Maximum Pain Relief Research Articles

Optimising Therapy for Patients with Neuropathic Pain

ABSTRACTNeuropathic pain is a common condition that affects people of all ages, but is especially prevalent among older people because the incidence of many diseases that cause neuropathic pain increases with age. Neuropathic pain is often underdiagnosed or undertreated, and is associated with a diminished quality of life, significant disability and depression. The principal aim of management is to improve the patient's quality of life by attaining maximum pain relief with minimal treatment‐associated adverse effects, and restoring functional ability. The current therapeutic options for the management of neuropathic pain are reviewed here, focusing on the importance of an accurate diagnosis and assessment, early intervention, regular clinical reviews and steps in pharmacological treatment.

A comparison of the analgesic efficacy of transforaminal methylprednisolone alone and with low doses of clonidine in lumbo-sacral radiculopathy

Background:Although transforaminal epidural steroid injections under fluoroscopic guidance have become a common mode of treatment of lumbosacral radiculopathy due to herniated disc, the efficacy of steroid with low doses of clonidine has not been compared yet.Objectives:Comparison of the analgesic efficacy of methylprednisolone alone and with low doses of clonidine for transforaminal injection in lumbosacral radiculopathy.Study Design:A randomized, double-blind trial.Setting:This study was performed at the Pain Clinic under the Department of Anaesthesiology, Jawaharlal Nehru Medical College Hospital, Aligarh Muslim University, Aligarh, India.Methods:One hundred and eighty ASA grade I and II patients aged between 18 and 55 years were allocated into groups I, II and III to receive methylprednisolone 60 mg alone or methylprednisolone 60 mg with or without low doses of clonidine (0.5 mcg/kg or 1 mcg/kg) as transforaminal epidural injection. Pain relief and patient's satisfaction were evaluated with the global pain scale. Follow-up visits were advised at 1, 2, 4, 6 and 12 weeks and then at 6 months after injection. Associated complications were recorded.Results:Maximum pain relief was observed at 2 weeks after injection in all the three groups, with no difference in complication rate among the three groups. The most common complication observed was paresthesia in the nerve distribution. Greater than 60% improvement in pain scores was seen in 40% of the patients in group I, 50% of the patients in group II and 75% of the patients in group III.Limitations:This study is limited by the lack of a placebo group.Conclusion:Adding 1 mcg/kg clonidine to 60 mg methylprednisolone in transforaminal epidural injections provided better pain relief than 60 mg methylprednisolone with 0.5 mcg/kg clonidine or 60 mg methylprednisolone alone in patients suffering from lumbosacral radiculopathy, with practically no significant side-effects.

Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth.

Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United Kingdom, this drug has shown promising results to date and we have chosen to also compare the combined drug with the single drugs using this model. In this review we investigated the optimal doses of both paracetamol and ibuprofen via comparison of both and via comparison with the novel combined drug. We have taken into account the side effect profile of the study drugs. This review will help oral surgeons to decide on which analgesic to prescribe following wisdom tooth removal. To compare the beneficial and harmful effects of paracetamol, ibuprofen and the novel combination of both in a single tablet for pain relief following the surgical removal of lower wisdom teeth, at different doses and administered postoperatively. We searched the Cochrane Oral Health Group'sTrials Register (to 20 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4); MEDLINE via OVID (1946 to 20 May 2013); EMBASE via OVID (1980 to 20 May 2013) and the metaRegister of Controlled Trials (to 20 May 2013). We checked the bibliographies of relevant clinical trials and review articles for further studies. We wrote to authors of the identified randomised controlled trials (RCTs), and searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied to the searches of the electronic databases. Only randomised controlled double-blinded clinical trials were included. Cross-over studies were included provided there was a wash out period of at least 14 days. There had to be a direct comparison in the trial of two or more of the trial drugs at any dosage. All trials used the third molar pain model. All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours postdosing and meta-analysed for comparison. The proportion of participants using rescue medication over both six and eight hours was also collated and compared. The number of patients experiencing adverse events or the total number of adverse events reported or both were analysed for comparison. Seven studies were included, they were all parallel-group studies, two studies were assessed as at low risk of bias and three at high risk of bias; two were considered to have unclear bias in their methodology. A total of 2241 participants were enrolled in these trials.Ibuprofen was found to be a superior analgesic to paracetamol at several doses with high quality evidence suggesting that ibuprofen 400 mg is superior to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. The risk ratio for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69; five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, and the risk ratio for not using rescue medication (also favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials).The combined drug showed promising results, with a risk ratio for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg and ibuprofen 400 mg) (one trial; moderate quality evidence), and risk ratio not using rescue medication 1.60 (95% CI 1.36 to 1.88) (two trials; moderate quality evidence).The information available regarding adverse events from the studies (including nausea, vomiting, headaches and dizziness) indicated that they were comparable between the treatment groups. However, we could not formally analyse the data as it was not possible to work out how many adverse events there were in total. There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The majority of this evidence (five out of six trials) compared ibuprofen 400 mg with paracetamol 1000 mg, these are the most frequently prescribed doses in clinical practice. The novel combination drug is showing encouraging results based on the outcomes from two trials when compared to the single drugs.

Single dose oral celecoxib for acute postoperative pain in adults.

This is an update of a review first published in The Cochrane Library in Issue 4, 2008, and updated in Issue 3, 2012. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier reviews. To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The most recent search was to 31 May 2013. We included randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain. Two review authors assessed studies for quality and extracted data. We converted summed pain relief (TOTPAR) or pain intensity difference (SPID) into dichotomous information, yielding the number of participants with at least 50% pain relief over four to six hours. We used this to calculate the relative benefit (RB) and number needed to treat to benefit (NNT), for one patient to achieve at least 50% of maximum pain relief with celecoxib who would not have done so with placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. Ten studies (1785 participants) met the inclusion criteria. The two new studies in this update had been identified in the earlier update, but data were not available. There remain three potentially relevant unpublished studies for which data are not available at this time.The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% of maximum pain relief over four to six hours was 4.2 (95% confidence interval (CI) 3.4 to 5.6) and 2.6 (95% CI 2.3 to 3.0) respectively. The median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 hours with celecoxib 400 mg, and 2.3 hours with placebo. The proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (95% CI 3.5 to 7.7) and 3.5 (95% CI 2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. Adverse events were generally mild to moderate in severity, and were experienced by a similar proportion of participants in the celecoxib and placebo groups. One serious adverse event that was probably related to celecoxib was reported. Single-dose oral celecoxib is an effective analgesic for postoperative pain relief. Indirect comparison suggests that the 400 mg dose has similar efficacy to ibuprofen 400 mg.

Treatment of Postherpetic Pain With Scrambler Therapy, a Patient-Specific Neurocutaneous Electrical Stimulation Device

Postherpetic neuropathy (PHN) is common, severe, and often refractory to treatment. We treated 10 patients with refractory PHN using Scrambler therapy, a neurocutaneous stimulation device that delivers "nonpain" information with surface electrodes. Scrambler therapy was given as 30-minute sessions daily for 10 days. Pain was recorded before and after treatment. Two centers. The average pain score rapidly diminished from 7.64 ± 1.46 at baseline to 0.42 ± 0.89 at 1 month, a 95% reduction, with continued relief at 2 and 3 months. Patients achieved maximum pain relief with less than 5 treatments. Scrambler therapy appears to have a promising effect on PHN, with prompt and continued relief and no side effects. Further research is warranted.

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543 participants for the comparison of ibuprofen 400 mg + paracetamol 1000 mg with placebo, and 359 participants for the comparison of ibuprofen 400 mg + paracetamol 1000 mg with ibuprofen 400 mg alone.The proportion of participants achieving at least 50% maximum pain relief over 6 hours was 69% with ibuprofen 200 mg + paracetamol 500 mg, 73% with ibuprofen 400 mg + paracetamol 1000 mg, and 7% with placebo, giving NNTs of 1.6 (1.5 to 1.8) and 1.5 (1.4 to 1.7) for the lower and higher doses respectively compared with placebo. For ibuprofen 400 mg alone the proportion was 52%, giving an NNT for ibuprofen 400 mg + paracetamol 1000 mg compared with ibuprofen alone of 5.4 (3.5 to 12).Ibuprofen + paracetamol at the 200/500 mg and 400/1000 mg doses resulted in longer times to remedication than placebo. The median time to use of rescue medication was 7.6 hours for ibuprofen 200 mg + paracetamol 500 mg, 8.3 hours with ibuprofen 400 mg + paracetamol 1000 mg, and 1.7 hours with placebo. Fewer participants needed rescue medication with ibuprofen + paracetamol combination than with placebo or ibuprofen alone. The proportion was 34% with ibuprofen 200 mg + paracetamol 500 mg, 25% with ibuprofen 400 mg + paracetamol 1000 mg, and 79% with placebo, giving NNTs to prevent use of rescue medication of 2.2 (1.8 to 2.9) and 1.8 (1.6 to 2.2) respectively compared with placebo. The proportion of participants using rescue medication with ibuprofen 400 mg was 48%, giving an NNT to prevent use for ibuprofen 400 mg + paracetamol 1000 mg compared with ibuprofen alone of 4.3 (3.0 to 7.7).The proportion of participants experiencing one or more adverse events was 30% with ibuprofen 200 mg + paracetamol 500 mg, 29% with ibuprofen 400 mg + paracetamol 1000 mg, and 48% with placebo, giving NNT values in favour of the combination treatment of 5.4 (3.6 to 10.5) and 5.1 (3.5 to 9.5) for the lower and higher doses respectively. No serious adverse events were reported in any of the included studies. Withdrawals for reasons other than lack of efficacy were fewer than 5% and balanced across treatment arms. Ibuprofen plus paracetamol combinations provided better analgesia than either drug alone (at the same dose), with a smaller chance of needing additional analgesia over about eight hours, and with a smaller chance of experiencing an adverse event.

Efficacy of OTC analgesics

For many 'over-the-counter' (OTC) analgesics, there is little information available about their relative efficacy. We have examined information available in a series of Cochrane reviews of single doses of analgesic drugs in acute pain and migraine for its relevance for analgesic products commonly available without prescription, at doses generally equivalent to two tablets. Pain following third molar extraction was used as a homogeneous acute pain model; with the outcome of at least 50% maximum pain relief over 6 h. For many OTC drugs, there was no information available. For some OTC drugs, there was at least some information available either for the marketed product itself, or from studies that used the same doses of drug or drugs. For acute pain, data from third molar extraction studies showed that several OTC products were highly efficacious, principally non-steroidal anti-inflammatory drugs (ibuprofen, naproxen, diclofenac) and combination products based on ibuprofen; aspirin and paracetamol-based products were less efficacious. Fixed-dose combinations, especially those with ibuprofen, provided high levels of analgesia. For migraine headache, the outcome used was pain initially moderate or severe becoming no worse than mild pain (no pain, mild pain) at 2 h. Single-dose ibuprofen 400 mg was better than aspirin and paracetamol.

Clinically relevant pain relief with an ibuprofen‐releasing foam dressing: Results from a randomized, controlled, double‐blind clinical trial in exuding, painful venous leg ulcers

The objective of this 6-week, 120-patient, double-blind, randomized, controlled trial was to investigate if a foam dressing with ibuprofen provided clinically relevant pain relief (PAR) for exuding, painful venous leg ulcers in comparison with a similar foam dressing without ibuprofen. Primary outcome parameter was PAR compared with baseline pain during the first 5 days of the investigation. PAR was registered by the patient morning and evening. Main end point was proportion of patients reporting a summed PAR score of at least 50% of the total maximum PAR (i.e., responders) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p = 0.0438). There were 34% responders in the ibuprofen foam group vs. 19% in the comparator group (NNT = 6.8). When evening data were analyzed separately to evaluate PAR over daytime, NNT was 5.3. Wound healing parameters and adverse events were comparable. In conclusion, in this study, the ibuprofen foam dressing provided clinically relevant PAR for patients with exuding, painful venous ulcers.

Once-daily gastroretentive gabapentin for the management of postherpetic neuralgia: an update for clinicians

Gabapentin was originally developed as an add-on anticonvulsant drug, but has been widely used in the USA for the management of postherpetic neuralgia since its approval for this indication in 2002. Gabapentin has a short elimination half life and limited absorption due to a saturable L-amino acid transport system, which is expressed predominantly in the proximal small intestine. Hence, the original immediate-release gabapentin formulation (gabapentin TID) must usually be taken three times a day for optimal efficacy. Gabapentin TID is also associated with a high incidence of dizziness and somnolence and some patients are unable to tolerate the doses required for maximum pain relief. A once-daily, gastroretentive formulation of gabapentin was recently approved by the US Food and Drug Administration (FDA) for the management of postherpetic neuralgia. This formulation provides gradual release of gabapentin to the optimal site of absorption in the proximal small intestine and reduces the chance of saturating intestinal uptake, thus enabling once-daily dosing of gabapentin. This gradual release and absorption have been demonstrated in pharmacokinetic studies in healthy subjects. The efficacy of once-daily gastroretentive gabapentin for the management of postherpetic neuralgia has been demonstrated in placebo-controlled clinical studies. In addition, data from these studies suggest that the incidence of dizziness and somnolence may be reduced compared with similar studies using gabapentin TID. This article provides an overview of the pharmacokinetics, efficacy, and safety of once-daily gastroretentive gabapentin for the management of postherpetic neuralgia.

Testing the Link between Sympathetic Efferent and Sensory Afferent Fibers in Neuropathic Pain

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic α-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done inrandom order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P > 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that α-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP.

Treatment of post-herpetic pain with scrambler therapy, a patient-specific neuro-cutaneous electrical stimulation device.

e19564^ Background: Post herpetic neuropathy (PHN) is common in cancer and hematologic malignancy patients. It can be debilitating and difficulty to treat effectively. Scrambler therapy, a patient-specific neurocutaneous stimulation device, can be effective in treating chemotherapy induced neuropathy (JPSM 2010) and other neuropathic pain (JPSM 2012). Methods: We treated ten patients, 2 with cancer as their primary diagnosis, with refractory PHN Scrambler therapy at two institutions. Scrambler therapy was given as 30 minute sessions daily for 10 days. Pain was recorded before and after treatment. Results: The patient mean age was 54 ± SD 13 years, 6 men and 4 women, with a mean duration of PHN for 15.6 months (range 2.5 to 48 months) without satisfactory relief despite conventional drugs. The average pain score rapidly diminished from 7.64 ± 1.46 at baseline to 0.42 ± 0.89 at one month, a 95% reduction, with continued relief at 2 and 3 months. Patients achieved maximum pain relief with less than 5 treatments. Conclusions: Scrambler therapy appears to have a promising effect on PHN, with prompt and continued relief and no side effects. Further research is warranted. [Table: see text]

Radiofrequency Neurolysis Versus Local Nerve Infiltration in 42 Patients with Refractory Chronic Inguinal Neuralgia

Background: Chronic inguinal neuralgia involving ilioinguinal and iliohypogastric nerves is a frequent complication of surgical procedures involving a lower abdominal incision such as hernia repair, appendicitis surgery, or cesarean sections. Chronic inguinal neuralgia is a very painful condition and diagnosis can be challenging as it is an overlooked impairment. Existing specific treatments are inefficient and often fail. Objective: The purposes of this study are to describe, evaluate, and compare ilioinguinal and iliohypogastric radiofrequency neurolysis (RFN) and local injection. Study Design: Retrospective comparison cohort study from 2005 to 2011. Setting: A single center, Academic Interventional Pain Management Unit Methods: Forty-two patients suffering from chronic inguinal pain refractory to specific medication were included. A total of 18 RFN procedures (14 patients) and 28 injections (28 patients) were performed. Pain was assessed in both groups using Visual Analog Scale (VAS) scores (0-10) measured immediately before and after the procedure and at one, 3, 6, 9, and 12 months after the procedure. Mean duration of pain prior to the procedure and mean duration of pain relief were noted. Moreover, mean maximum early pain relief was assessed. All procedures were ambulatory under computed tomography (CT) guidance. Injections contained 1.5 mL of cortivazol and 3 mL of lidocaine-ropivacaine (30%-70%). Radiofrequency neurolysis was performed using a Neurotherm RF Generator. In both cases, 22-gauge needles were used. After needle retrieval, control slices were taken and the patient was supervised for 30 minutes at the CT unit. Results: The mean age in both groups was 48.7 years. Forty-two patients (97.6%) presented postsurgical inguinal pain, 62% of which occurred after hernia repair. All included patients had undergone previously unsuccessful pain therapies. Mean VAS scores were 7.72 in the RF group and 7.46 in the infiltration group. Maximum early pain relief did not statistically differ (77% in the RFN group and 81.5% in the injection group). Mean duration of pain relief was statistically significant (P = .005) in the RF group (12.5 months) compared to the infilitration group (1.6 months). Mean VAS scores during the year following the procedure were all significantly in favor of radiofrequency neurolysis management. Limitations: Those inherent to small study samples and retrospective studies. Conclusion: Radiofrequency neurolysis appears to be significantly more effective than local nerve infiltrations. It is a safe and effective treatment for chronic inguinal pain. Local steroid injection along with local injection of anesthetics should be used as a confirmation of ilioinguinal neuropathy before performing radiofrequency neurolysis. Key words: Radiofrequency, Ilioinguinal, Iliohypogastric, neuropathy, infiltration, computed tomography guidance.

Single dose oral celecoxib for acute postoperative pain in adults.

This is an update of a review published in The Cochrane Library 2008, Issue 4. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor usually prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier reviews. To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Database, and ClinicalTrials.gov. The most recent search was to 3 January 2012. We included randomised, double-blind, placebo-controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain. Two review authors assessed studies for quality and extracted data. We converted summed pain relief (TOTPAR) or pain intensity difference (SPID) into dichotomous information, yielding the number of participants with at least 50% pain relief over four to six hours, and used this to calculate the relative benefit (RB) and number needed to treat to benefit (NNT) for one patient to achieve at least 50% of maximum pain relief with celecoxib who would not have done so with placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. Eight studies (1380 participants) met the inclusion criteria. We identified five potentially relevant unpublished studies in the most recent searches, but data were not available at this time. The number of included studies therefore remains unchanged.The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% of maximum pain relief over four to six hours was 4.2 (95% confidence interval (CI) 3.4 to 5.6) and 2.5 (2.2 to 2.9) respectively. The median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 with celecoxib 400 mg, and 2.3 hours with placebo. The proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (3.5 to 7.7) and 3.5 (2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. Adverse events were generally mild to moderate in severity, and were experienced by a similar proportion of participants in celecoxib and placebo groups. One serious adverse event probably related to celecoxib was reported. Single-dose oral celecoxib is an effective analgesic for postoperative pain relief. Indirect comparison suggests that the 400 mg dose has similar efficacy to ibuprofen 400 mg.

Effective Treatment of Post-Herpetic Neuropathy With Scrambler Therapy, Patient-Specific Neurocutaneous Electrical Stimulation (311-C)

1.Recognize the incidence and severity of post-herpetic neuralgia.2.Recognize the effectiveness of patient-specific neurocutaneous electrical stimulation with Scrambler Therapy. Post-herpetic neuropathy (PHN) or post-shingles pain affects at least 7%-19% of shingles patients with increasing frequency by age. To date, no therapy has been uniformly effective in either preventing or treating PHN. Therapies such as gabapentin, tricyclic antidepressants, or pregabalin plus transcutaneous electrical nerve stimulation (TENS) reduce pain in about one-third of patients but have side effects and require ongoing treatment. Scrambler therapy has been effective for refractory chemotherapy induced peripheral neuropathy and refractory neuropathic pain. To determine the effectiveness of Scrambler Therapy on PHN. Each person was treated for 30-45 minutes as an outpatient for 10 working days. The patients in Italy were treated with Scrambler Therapy on the randomized trial, and patients in Virginia were treated on an open access trial, MCC 13098. All patients gave informed written consent and all studies were approved by the relevant ethics board. We treated 10 patients with long standing established PHN and observed a dramatic reduction in pain. The patient mean age was 54 ± SD 13 years, 6 men and 4 women, with a mean duration of PHN for 15.6 months (range, 2.5-48 months) without satisfactory relief despite conventional drugs. Average pain score rapidly diminished from 7.64 ± 1.46 at baseline to 0.42 ± 0.89 at one month, a 95% reduction, with continued relief at 2 and 3 months. Patients achieved maximum pain relief with less than 5 treatments. Most patients were able to stop or reduce their pain medicines completely. Five of 10 patients had complete disappearance of pain which has continued. As in other trials of Scrambler Therapy, no side effects were observed.

Modeling the Onset and Offset of Dental Pain Relief by Ibuprofen

Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.

Single dose oral analgesics for acute postoperative pain in adults.

Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken.There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions.NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids.Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (≥ 8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg.Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours. There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

Assessment of set-up discrepancies using daily portal imaging during radiotherapy treatment for patients with spine and bone metastases

AbstractIt is well established that patients with bone metastases get good pain relief from radiotherapy. The aim of treatment is to achieve maximum pain relief with minimum morbidity. Accuracy and reproducibility of the patient’s position are fundamental to the successful delivery of radiation therapy. It has been recognised for many years, that the accuracy of patient positioning will improve the success of radiation treatment. A previous study carried out in the department showed that the use of only a single tattoo for the set-up of palliative patients resulted in poor accuracy. The aim of this study was to assess if the addition of extra skin marks improved the set-up accuracy of palliative patients being treated for spine and bone metastases. A protocol was implemented detailing the extra skin marks to be used. Daily portal images were acquired and analysed retrospectively using anatomy matching. The results obtained were then compared with those of the previous study. The use of extra skin marks resulted in a total of 45% of images within 5 mm tolerance compared with 36% of images in patients treated with a single centre tattoo. Also, the number of images with deviations greater than 15 mm was reduced by more than 50% with the addition of extra skin marks. This study has shown that extra skin marks do increase the set-up accuracy in palliative patients treated for spine and bone metastases. Therefore, the practice of using extra skin marks has become standard protocol for all palliative patients within the department.

Analgesic efficacy of an ibuprofenreleasing foam dressing compared with local best practice for painful exuding wounds

To examine if wound aetiology has an effect on the pain-relieving properties of an ibuprofen-releasing foam dressing, which was previously shown to reduce pain in wounds of various aetiologies, compared with local best practice (LBP). This was a secondary analysis of data from a multicentre, randomised, parallel group trial of patients with painful exuding wounds of various aetiologies. Wound aetiology was determined at enrolment. Of 853 patients enrolled into the trial, 688 belonged to a wound aetiology subgroup that included >25 patients and were included in the analysis reported here. Patients were randomised to a dressing containing 112.5mg of ibuprofen (ibuprofen foam) or to LBP for 5 days. Patients recorded pain relief and pain intensity daily. The main endpoint was the proportion of patients who, from day 1 to day 5, reported a summed pain relief score >50% of the total maximum pain relief score (TOTPARD5>50%) and the corresponding number needed to treat (NNT) for each wound aetiology subgroup. Further analyses included the proportion of patients who, on a daily basis, reported pain relief >50% of the maximum daily pain relief, the proportion of patients who, on day 5, experienced a reduction in pain intensity of >50% of the maximum score (PIDD5>50%), and if PIDD5>50% was related to baseline pain intensity. Patients were categorised by the following five wound types: arterial, venous, and mixed arterial-venous leg ulcers, vasculitis and traumatic ulcers. The ibuprofen foam dressing was associated with significantly greater pain relief than LBP in all different wound aetiology subgroups, whether chronic or traumatic (acute). Overall, TOTPARD5>50% was 55% in the ibuprofen foam group and 24% in the LBP group (p<0.0001; NNT, 3.2). The pain intensity evaluations revealed similar results in favour of ibuprofen foam compared with LBP. No correlation was observed between PIDD5>50 and initial pain intensity. In this study, the ibuprofen foam dressing was shown to consistently relieve wound pain in exuding wounds of various aetiologies, irrespective of basal pain intensity. The data suggest that local pain relief by an ibuprofen foam dressing is possible in the most common, painful, exuding, chronic and acute/traumatic wounds and so is a safer alternative to systemic pain treatment.

Hypoalgesia in Response to Transcutaneous Electrical Nerve Stimulation (TENS) Depends on Stimulation Intensity

Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18–64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups ( P < .0001) at the forearm; Transient Placebo TENS and No Current Placebo TENS groups at the hand ( P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r 2 = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. Perspective This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief.

Opioid use in chronic noncancer pain: guidelines revisited

The treatment of chronic noncancer pain with opioids is controversial. This review aims to find answers to three questions patients and physicians might have: how much (pain relief can be expected), how long (will pain relief be sustained) and how bad (are side-effects)? To this end, we reviewed the second generation of clinical guidelines on this topic. These are based on a significantly higher number of randomized controlled trials than former ones and, therefore, allow evidence-based statements. Six guidelines have been launched recently to improve care and safety when treating chronic noncancer pain with opioids. The evidence base for long-term administration of opioids is weak, mostly due to methodological flaws in the available studies and because opioids have no superior effects compared with other analgesics. The maximum pain relief attributable to opioid or nonsteroidal anti-inflammatory drug administration for up to 3 months is 8-12 out of 100 units. It is doubtful that this is clinically important for patients with chronic noncancer pain. Even selected 'responders' from previous randomized controlled trials do not report noticeable pain relief. The small effect-size differences between the classes of analgesic drugs do not provide a basis for differential therapeutic decisions. Many guideline panels concentrate their recommendations solely on safety of opioid analgesics and patients are usually not informed about the (low) degree of pain relief to be expected. This makes adherence of patients unlikely. Beyond that, multimodal treatment of chronic noncancer pain should become the center of attention.