Global Pain Relief Research Articles

Evaluation of polyherbal gel for musculoskeletal injuries in industrial workers.

Industrial workers often have musculoskeletal disorders due to the nature of their work. The goal was to investigate the scientific use of polyherbal gel in relieving pain and stiffness due to musculoskeletal injuries and improving activities of daily living (ADLs) in industrial workers. A pragmatic, single-blinded, randomized control study divided 200 musculoskeletal injury patients into four parallel groups (n = 50). Groups 1 and 2 were applied polyherbal gel via phonophoresis with therapeutic ultrasound and superficial massage. Groups 3 and 4 received diclofenac diethyl-ammonium 1% gel by phonophoresis and superficial massage. The Global Pain Relief Scale, Numeric Pain Rating Scale (NPRS), and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were used to measure pain, stiffness, and ADLs. Data was analyzed using one-way analysis of variance (ANOVA) and paired t-test to compare mean±SD of four independent groups before and after gel application. The confidence interval was 95%, with p < 0.05 considered significant. The results revealed that polyherbal gel reduced pain (NPRS, WOMAC and Global pain relief scales) more efficiently (p≤0.000) when applied with phonophoresis as compared to applied with massage and standard diclofenac (p≤0.005), furthermore, polyherbal gel when applied with phonophoresis showed more efficient results. Industrial workers with musculoskeletal injuries benefited from the use of polyherbal gel for pain and inflammation relief. The polyherbal gel is natural, cost-effective, and easy to formulate.

Effect and safety profile of topical lidocaine on post-surgical neuropathic pain and quality of life: A systematic review and meta-analysis

Study objectivePost-surgical chronic pain with a neuropathic component is usually more severe and leads to worse quality of life. We conducted this systematic review to examine the evidence of topical lidocaine for post-surgical neuropathic pain. DesignSystematic review with meta-analysis. SettingPublished randomized controlled trials (RCTs) comparing topical lidocaine with placebo or no topical lidocaine for post-surgical neuropathic pain. PatientsSeven RCTs including 585 patients. InterventionsWe systematically searched databases for randomized controlled trials (RCTs) investigating the effect and safety outcomes of topical lidocaine compared with placebo or no intervention. MeasurementsWe conducted meta-analyses to evaluate the effect of topical lidocaine on pain intensity, adverse events, and quality of life. Standardized mean difference (SMD) and relative risk (RR) with 95% CIs were effect measures for continuous and dichotomous outcomes, respectively. We assessed the risk of bias of included trials and the certainty of evidence for each outcome. Main resultsOur review included 7 studies with 585 participants. There is moderate certainty evidence that topical lidocaine may increase the likelihood of global pain relief, with a relative risk (RR) of 1.98 (95% confidence interval (CI): 1.04, 3.76; I2 = 70%, P = 0.04). Low certainty evidence suggested topical lidocaine may lead to more reduction in pain intensity (SMD: −0.70; 95% confidence interval: −1.46, 0.06; I2 = 93%, P = 0.07). High certainty evidence showed that topical lidocaine did not increase the adverse event risk (RR: 1.04; 95% CI: 0.93, 1.16; I2 = 0%, P = 0.51). ConclusionsTopical lidocaine may lead to pain relief and is safe to use for patient with post-surgical pain, though its impact on quality of life is unclear. This review supports the use of topical lidocaine for patients with post-surgical pain, and reveals the evidence gap in topical lidocaine use. (Registration: PROSPERO CRD42021294100).

Serious health-related suffering in Latin America: a secondary analysis

Evidence from needs analysis can support health systems and improve morbidity and mortality rates related to life-limiting and life-threatening conditions, and is essential for the development of health care and educational plans to respond adequately to the disease burden of the population. The aim of this study was to establish the number of people with serious health-related suffering, defined as a negative impact on the functioning (eg, physical, social, or emotional) of a patient with a serious illness that cannot be mitigated without medical intervention, in 19 Spanish-speaking and Portuguese-speaking Latin American countries in 1990, 2000, 2010, and 2019. We conducted a comparative secondary analysis of data from 19 Latin American countries reported on the Global Burden of Disease mortality database from the Institution for Health Metrics and Evaluation. Our analysis is premised on data generated by the Global Palliative Care and Pain Relief Research Hub spearheaded by the University of Miami's Institute for Advanced Study of the Americas. The number of people facing serious health-related suffering in Latin America doubled from 2 194 400, in 1990, to 4 268 500, in 2019. During this period, the increase in the percentage of people facing serious health-related suffering ranged from 39% (from 28 298 to 39 398 people) in Uruguay to 172% in Costa Rica (from 10 586 to 28 865 people), Panama (from 9770 to 26 651 people), and Venezuela (from 74 082 to 201 650 people). The number of no-decedents facing serious health-related suffering grew from 50% to 59% (vs decedents) during the period observed. People aged 70 years or older were the largest group facing serious health-related suffering in every country, which conversely decreased in children (aged 0-19 years). The most prevalent cause of serious health-related suffering was non-communicable disease, accounting for 63% (1990) to 72% (2019) of palliative care needs. Cancer was the largest single disease group accounting for the most serious health-related suffering in all years studied (20% in 1990; 22% in 2000; 24% in 2010; and 26% in 2019). The burden of serious health-related suffering in Latin America is large and growing. The comparison here presented shows a change in the cause of serious health-related suffering and a shift in the age groups affected, confirming an epidemiological and demographic transition in palliative care needs. None.

The value of alleviating suffering and dignifying death in war and humanitarian crises

Despite a vast literature on humanitarian crisis response, 1 UN Refugee AgencyEmergency handbook. https://emergency.unhcr.orgDate: 2015 Date accessed: March 16, 2022 Google Scholar , 2 International Committee of the Red CrossInternational Federation of Red CrossCode of Conduct for the International Red Cross and Red Crescent Movement (the Movement) and Non-Governmental Organizations (NGOs) in Disaster Relief. https://cms.emergency.unhcr.org/documents/11982/44705/Code+of+Conduct+for+the+International+Red+Cross+and+Red+Crescent+Movement+and+Non-Governmental+Organizations+in+Disaster+Relief+%28ICRC+and+IFRC%29/d362b2d1-6cae-4067-bc78-9231603c3cb5#_ga=2.120950925.427408817.1647449503-1949508229.1647449503Date: 1994 Date accessed: March 16, 2022 Google Scholar , 3 HAP InternationalPeople in AidThe Sphere ProjectCore Humanitarian Standard on Quality and Accountability. https://cms.emergency.unhcr.org/documents/11982/44705/The+Core+Humanitarian+Standard+on+Quality+and+Accountability+%28HAP+International%2C+People+In+Aid+and+the+Sphere+Project%29/53da61c9-7686-4458-b043-0fb441798338#_ga=2.129931145.427408817.1647449503-1949508229.1647449503Date: 2014 Date accessed: March 16, 2022 Google Scholar , 4 UN General Assembly58/114. Strengthening the coordination of emergency humanitarian assistance of the United Nations. https://cms.emergency.unhcr.org/documents/11982/44705/General+Assembly+Resolution+58-114/ce5ba762-019e-477e-b3a8-0b53a5d558b9#_ga=2.125802383.427408817.1647449503-1949508229.1647449503Date: 2004 Date accessed: March 16, 2022 Google Scholar , 5 The Sphere ProjectThe Sphere handbook: humanitarian charter and minimum standards in humanitarian response. https://handbook.spherestandards.org/en/sphere/#ch001Date: 2018 Date accessed: March 16, 2022 Google Scholar palliative care, pain relief, and care for the dying and bereaved need increased and urgent attention, 5 The Sphere ProjectThe Sphere handbook: humanitarian charter and minimum standards in humanitarian response. https://handbook.spherestandards.org/en/sphere/#ch001Date: 2018 Date accessed: March 16, 2022 Google Scholar , 6 WHOIntegrating palliative care and symptom relief into the response to humanitarian emergencies and crises. https://apps.who.int/iris/handle/10665/274565Date: 2018 Date accessed: March 13, 2022 Google Scholar , 7 Waldman E Glass M A field manual for palliative care in humanitarian crises. Oxford University Press, Oxford2020 Google Scholar , 8 Nouvet E Sivaram M Bezanson K et al. Palliative care in humanitarian crisis: a review of the literature. J Int Humanitar Action. 2018; 3: 5 Google Scholar , 9 Schneider M Pautex S Chappuis F What do humanitarian emergency organizations do about palliative care? A systematic review. Med Confl Surviv. 2017; 33: 263-272 Google Scholar , 10 WHOEssential medicines in palliative care (prepared by the International Association for Hospice & Palliative Care). https://www.who.int/selection_medicines/committees/expert/19/applications/PalliativeCare_8_A_R.pdfDate: 2013 Date accessed: March 13, 2022 Google Scholar , 11 Powell RA Schwartz L Nouvet E et al. Palliative care in humanitarian crises: always something to offer. Lancet. 2017; 389: 1498-1499 Google Scholar particularly in the context of armed conflict. The Lancet Commission on the Value of Death12 Sallnow L Smith R Ahmedzai SH et al. Report of the Lancet Commission on the Value of Death: bringing death back into life. Lancet. 2022; 399: 837-884 Google Scholar challenged the medicalisation of dying and death and reaffirmed the moral injustice of the global palliative care and pain relief divide. 13 Knaul FM Farmer PE Krakauer EL et al. Alleviating the access abyss in palliative care and pain relief—an imperative of universal health coverage: the Lancet Commission report. Lancet. 2018; 391: 1391-1454 Google Scholar The devastating humanitarian crisis in Ukraine raises the vital importance of these issues. 12 Sallnow L Smith R Ahmedzai SH et al. Report of the Lancet Commission on the Value of Death: bringing death back into life. Lancet. 2022; 399: 837-884 Google Scholar , 13 Knaul FM Farmer PE Krakauer EL et al. Alleviating the access abyss in palliative care and pain relief—an imperative of universal health coverage: the Lancet Commission report. Lancet. 2018; 391: 1391-1454 Google Scholar

The Concept, Development, and Application of a Home-Based High-Definition tDCS for Bilateral Motor Cortex Modulation in Migraine and Pain.

Whereas, many debilitating chronic pain disorders are dominantly bilateral (e.g., fibromyalgia, chronic migraine), non-invasive and invasive cortical neuromodulation therapies predominantly apply unilateral stimulation. The development of excitatory stimulation targeting bilateral primary motor (M1) cortices could potentially expand its therapeutic effect to more global pain relief. However, this is hampered by increased procedural and technical complexity. For example, repetitive transcranial magnetic stimulation (rTMS) and 4 × 1/2 × 2 high-definition transcranial direct current stimulation (4 × 1/2 × 2 HD-tDCS) are largely center-based, with unilateral-target focus—bilateral excitation would require two rTMS/4 × 1 HD-tDCS systems. We developed a system that allows for focal, non-invasive, self-applied, and simultaneous bilateral excitatory M1 stimulation, supporting long-term home-based treatment with a well-tolerated wearable battery-powered device. Here, we overviewed the most employed M1 neuromodulation methods, from invasive techniques to non-invasive TMS and tDCS. The evaluation extended from non-invasive diffuse asymmetric bilateral (M1-supraorbital [SO] tDCS), non-invasive and invasive unilateral focal (4 × 1/2 × 2 HD-tDCS, rTMS, MCS), to non-invasive and invasive bilateral bipolar (M1-M1 tDCS, MCS), before outlining our proposal for a neuromodulatory system with unique features. Computational models were applied to compare brain current flow for current laboratory-based unilateral M11 and bilateral M12 HD-tDCS models with a functional home-based M11−2 HD-tDCS prototype. We concluded the study by discussing the promising concept of bilateral excitatory M1 stimulation for more global pain relief, which is also non-invasive, focal, and home-based.

Long term study on the effects of microsurgical DREZotomy for chronic pain control

The DREZotomy (Dorsal Root Entry Zone tomy) is an analgesic procedure. The analgesic effect is evaluated on 30 patients with chronic pain resulting from respectively: brachial plexus avulsion (66.6%), postherpetic pain (10%), hyperspastic states (6.6%), phantom pain (6.6%), the pain in the stump (6.6%), and spinal cord injuries (3.3%). Pain intensity was evaluated using a visual analogue scale (VAS). At last evaluation, between 12 and 60 months, after DREZotomy, 93% had a good or excellent global pain relief after surgery. According to the component types of pain, 9.6% of patients had good or excellent control of the paroxysmal pain, and 84% of the continuous pain. Kaplan–Meier prediction of lasting global pain control at 60 months of follow-up was calculated at 75.5%. Comparison of the 2 corresponding Kaplan–Meier curves at long term, namely, pain control in 82.8% for the paroxysmal component and in 51.7% for the continuous component, showed a statistically significant difference (P &lt; 0.0001). Functional effects are improved by more than 70% according to patients.

Efficacy of betamethasone valerate medicated plaster on painful chronic elbow tendinopathy: a double-blind, randomized, placebo-controlled trial.

to investigate the efficacy and safety of a medicated plaster containing betamethasone valerate (BMV) 2.25 mg in patients with chronic elbow tendinopathy. randomized, double-blind, placebo-controlled study with assignment 2:2:1:1 to BMV medicated plaster applied daily for 12 hours, daily for 24 hours or matched placebo. 62 patients aged ≥18 years with chronic lateral elbow tendinopathy were randomized. The primary efficacy variable was pain reduction (VAS) at day 28. Secondary objectives included summed pain intensity differences (SPID), overall treatment efficacy and tolerability. mean reduction in VAS pain score at day 28 was greater in both BMV medicated plaster groups, -39.35±27.69 mm for BMV12-h and -36.91±32.50 mm for BMV24-h, than with placebo, -20.20±27.32 mm. Considering the adjusted mean decreases, there was a statistically significant difference between BMV12-h and placebo (p=0.0110). Global pain relief (SPID) and overall treatment efficacy were significantly better with BMV. BMV and placebo plasters had similar local tolerability and there were few treatment-related adverse events. BMV plaster was significantly more effective than placebo at reducing pain in patients with chronic elbow tendinopathies. The BMV plaster was safe and well tolerated.

Do analgesics improve functioning in patients with chronic low back pain? An explorative triple-blinded RCT

TREATMENT of patients with chronic low back pain (CLBP) aims to reduce disability, improve functional capacity, and participation. Time contingent prescription of analgesics is a treatment modality in CLBP. The impact of analgesics on functional capacity is unknown. Aim of the study was to explore the effect of analgesics on functioning measured by functional capacity evaluation, and self-reported disability in patients with CLBP. Explorative Randomized Placebo-Controlled Clinical Trial was performed in an outpatient pain rehabilitation setting on patients waiting for rehabilitation. Included patients had low back pain lasting >3 months, visual analogue scale worst pain ≥4.0 cm, and age >18 years. Outcome measures before (T0) and after treatment (T1): functional capacity, pain intensity, Roland Morris Disability Questionnaire. T1: global perceived pain relief. Patient characteristics and psychological questionnaires were assessed. Fifty patients were included in this study and were randomly assigned to 2 weeks treatment or placebo. acetaminophen/tramadol 325 mg/37.5 mg per capsule. Dose: maximum acetaminophen 1,950 mg and tramadol 225 mg per day; treatment and placebo titrated identically. Compliance and side-effects were monitored. TREATMENT effects between groups over time were compared. One patient (treatment group) was lost to follow-up. Forty-nine patients remained in the study. TREATMENT effects in primary outcomes did not differ significantly between groups. A subgroup of 10 (42%) patients (treatment group) reported global pain relief (responders) who reduced self-reported disability (p < 0.05). Responders had significantly lower catastrophizing scores. Overall treatment effects were small and non-significant. A subgroup, however, reported improved functioning as a result of treatment. Responders had lower catastrophizing scores.

Diclofenac epolamine medicated plaster in the treatment of minor soft tissue injuries: a multicenter randomized controlled trial

Objective:To investigate the efficacy and safety of a topical plaster containing diclofenac epolamine (DHEP) 1.3% in the treatment of patients with acute minor soft tissue injuries in China.Research design and methods:This prospective, randomized, double blind, placebo-controlled study had balanced random assignment to DHEP medicated plaster and placebo plaster. A total of 384 patients, aged 18–74 years, with minor soft tissue injury occurring within 72 hours of study entry were enrolled and randomized. Plasters were applied twice daily for seven consecutive days. Outcomes were assessed in three visits over 7 days, in addition to patients’ daily self-assessment and an adverse events follow-up visit on day 21.Main outcome measures:The primary efficacy endpoint was the mean change from baseline in pain on movement on a 100 mm Visual Analogue Scale (VAS) after 7 days of treatment. Secondary efficacy endpoints included pain on movement day-by-day evaluation, summed pain intensity difference, overall treatment efficacy, rescue medication consumption, and treatment tolerability.Results:Reduction in pain on movement after 7 days of treatment, the primary efficacy endpoint, was statistically significantly greater in the DHEP plaster group than with placebo (reduction in VAS pain scores −53.78 ± 16.96 vs −37.02 ± 18.30 for DHEP vs placebo, p < 0.0001). The greater analgesic effect of DHEP plaster was evident by day 1 and increased progressively throughout the treatment period. Global pain relief and overall treatment efficacy were significantly better with DHEP. Both DHEP and placebo plaster were well tolerated with few adverse events, mostly application site reactions.Conclusions:A medicated plaster containing DHEP applied to the affected site in Chinese patients with minor soft tissue injury, such as sprains, strains and contusions, was significantly more effective than placebo at reducing pain scores. Onset of action was rapid and the DHEP plaster was safe and well tolerated. The main limitation was the use of a subjective, though validated, self-reported VAS to assess the primary endpoint.

Effects of Low-Dose IV Ketamine on Peripheral and Central Pain from Major Limb Injuries Sustained in Combat

Examine response patterns to low-dose intravenous (IV) ketamine continuous infusions on multiple pain outcomes, and demonstrate effectiveness, safety, and tolerability of ketamine administration on general wards. Retrospective case series of consecutive patients given low-dose IV ketamine continuous infusions. Walter Reed Army Medical Center, Washington, DC. Nineteen eligible inpatients with neuropathic pain from major limb injuries sustained in combat with inadequate pain control from multimodal analgesia. A 3-day IV infusion of ketamine at doses ≤ 120 μg/kg/h. Daily present (PPI), average (API), and worst (WPI) pain intensity (0-10), global pain relief (GPR) (1 "no relief" to 5 "complete relief"), daily assessments of adverse events, and daily opioid requirements measured during therapy. A significant reduction in PPI (P < 0.001) and improvement in GPR (P = 0.031) was noted over time. Higher baseline WPI (≥ 7; N = 4) was associated with a significant decrease in WPI (P = 0.0388), but lower baseline WPI (N = 5) was not. Significant mean percent decreases in PPI with higher baseline PPI (N = 8; P = 0.0078) and WPI with no phantom limb pain (PLP) (N = 10; P = 0.0436) were observed. Mean percent increase in overall GPR was better for those reporting GPR scores ≤ 3 (N = 13) in the first 24 hours of therapy (P = 0.0153). While not significant, mean opioid requirement (IV morphine equivalents) decreased from 129.9 mgs ± 137.3 on day 1 to 112.14 ± 86.3 24 hours after therapy. Low-dose ketamine infusions for complex combat injury pain were safe and effective, and demonstrated response patterns over time and by baseline pain score stratification and presence or absence of PLP.

Dorsal root entry zone lesioning for pain after brachial plexus avulsion: Results with special emphasis on differential effects on the paroxysmal versus the continuous components. A prospective study in a 29-patient consecutive series

Pain after brachial plexus avulsion (BPA) is generally characterized by 2 main different components: paroxysmal (electrical shooting-like) pain, and continuous (burning) pain. Dorsal root entry zone (DREZ) lesioning, namely, the microsurgical DREZotomy (MDT) used in our practice, has proved to be a worthwhile neurosurgical treatment for this indication. However, according to previous studies, the method does not seem to demonstrate as good effectiveness in patients in whom the continuous background of pain was predominant as in patients with the paroxysmal component predominating. To obtain more insight into this problem, a prospective study on an eventual differential effect of the MDT procedure on the 2 components was undertaken. The presented series included 29 consecutive patients affected with pain after BPA who underwent an operation over the 10 last years. Pain intensity was evaluated using a visual analogue scale (VAS). At last evaluation of the 26 patients followed for 12 to 122months (60months on average) after MDT, 76.9% had a good or excellent global pain relief after surgery, ie, pain control with or without additional nonopioid medications, respectively. According to the component types of pain, 84.6% of patients had good or excellent control of the paroxysmal pain, and 73.1% of the continuous pain. Kaplan–Meier prediction of lasting global pain control at 120months of follow-up was calculated at 41.1%. Comparison of the 2 corresponding Kaplan–Meier curves at long term, namely, pain control in 76.2% for the paroxysmal component and in 43.1% for the continuous component, showed a statistically significant difference (P=.038). Hypotheses for this relative differential effect are discussed.Dorsal root entry zone lesioning is a valuable treatment for pain after brachial plexus avulsion, and is more effective in the paroxysmal component than the continuous component of the pain.

Effectiveness and Safety of Diclofenac Epolamine Topical Patch 1.3% for the Treatment of Acute Pain Due to Back Strain: An Open-Label, Uncontrolled Study

The diclofenac epolamine topical patch 1.3% (DETP) is indicated for topical treatment of acute pain due to minor strains, sprains, and contusions. This exploratory, multicenter, open-label study evaluated effectiveness and safety of DETP in patients with acute pain due to back strain. Patients aged ≥ 18 years with acute pain due to nonradicular back strain with an average pain intensity of ≥ 4 (0 = no pain, 10 = pain as bad as you can imagine) entered a 3-day observation/washout period and completed daily diary modified Brief Pain Inventory assessments. At baseline, patients with an average pain intensity of ≥ 4 started DETP treatment (q12h). Patients were treated for 7 or 14 days, depending on investigator and patient assessment of pain resolution. Primary endpoint was mean change from baseline to end of treatment in average pain intensity. Key secondary endpoints included changes from baseline in least, worst, and current pain scores and Beck Depression Inventory(®) II scores. Patients and investigators assessed patch satisfaction and global pain relief. In 123 enrolled patients, baseline mean ± standard deviation average pain score was 6.5 ± 1.3, which decreased to 2.5 ± 2.4 (P < 0.0001) at end of treatment. Similarly, least, worst, and current pain scores were also reduced (P < 0.0001). Sixty-three percent of patients achieved ≥ 50% pain reduction from baseline. At the end of treatment, most patients (88%) were satisfied or very satisfied with DETP. For 85% of patients, investigators also reported being satisfied or very satisfied with DETP. Most patients (87%) and investigators (88%, rating the patient's response) rated global pain relief as moderate to complete. Fifteen patients experienced a total of 19 adverse events (AEs), 17 of which were mild to moderate, and 2 of which were severe. Three AEs were treatment related (application site rash, nausea, and tachycardia); 1 patient had a serious AE (noncardiac chest pain) considered unrelated to DETP. In this exploratory study, patients experienced well-tolerated relief for acute pain due to back strain, with ≥ 85% of patients and their investigators expressing satisfaction with DETP treatment.

Effectiveness and Safety of Diclofenac Epolamine Topical Patch 1.3% for the Treatment of Acute Pain Due to Back Strain: An Open-Label, Uncontrolled Study

Background: The diclofenac epolamine topical patch 1.3% (DETP) is indicated for topical treatment of acute pain due to minor strains, sprains, and contusions. This exploratory, multicenter, open-label study evaluated effectiveness and safety of DETP in patients with acute pain due to back strain. Methods: Patients aged ≥ 18 years with acute pain due to nonradicular back strain with an average pain intensity of ≥ 4(0 = no pain, 10 = pain as bad as you can imagine) entered a 3-day observation/washout period and completed daily diary modified Brief Pain Inventory assessments. At baseline, patients with an average pain intensity of ≥ 4 started DETP treatment (q12h). Patients were treated for 7 or 14 days, depending on investigator and patient assessment of pain resolution. Primary endpoint was mean change from baseline to end of treatment in average pain intensity. Key secondary endpoints included changes from baseline in least, worst, and current pain scores and Beck Depression Inventory® II scores. Patients and investigators assessed patch satisfaction and global pain relief. Results: In 123 enrolled patients, baseline mean ± standard deviation average pain score was 6.5 ± 1.3, which decreased to 2.5 ± 2.4 (P < 0.0001) at end of treatment. Similarly, least, worst, and current pain scores were also reduced (P < 0.0001). Sixty-three percent of patients achieved ≥ 50% pain reduction from baseline. At the end of treatment, most patients (88%) were satisfied or very satisfied with DETP. For 85% of patients, investigators also reported being satisfied or very satisfied with DETP. Most patients (87%) and investigators (88%, rating the patient's response) rated global pain relief as moderate to complete. Fifteen patients experienced a total of 19 adverse events (AEs), 17 of which were mild to moderate, and 2 of which were severe. Three AEs were treatment related (application site rash, nausea, and tachycardia); 1 patient had a serious AE (noncardiac chest pain) considered unrelated to DETP. Conclusion: In this exploratory study, patients experienced well-tolerated relief for acute pain due to back strain, with ≥ 85% of patients and their investigators expressing satisfaction with DETP treatment.

Statistical Reanalysis of a Randomized Trial of Acupuncture for Pain Reveals Positive Effects As Well As Adverse Treatment Interactions on Pain, Attrition, and Mortality

The aim of this study was to determine, using analysis of covariance, whether a statistical reanalysis of a previously published study on neuropathic pain would reveal undetected significant effects of acupuncture and amitriptyline on pain, attrition, and mortality in HIV-infected patients. Shlay et al published an article in the Journal of the American Medical Association (1988) reporting that neither acupuncture nor amitriptyline had effects on pain in HIV-infected patients. However, they failed to perform a factorial analysis of variance (ANOVA) or covariance (ANCOVA) reflective of their core research design. Instead, research design problems necessitated the use of a relatively insensitive statistic. The originally planned study employed a completely crossed 2 x 2 design involving acupuncture and amitriptyline and their controls. Reanalyses performed on the raw data involved ANCOVA and Pearson chi-square tests. The factorial option consisted of 125 HIV-infected men with peripheral neuropathic pain, being treated at health clinics in 10 different cities. Outcome measures were pain intensity, global pain relief, attrition, and mortality. In contrast to the originally reported findings, the interactions of amitriptyline and acupuncture over time on pain intensity and pain relief were statistically significant. There were also significant effects for acupuncture and amitriptyline on attrition and mortality, particularly when baseline health was poor. Acupuncture by itself was associated with greater pain relief, whereas the combination of acupuncture and amitriptyline was associated with a reduced level of pain relief. Acupuncture without amitriptyline was associated with substantially reduced attrition and, importantly, decreased mortality. Effects involving acupuncture tended to be magnified in patients in poor health. The combination of acupuncture and amitriptyline resulted in an adverse treatment interaction on mortality, especially in patients in poor health (53% death rate for the combination of acupuncture and amitriptyline vs 11% death rate for acupuncture only). Trials of acupuncture and other treatments should use efficient statistical techniques to assure detection of significant effects. Interactions involving various combinations of acupuncture and amitriptyline, which were undetectable in the original analytical approach, revealed previously undetected beneficial, as well as adverse, effects.

Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain

Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15–90 mg), nortriptyline (25–100 mg), their combination, and a benztropine “active placebo” (0.25–1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0–10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI = [−2%, 30%]), 7% for morphine (95% CI = [−8%, 22%]), and 7% for the combination treatment (95% CI = [−4%, 18%]). Mean doses were: nortriptyline alone, 84 ± 24.44 (SD) mg/day; morphine alone, 62 ± 29 mg/day; and combination, morphine, 49 ± 27 mg/day plus nortriptyline, 55 mg ± 33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.

Topiramate in Chronic Lumbar Radicular Pain

Chronic lumbar radicular pain is the most common neuropathic pain syndrome. This was a double-blind, randomized, 2-period crossover trial of topiramate (50 to 400 mg) and diphenhydramine (6.25 to 50 mg) as active placebo to assess the efficacy of topiramate. Each period consisted of a 4-week escalation, a 2-week maintenance at the highest tolerated dose, and a 2-week taper. Main outcome was the mean daily leg pain score on a 0 to 10 scale during the maintenance period. Global pain relief was assessed on a 6-level category scale. In the 29 of 42 patients who completed the study, topiramate reduced leg pain by a mean of 19% ( P = .065). Global pain relief scores were significantly better on topiramate ( P < .005). Mean doses were topiramate 200 mg and diphenhydramine 40 mg. We concluded that topiramate treatment might reduce chronic sciatica in some patients but causes frequent side effects and dropouts. We would not recommend topiramate unless studies of alternative regimens showed a better therapeutic ratio. Perspective The anticonvulsant topiramate might reduce chronic lumbar nerve root pain through effects such as blockade of voltage-gated sodium channels and AMPA/kainite glutamate receptors, modulation of voltage-gated calcium channels, and gamma-aminobutyric acid agonist-like effects.

A Randomized Controlled Trial of 5% Lidocaine Gel for HIV-Associated Distal Symmetric Polyneuropathy

To investigate the analgesic efficacy and safety of 5% lidocaine gel in painful HIV-associated distal sensory polyneuropathy (DSP). Painful DSP, the most common neurologic complication in HIV infection, is difficult to treat. Lidocaine 5% gel was effective in alleviating neuropathic pain in an open-label study of HIV DSP. In a double-blind, placebo-controlled, crossover, multi-center study, 64 subjects were randomized to receive 5% lidocaine or vehicle gel for 2 weeks (phase A). A washout period of 2 weeks was followed by a crossover to the alternate agent for another 2 weeks (phase B). The primary outcome was difference in average pain scores (Gracely pain scale) between the 2 groups during the second week of each treatment period. Secondary outcomes included differential effect of the first treatment, difference in global pain relief, and pain response by neurotoxin exposure. The baseline pain scores of the 2 groups were similar. The average pain scores during the second week of each phase of the lidocaine gel group did not differ from those of the placebo group (phase A: lidocaine 1.09, placebo 1.15; phase B: lidocaine 1.16, placebo 1.10). There also was no difference noted in secondary outcomes. The pain responses of lidocaine gel-treated subjects with current exposure to neurotoxic antiretrovirals (1.18) did not differ compared with those without (1.10) (P = 0.358). There were no significant adverse effects. Lidocaine 5% gel is a safe but ineffective agent in the treatment of pain in HIV-associated DSP.

The effect of vagus nerve stimulation on migraines

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might reduce pain in patients with VNS device implanted for intractable seizures. One case report described possible benefits on migraines. We contacted all patients who received VNS therapy for intractable epilepsy between 1993 and 1999 at Southern Illinois University, Springfield, Illinois. Patients who had concomitant chronic pain were subsequently interviewed. Pain intensity before and after VNS implantation was rated by the patient as average, worst, and least and on numeric rating scale from 1 to 10. Current pain measurements were compared to preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who received VNS, 27 patients were interviewed; 4 patients had common migraine, and no other chronic pain syndromes were identified. All patients with migraine reported reductions in headache frequency and numeric rating scale score for average and least headache intensity. One patient reported complete relief of headaches. Improvement was reported to start 1 to 3 months after initiation of therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain relief, 2 reported a lot of pain relief, and 1 reported slight pain relief. Concomitant antiepileptic drugs were decreased in 3 patients and slightly increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

Outcome of intrathecal opioids in chronic non-cancer pain

Eighty-eight patients (58 women and 30 men; mean age 53.4 years) with chronic non-cancer pain present on average for 9.8 years were evaluated following treatment with intrathecal opioids for an average duration of 36.2 months. Outcome measures were global pain relief, physical activity levels, medication consumption, work status, intrathecal opioid side-effects, proportion of patients who ceased therapy and patient satisfaction. The most common diagnosis in this group was lumbar spinal or radicular pain after failed spinal surgery (n= 55, 63%). At the time of follow-up, mean pain relief was 60% with 74% of patients (36 of 49) reporting increased activity levels. Oral medication intake was significantly reduced (Medication Quantification Scale Score prior to implantation 31.0±2.6 and at follow-up 12.7±1.4;n= 48;p< 0.0001). These gains were not accompanied by a change in work status (43 of 50 working age patients not working at follow-up). There were frequent reports of opioid side-effects, including sexual dysfunction and menstrual disturbance. Technical complications occurred with the drug administration device, most often catheter related, requiring at least one further surgical procedure in 32 patients (40%). Patient satisfaction with intrathecal opioids was high, with 45 of 51 (88%) reporting satisfaction. Mean intrathecal morphine dose increased from 9.95±1.49mg/day (mean±SEM) at 6 months to 15.26±2.52mg/day 36 months after initiation of therapy. Drug administration systems were permanently removed in five patients (6%). Intrathecal opioid therapy appears to have a place in the management of chronic non-cancer pain. Therapy does not seem to be significantly inhibited by the development of tolerance.

Postoperative Analgesia at Home After Ambulatory Hand Surgery: A Controlled Comparison of Tramadol, Metamizol, and Paracetamol

We compared in a prospective, randomized, double-blinded study the analgesic efficacy of three drugs in 120 ASA I and II patients scheduled to undergo ambulatory hand surgery with IV regional anesthesia. At discharge, oral analgesic tablets were prescribed as follows: tramadol 100 mg every 6 h, metamizol 1 g every 6 h, and paracetamol (acetaminophen) 1 g every 6 h. Rescue medication consisted of oral dextropropoxyphene 100 mg on demand. Analgesic efficacy was evaluated by self-assessment of pain intensity by visual analog score at six different time intervals during the 48-h study period. Patients also recorded global pain relief on a 5-grade scale, total number of study and rescue analgesic tablets, frequency and severity of adverse effects, sleep pattern, and overall satisfaction. None of the study drugs alone provided effective analgesia in all patients. The percentage of patients who required supplementary analgesics was 23% with tramadol, 31% with metamizol, and 42% with acetaminophen. Tramadol was the most effective analgesic, as evidenced by low pain scores, least rescue medication, and fewest number of patients with sleep disturbance. However, the incidence of side effects was also increased with tramadol. Seven patients (17.5%) withdrew from the study because of the severity of nausea and dizziness associated with the use of tramadol. Metamizol and acetaminophen provided good analgesia in about 70% and 60% of patients, respectively, with a decreased incidence of side effects. Despite receiving oral analgesic medication, up to 40% of patients undergoing hand surgery experienced inadequate analgesia in this controlled trial. Although tramadol was more effective, its use was associated with the highest frequency and intensity of adverse effects and the most patient dissatisfaction. Metamizol and acetaminophen provided good analgesia with a small incidence of side effects. For patients undergoing ambulatory hand surgery, postoperative pain can last longer than 2–3 days, and there is a need for both better education before the procedure and oral analgesic therapy at home. Implications Despite pain medication, up to 40% of patients experienced pain at home after ambulatory hand surgery. Of the three analgesic drugs evaluated in this double-blinded study, tramadol was the most effective but was also associated with most patient dissatisfaction because of an increased incidence of nausea and dizziness. Metamizol provided somewhat better analgesia than acetaminophen. There is a need for better oral pain medication at home.