous clodronate in metastatic bone pain.

After a baseline symptom and laboratory assessment, 24 patients with metastatic bone disease and pain were randomized to receive either a 4-hr intravenous infusion of 2-dichloromethylene bisphosphonate (Cl2MDP), 600 mg in 500 mL of normal saline, or a 4-hr placebo infusion, 500 mL of normal saline. The administration was double blind. After 1 wk, the assessment was repeated and the patients were crossed over to the alternate treatment. After 1 more wk, a final assessment and blinded choice by the patient and investigator took place. Of the 21 evaluable patients, 12 (57%) chose the Cl2MDP and 4 (19%) chose the placebo; 5 (24%) patients did not have a specific preference (p = NS). The investigator chose the Cl2MDP in 14 (67%) cases, placebo in 6 (29%) cases and was unable to discern a difference in 1 (5%) case (p less than 0.05). The patients and investigator made similar selections in 16 (76%) instances. On the visual analogue scale assessments, a significant decrease in pain scores was observed following the Cl2MDP infusion (p less than 0.01) and an increase in activity scores was also demonstrated (p less than 0.01). No significant difference in the daily oral morphine equivalent analgesic requirement was demonstrated for either arm. No difference in clinical and laboratory parameters of toxicity was evident between the placebo and Cl2MDP arms of the trial. Our preliminary findings suggest that Cl2MDP is safe, and has analgesic properties that may prove to be useful in the management of metastatic bone pain.     

Clinical Science (42)

Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome: a randomized, double blind, placebo‐controlled study. (Istituto Ortopedico Gaetano Pini, Milan, Italy) J Rheumatol 2000;27:1477–1483. This study evaluated the efficacy of intravenous (IV) clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) and assessed the urinary excretion of type 1 collagen crosslinked N‐telopeptide (NTx) before and after treatment. Thirty‐two patients with RSDS were randomized to receive either IV Clodronate 300 mg daily for 10 consecutive days or placebo. Forty days later, the placebo treated patients received the clodronate treatment. Outcome measures included as a primary endpoint the visual analog scale of pain (VAS, range 0–100); secondary endpoints were a clinical global assessment (CGA, range 0–3) and an efficacy verbal score (EVS, range 0–3). Clinical and biochemical assessments were performed before the treatment, 40 (T40), 90 (T90), and 180 (T180) days later. At T40 the 15 patients randomized to clodronate treatment showed significant decreases of VAS and CGA (P = 0.002, P = 0.001, respectively). Compared with the placebo group (17 patients), significant differences were found in all clinical variables. A further clinical improvement was observed throughout the study. Pooling the results of all 32 patients after clodronate treatment, at T180 the overall percentage decrease of VAS was 9.32 ± 15.6% with 30 patients significantly improved or asymptomatic. Significant inverse correlations between baseline NTx values and decreases of VAS were found at T90 (P = 0.03) and T180 (P = 0.01). No adverse events related to treatment occurred. Conclude that a 10‐day IV clodronate course is better than placebo and effective in the treatment of RSDS. NTx seems to be a predictive factor for clodronate efficacy. Comment by Susan Anderson, MD. This is a randomized double blind placbo controlled study to evaluate the efficacy of intravenous clodronate in patients with reflex sympathetic dystrophy syndrome (RSDS) or complex regional pain syndrome type I. It is also to assess the urinary excretion of type I collogen crosslink N‐telopeptide (NTx) before and after the treatment. Thirty‐two patients with complex regional pain syndrome type I were randomized to receive either a placebo or IV clodronate 300mg daily for 10 consecutive days. At the end of 40 days, the placebo group was then treated with the clodronate. The primary endpoint measures with the visual analog scale (VAS, range 0–100) and a secondary endpoint was the clinical global assessment (CGA, range 0–3), and an efficacy vocal score (EVS, range 0–3). In addition, the patient had clinical and biochemical assessments performed before the treatment at 40 days, at 90 days, and at 180 days later. The purpose of the study was valued at the efficacy of the IV clodronate in pain relief. The second purpose was to evaluate the possibility of using NTx as a predicting factor for evaluating complex regional pain syndrome type I or the clodranate efficacy. On day 40, 15 patients that were randomized to the clodronate treatment showed significant decreases in their VAS and CGA when compared with the placebo group with 17 patients. In addition, the patients who had originally received placebo infusions showed decreased VAS and CGA scores after 40 days of treatment with the clodronate when compared to their VAS and CGA scores after placebo. At 180 days, the patients continued to show significant improvement or were asymptomatic. Bisphosphonates have been proposed since 1988 for the treatment of CRPS type I. The most frequently used is pamidronate, which is given intravenously showing varied results. The pamidronate did not seem to be well tolerated. Alendronate is also given intravenously demonstrating good efficacy. It, however, has a high relapse rate. Clodronate was chosen for this study because it was efficacious in treatment of various painful skeletal disorders and was more tolerable and safe than the pamidronate. The length of the time of the study was chosen to be 10 consecutive days so that it followed the study with successful use of pamidronate. These results suggest that a 10‐day IV clodronate course is better than placebo and is an effective complex regional pain syndrome type I treatment that may induce prompt and long lasting improvement. This study also attempted to demonstrate NTx as a predictive factor for clodranate efficacy. While NTx has shown to be a specific and sensitive marker of bone resorption, in this study, they found a low association between high NTx values and the complex regional pain syndrome type I. This finding could weaken the relationship between NTx baseline values and the responsiveness to clodronate treatment. It should be noted, however, that there were significant immerse correlations found between the baseline NTx values and in the pain improvement measured on the percentage change of VAS at 90 days and 180 days. Therefore, while significant inverse correlations may have been determined, and the NTx may be a promising tool, it is not yet possible to determine the predictive rolls of NTx as a marker.     

Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain

Codeine is widely used in combination with acetaminophen and aspirin for the management of mild to moderate pain. However, there are few controlled clinical trials of single-entity codeine in chronic cancer pain. The purpose of this study was to evaluate the clinical efficacy and safety of controlled-release codeine given every 12 hr in patients with cancer pain. Thirty-five patients with chronic cancer pain were randomized in a double-blind crossover study to controlled-release (CR) codeine or placebo, for 7 days each. Pain intensity was assessed at 0800 hr and 2000 hr using a visual analogue scale (VAS) and a five-point categorical scale, and the use of “rescue” acetaminophen-plus-codeine (300 mg/30 mg every 4 hr as needed) was recorded. Thirty patients completed the study (17 male, 13 female; mean age, 64.4 ± 9.8 years) with a mean daily CR codeine dose of 277 ± 77 mg (range, 200–400 mg). CR codeine treatment resulted in significantly lower overall VAS pain intensity scores (22 ± 0.8 mm versus 36 ± 20 mm, P = 0.0001), categorical pain intensity scores (1.2 ± 0.8 versus 1.8 ± 0.8, P = 0.0001), and pain scores when assessed by day of treatment and by time of day. Daily “rescue” analgesic consumption was significantly lower on CR codeine, compared to placebo treatment (2.2 ± 2.3 versus 4.6 ± 2.8 tablets per day, P = 0.0001). Both patients and investigators preferred CR codeine to placebo (80% versus 3%, P = 0.0014 and 73% versus 7%, P = 0.0160, respectively). These data indicate that CR codeine, given every 12 hr results in significant reductions in pain intensity and the use of “rescue” acetaminophen-plus-codeine in patients with cancer pain. CR codeine provides the benefits of a flexible single entity codeine formulation and the convenience of 12-hr duration of action, which allows patients uninterrupted sleep and improved compliance.     

Ongoing visual analog score display improves Emergency Department pain care

The study purpose was to test two methods of pain assessment and display: ongoing (11 times over 2 h) visual analog scale (VAS) determination with data tabulation in the ED chart (Tabulation group), and similar VAS assessments with display of the information at the head of the ED bed (Graph group). A Control group had initial and 2-h VAS ascertainments charted (not graphed). Tertiary-care university-affiliated ED patients were randomized into the three groups and pain care outcomes assessed. Compared to Controls, those in the Graph group had the following findings (p < 0.05): 1) treating physicians more likely aware of initial and final VAS scores, 2) earlier analgesia, 3) likelier perception (by patients and physicians) that VAS was useful and likelier patient perception that pain care was adequate. Tabulation group results were intermediate to those of Control and Graph patients. The data support further investigation of VAS display as a means of improving ED pain assessment.     

Prospective randomized study of analgesic use for ED patients with right lower quadrant abdominal pain

Giving an analgesic to patients with right lower quadrant (RLQ) pain causes greater alteration of abdominal signs predictive of appendicitis than placebo. A randomized double-blinded controlled trial of 68 patients who received either tramadol or placebo. Absence or presence of seven abdominal signs (tenderness on light and deep palpation, tenderness in the RLQ and elsewhere, rebound, cough, and percussion tenderness) and pain (100 mm Visual Analog Scale [VAS]) at 0 and 30 minutes were recorded. The predictive value of each physical finding (PF) was measured using an 11-point PF score weighted by likelihood ratios. There was significant reduction in mean VAS of 14.2 mm (95% CI 5.6 to 22.8) in analgesic group versus 6.5 mm (95% CI 1.6 to 11.4) in placebo group. The analgesic group had less normalization of signs as measured by the PF score in all patients [32 of 154 (20.8%) versus 40 of 121 (33.1 %) (P = .031)] and in those with proven appendicitis [4 of 33 (12.1%) versus 10/22 (45.5%) (P = .014)]. Parenteral use of tramadol in emergency department patients with RLQ pain resulted in significant levels of pain reduction without concurrent normalisation of abdominal examination findings indicative of acute appendicitis.     

Motor cortex stimulation for refractory neuropathic pain: four year outcome and predictors of efficacy

Thirty-one patients with medically refractory neuropathic pain were included in a prospective evaluation of motor cortex stimulation. The long-term outcome was evaluated using five variables: (a) rate (percentage) of pain relief, (b) pain scores as assessed on VAS, (c) postoperative decrease in VAS scores, (d) reduction in analgesic drug intake, (e) a dichotomic (yes/no) response to the question whether the patient would accept, under similar circumstances, to be operated on again. Pain relief was rated as excellent (>70 % pain relief) in 10 % of cases, good (40-69 %) in 42 %, poor (10-39 %) in 35 % and negligible (0-9 %) in 13 %. Intake of analgesic drugs was decreased in 52 % of patients and unchanged in 45 % (unavailable data in 3 %), with complete withdrawal of analgesic drugs in 36 % of patients. Twenty-one patients (70 %) declared themselves favourable to re-intervention if the same beneficial outcome could be guaranteed. Neither preoperative motor status, pain characteristics, type or localisation of lesions, quantitative sensory testing, Somatosensory Evoked Potentials, nor the interval between pain and surgery were found to predict the efficacy of MCS. The level of pain relief, as evaluated in the first month following implantation was a strong predictor of long-term relief (regression analysis, R=0.744; p<0.0001). These results confirm that MCS can be a satisfactory and durable alternative to medical treatments in patients with refractory pain, and suggest that the efficacy of MCS may be predicted in the first month of therapy.     

Analgesic action of gabapentin on chronic pain in the masticatory muscles: a randomized controlled trial

Chronic masticatory myalgia (CMM) can be defined as constant pain in the masticatory muscles for more than 6 months and is influenced by the central nervous system. The antiepileptic agent gabapentin acts centrally and is used for managing different types of chronic pain conditions. The objective of this study was to evaluate the analgesic action of gabapentin on CMM. In this 12-week randomized controlled clinical trial 50 patients were randomly allocated into two study groups: 25 received gabapentin and 25 received placebo. The outcome measures utilized were pain reported on a VAS (VAS-pain), Palpation Index (PI) and impact of CMM on daily functioning reported on a VAS (VAS-function). Thirty-six patients completed the study. Gabapentin showed to be clinically and statistically superior to placebo in reducing pain reported by patients (gabapentin=51.04%; placebo=24.30%; P=0.037), masticatory muscle hyperalgesia (gabapentin=67.03%; placebo=14.37%; P=0.001) and impact of CMM on daily functioning (gabapentin=57.70%; placebo=16.92%; P=0.022). It can be concluded from this study that gabapentin is effective for the management of CMM.     

Critique of the Dornier HM3 lithotripter as a clinical algesimeter

The power and nociceptive intensity of shock waves generated by the Dornier HM3 extracorporeal shock wave lithotripter (ESWL) are voltage dependent and suited to algesimetry in a controllable voltage range of 8–30 kV. Fidelity of the HM3 as an algesimeter was tested by:

1. (1) In vitro measurements of shock pressure at voltages between 14 and 30 kV were recorded by a force transducer at the point of clinical focus.

2. (2) Unanaesthetized volunteer (n = 5) assessment and VAS pain scores of shocks in the range of 10–24 kV, yielding highly significant correlations between blinded randomized shock voltage (r = 0.88), and VAS scores (r = 0.84).

3. (3) Voltage-tolerance curves generated from 33 ASA class 1 or 2 patients undergoing ESWL treatment under epidural analgesia with 0.125% bupivacaine, fortified with a bolus epidural dose of 100 μg fentanyl if pain arose during treatment. Voltage tolerance was increased by 50% after an epidural bolus of 100 μg fentanyl (P < 0.001). The respiratory consequences of epidural fentanyl were assessed by changes of respiratory rate and rhythm recorded from capnographic tracings of expired carbon dioxide.

This study indicates that the Dornier HM3 system provides a valuable opportunity to conduct precise, quantitative measurements of induced deep truncal pain, as well as the effectiveness and respiratory cost of analgesic interventions directly applicable to the safe management of acute pain.     

Intra-articular (IA) catheter administration of postoperative analgesics. A new trial design allows evaluation of baseline pain,demonstrates large variation in need of analgesics,and finds no analgesic effect of IA ketamine compared with IA saline

All previous studies of intra-articular (IA) analgesic drugs for postarthroscopy pain have administered test-drugs at the end of the arthroscopic procedure, before any baseline pain could be assessed. Assay sensitivity has often not been documented or has been assumed to be present if a placebo control group had significant pain during the observation period. We present an improved study design employing an IA catheter for test-drug administration only in patients with moderate-to-severe baseline pain within 2h postoperatively. Using this technique we explored the incidence of moderate-to-severe pain and possible predisposing factors for pain through a close follow-up of all patients. The study incorporated an explanatory study of IA ketamine. A double-blind, double-dummy technique was used. Summed pain intensity differences 0-120 min after test medication was the primary outcome variable. Of 77 patients assessed for inclusion, only 45 had moderate or severe pain. Significantly more women (78%) than men (45%) had moderate-to-severe pain (P<0.005). Those not included continued to have no or mild pain and consumed less rescue analgesics than those who had high baseline pain. Mean baseline pain in the patient group with moderate or severe pain was 50mm on a 0-100 m visual analogue scale (VAS) (SD=15.1)(n=45). Mean VAS in the patient group with no or mild pain was 7.5mm (SD=8.7)(n=32).The new method for IA analgesic trials solves the problem with undesirable inclusion of patients with no or mild pain. We observed rapid onset and significant pain relief after IA injection of 10 ml saline with or without ketamine 10mg, but no difference between these two test medications. Intra-muscular ketamine 10mg showed significantly better early pain relief, global evaluation, and longer time to rescue analgesic, compared with IA ketamine 10mg.     

Efficacy and tolerability of diclofenac potassium sachets in acute postoperative dental pain: a placebo-controlled, randomised, comparative study vs. diclofenac potassium tablets

This double-blind, randomised, parallel-group trial compared the analgesic efficacy of single 50 mg doses of diclofenac potassium sachets and tablets with placebo in 184 patients with moderate/severe pain after third molar extraction. The primary efficacy variable was the average pain reduction from baseline during the first 2-h postdose, using a visual analogue scale (VAS). During the first 2-h postdose, sachets and tablets significantly reduced pain (p < 0.05) vs. placebo with an incremental benefit seen for sachets over tablets (p < 0.05). Onset of analgesic effect (VAS) was at 30 min for sachets and 45 min for tablets. Pain reduction vs. placebo (VAS) was maintained for 8 h for sachets and tablets (p < 0.05). VAS-findings were confirmed by pain relief and intensity verbal scale assessments. Fewer patients re-medicated vs. placebo. No safety issues were identified. This study demonstrates that both diclofenac potassium sachets and tablets offer patients suffering from acute pain conditions an effective treatment with incremental analgesic benefits seen for sachets.     

10% Lidocaine spray as a local anesthetic in blood gas sampling: A randomized,double-blind,placebo-controlled study

AimRadial artery blood gas sampling is a very common procedure undertaken in the emergency department to evaluate respiratory and metabolic parameters. This intervention causes both anxiety and pain for the patient. Therefore, the current study aimed to examine the analgesic efficacy of lidocaine spray compared to a placebo during radial artery blood gas sampling.MethodsThis study was conducted in the emergency department of a tertiary hospital with a randomized, double-blind, placebo-controlled design. A total of 144 patients were randomly divided into two groups: One group (n = 72) received 10% lidocaine spray and the other (n = 72) was the placebo group. The analgesic efficacy of the 10% lidocaine spray was compared with the placebo group using the Visual Analog Scale (VAS).ResultsIn the evaluation of the analgesic efficacy of the 10% lidocaine spray, the VAS score was 1.5 [interquartile range (IQR): 2.0] for the lidocaine group and 5 (IQR: 2.0) for the placebo group. The role of lidocaine spray in reducing pain was statistically significant compared to the placebo (p = 0.000).ConclusionIn blood gas sampling, 10% lidocaine spray has analgesic efficacy. Therefore, we recommend the use of lidocaine spray while performing arterial blood gas sampling in emergency departments.     

Oral ibandronate improves bone pain and preserves quality of life in patients with skeletal metastases due to breast cancer

The objective of this study is to assess the effect of oral ibandronate on bone pain and quality of life in women with metastatic bone disease from breast cancer. In two double-blind, placebo-controlled studies, 564 patients were randomised to receive oral ibandronate, 50mg once daily, or placebo for up to 96 weeks. Throughout the studies, we assessed bone pain (on a 5-point scale from 0=none to 4=intolerable), analgesic use (7-point scale) and quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 [EORTC QLQ-C30], 100-point scale). Oral ibandronate significantly reduced and maintained bone-pain scores below baseline throughout the 96-week study period (at endpoint, -0.1 vs +0.2, P=0.001 vs placebo). Analgesic use increased in both groups; however, the increase was significantly less in the ibandronate group (0.60 vs 0.85, P=0.019). Although quality of life deteriorated during the study, the decrease in quality of life was significantly lower with ibandronate therapy (-8.3 vs -26.8, P=0.032). Drug-related adverse events were generally minor and as expected with oral bisphosphonates. Oral ibandronate had beneficial effects on bone pain and quality of life and was well tolerated. These results suggest that this treatment is of considerable clinical value as a co-analgesic to patients with painful bone metastases.     

Clinically Important Change in the Visual Analog Scale after Adequate Pain Control

OBJECTIVES: To define the minimum clinically important difference (MCID) for the visual analog scale (VAS) of pain severity by measuring the change in VAS associated with adequate pain control. METHODS: The authors conducted a prospective, observational study. Adult emergency department (ED) patients with acute pain (<72 hours) were eligible. Patients rated their pain severity on a 100-mm VAS on presentation and at discharge. Patients were asked if they would accept any analgesic, then if they would accept a parenteral analgesic before treatment. At discharge, they were asked whether they had received adequate pain control. RESULTS: The authors enrolled 143 patients (mean age, 36 years; 54% female). The mean decrease in VAS was -30.0 mm (95% confidence interval [CI] = -36.4 to -23.6) for the 116 of 143 (81%) patients with adequate pain control at discharge vs. -5.7 (95% CI = -11.2 to -0.3) for the 27 with inadequate pain control (p < 0.001). At discharge, the mean VAS was 31.3 mm for those with adequate pain control vs. 55.1 for those without. Mean VAS for the 114 of 143 patients who would accept any analgesics initially was 64.7 vs. 47.1 for the 29 reporting no analgesic need. Initially, 77 patients would accept parenteral analgesics (mean VAS = 72.5 mm). CONCLUSIONS: A mean reduction in VAS of 30.0 mm represents a clinically important difference in pain severity that corresponds to patients' perception of adequate pain control. Defining MCID based on adequate analgesic control rather than minimal detectable change may be more appropriate for future analgesic trials, when effective treatments for acute pain exist.     

Pain during bone marrow aspiration: prevalence and prevention

The prevalence, intensity, determinants and prevention of pain during bone marrow aspiration (BMA) in adults are not well defined. In the first part of this prospective study (observational phase), 132 adult hematological patients undergoing BMA after local anesthesia scored the procedural pain by means of a visual analogue scale (VAS). Moderate to severe pain was defined as a VAS score exceeding 30 mm. Eighty-six percent reported procedural pain. The VAS score (mean+/-SEM) was 27.2+/-2.1 mm. Thirty-six percent of patients graded the pain as moderate to severe. In a linear regression analysis, VAS score correlated positively with the duration of the procedure (P=0.029) and negatively with the age of the patient (P=0.006). In the second part of the study (interventional phase), 100 patients were randomized to 50 mg tramadol or placebo, given orally at least one hour before BMA. VAS scores during aspiration were significantly lower in tramadol recipients versus placebo recipients (16.5+/-3.0 mm and 28.8+/-3.4 mm, respectively, P=0.003). Pretreatment with tramadol reduced the percentage of patients with at least moderate pain from 40% to 20% (P=0.029). Four tramadol and 3 placebo recipients reported side effects (dizziness or sedation). In conclusion, notwithstanding local anesthesia, the great majority of adult hematological patients experience transient pain during BMA that is of at least moderate intensity in over a third. Pretreatment with tramadol lowers pain intensity significantly and is well tolerated.     

A Trial of Intravenous Lidocaine on the Pain and Allodynia of Postherpetic Neuralgia

This study investigated the effect of intravenous lidocaine at two doses (1 mg/kg and 5 mg/kg over 2 hours) and an intravenous saline placebo on the pain and allodynia of postherpetic neuralgia (PHN). Twenty-four patients were studied using a randomized, double-blind, within-patient crossover design. Each patient received normal saline, lidocaine 0.5 mg/kg/h, and lidocaine 2.5 mg/kg/h for a 2-h period. The McGill Pain Questionnaire Short Form, visual analogue scores (VAS), and area of allodynia were measured at intervals during the infusions. Free plasma lidocaine levels were also measured. The results were statistically analyzed using Student’s t-test for paired data. The VAS for ongoing pain showed a significant reduction after all the infusions (P < 0.05). For dynamic pressure-provoked pain, the VAS was unaffected by placebo but showed a reduction at an equal level of significance with both lidocaine infusions (P < 0.05). The area of allodynia of PHN, as mapped by brush stroke, declined in association with intravenous lidocaine (0.5 mg/kg/h = P < 0.05; 2.5 mg/kg/h = P < 0.001). Placebo had no significant effect on the area of allodynia. These findings demonstrate a positive effect on pain and allodynia following a brief intravenous infusion of lidocaine. The higher dose infusion may produce plasma levels in the toxic range, with no significant clinical increase in response.     

Treatment of reflex sympathetic dystrophy (CRPS type 1): a research synthesis of 21 randomized clinical trials

A blinded meta analysis was performed on randomized clinical trials (RCT) on the medicinal treatment of reflex sympathetic dystrophy (complex regional pain syndrome type I) to assess the methodological quality and quantify the analgesic effect of treatments by calculating individual and summary effect sizes. The internal validity of 21 RCTs was investigated and the quality weighted summary effect size was calculated using a fixed effect model (Glass Δ). The methodological quality ranged from moderate to good (average 46%). Differences were found between the trials in inclusion/exclusion criteria, treatment methods, duration of treatments and trials, and measurement instruments. Statistical analysis was possible for four subgroups; one evaluating the analgesic effects of sympathetic suppressors in general (n = 12), one subgroup concerning the analgesic effects of guanethidine (n = 6), one investigating the analgesic effect of intravenous regional sympathetic blocks (n = 9), and one subgroup (n = 5) evaluating the analgesic effect of calcitonin. Except for the calcitonin subgroup (P = 0.002), the quality-weighted summary effect size of these subgroups were not significant. No significant analgesic effect by sympathetic suppressing agents could be established. Calcitonin seems to provide effective pain relief in reflex sympathetic dystrophy patients. The results of the present study show that weighting methodological quality influences the magnitude of the effect sizes of specific treatment methods. Future studies should control for methodological quality.     

Intravenous adenosine alleviates neuropathic pain: a double blind placebo controlled crossover trial using an enriched enrolment design

Adenosine analogs produce analgesic actions in nociceptive paradigms and alleviate manifestations of neuropathic pain in nerve injury models in rodents. In humans, previous work indicates an analgesic effect for adenosine administered intravenously in postoperative and neuropathic pain. In this double blind placebo controlled crossover trial, we used an enriched enrolment design to determine the effects of intravenous adenosine (50 microg/kg/min over 60min) on neuropathic pain. In Phase 1 of the trial, adenosine was administered in an open label manner, while in Phase 2 adenosine was administered in a double blind placebo controlled manner to 23 adenosine responders who had experienced a 30% or greater response in the open trial. Outcome measures included the McGill pain questionnaire (MPQ), which generates a pain rating index (PRI), and contains a visual analog scale (VAS) of pain intensity, the neuropathy pain scale (NPS), and a VAS for pain relief. Subjects also graded the degree of allodynia and hyperalgesia using a VAS. Adenosine led to a significant reduction in spontaneous pain according to the MPQ-PRI, the MPQ-VAS and the VAS for pain relief. The NPS showed a pattern similar to the MPQ-PRI, with statistically significant reductions in scales 1 (intensity), 3 (hot), 6 (sensitive), 7 (itchy) and 9 (unpleasant). Adenosine also led to a significant reduction in pinprick hyperalgesia, but not in allodynia. Three patients from Phase 1 of the trial experienced long term resolution of their pain following intravenous adenosine (5,16,25 months). The results of this study support previous reports that indicate intravenous adenosine alleviates neuropathic pain and hyperalgesia.     

The effect of prophylactic topical steroid cream on the incidence and severity of cutaneous burns following external DC cardioversion

INTRODUCTION: Cutaneous burns are a common cause of morbidity following direct current (DC) cardioversion. We designed a prospective double-blinded controlled study to determine whether the application of steroid cream prior to cardioversion reduces their incidence and severity. MATERIALS AND METHODS: Two hours before elective DC cardioversion, we applied betamethasone 0.1% cream or placebo cream over sternal and apical pad sites in 56 patients, with patients acting as their own controls. Two hours after cardioversion, a separate blinded observer measured the visual analogue pain score (VAS), sensory and pain detection thresholds, skin temperature and erythema index at sternal and apical pad sites. RESULTS: The study had an 80% power to detect a 50% difference in VAS at 2 h, accepting an alpha error of 0.05. There was no difference between pain at 2 or 24 h, skin temperature, erythema index, sensory and pain detection thresholds at pad sites treated with steroid cream or control. CONCLUSION: Topical betamethasone 0.1% cream applied 2 h before elective DC cardioversion is no more effective than placebo at reducing the pain and inflammation from cardioversion burns.     

Schmerztherapie mit Akupunktur bei Gonarthrose

The analgesic effect of acupuncture in chronic gonarthrosis pain was studied in a placebocontrolled trial completed by 97 patients. Each patient was treated twice a week, receiving 10 acupuncture treatments in all. Before and after tee course of treatment all patients were examined by an unbiased independent examiner and the overall pain score was measured over 10 days using VAS scales; functional parameters (resilience) were measured with a modified Lysholm questionnaire. Patients in the verum group (n=71) were treated according to generally accepted acupuncture treatment recommendations. Patients in the placebo group (n=26) were treated with sham acupuncture at non-acupuncture points on the homolateral leg. A follow-up examination was carried out after 3 months. After ten treatments the overall reduction in pain score was 47.5% in the verum group (follow-up 48.2%), and 26.1% in the placebo group (follow-up 26.1%). The results are statistically significant (P<0.05); they show that in gonarthrosis pain the analgesic effect of verum acupuncture exceeds that of placebo acupuncture. Measurement of the functional parameters according to the Lysholm score showed no significant change.     

Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain

The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine, 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single- and repeated-dose administration. The study was a double-blind randomized cross-over investigation in 26 coxarthrosis patients with persistent pain. After a washout period of at least 2 days with paracetamol available as rescue analgesic, each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100-mm visual analogue scale (VAS) for 8 h after the 1st and the 6th dose. The pretreatment VAS score was 31–37 mm. After the 1st dose the 8-h mean pain intensity values were 25, 27, and 26 mm after ibuprofen plus codeine, ibuprofen, and placebo, respectively. Following another 5 doses every 4 h the corresponding values were 10, 17 and 29 mm. Repeated administration of both active drugs reduced the pain intensity significantly. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. In conclusion, analgesic efficacy was better differentiated after repeated-dose than after single-dose administration. The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients.