Postherpetic neuralgia (PHN) interferes with patients’ quality of life, and disturbed sleep is a prevalent complaint. Pain-associated sleep interference in turn enhances pain and/or reduces pain tolerance. Therefore, reducing sleep interference by pain, in addition to pain control, may improve patient care. To address this notion, we characterized relationships among changes in pain intensity, sleep interference, and overall impression of improvement in PHN patients treated with gastroretentive gabapentin (G-GR).n = 556) received G-GR 1800 mg once-daily in two phase 3 and one phase 4 study. Visual Analog Scale (VAS) and Brief Pain Inventory (BPI) were completed at baseline and the end of study. Patients’ Global Impression of Change (PGIC) was completed at the end of study. Regression analyses examined relationships between VAS, BPI sleep interference by pain, and PGIC.Patients with PHN , and were independent predictors of feeling “Much” or “Very Much” improved on the PGIC.At the end of treatment, 53.7 and 63.2 % of patients reported a ≥30 % reduction in VAS and BPI pain-associated sleep interference (BPISI) respectively; 46.3 % reported feeling “Much” or “Very Much” improved on the PGIC. There were positive correlations between the percent reductions in VAS and BPISI; both correlated with PGIC improvements. Percent changes in VAS and BPISI were significant (Reductions in pain intensity and in BPISI were correlated, and both also correlated with overall impression of improvement for patients with PHN treated with G-GR. Both pain relief and improvement BPISI independently predicted improvement in PGIC. For optimal patient care, clinicians should consider reducing the impact of pain on quality of sleep as well as overall pain reduction.NCT00335933, NCT00636636, NCT01426230.ClinicalTrials.gov numbers,  Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome resulting from nerve damage caused by the varicella zoster virus that is reactivated during acute herpes zoster  . PHN, whAlthough the beneficial effect of various formulations of gabapentin G-GR , 16, gab, gab16, Individual patient data from 566 PHN patients in two double-blind, randomized, placebo-controlled phase 3 studies (NCT00335933 and NCT 00636636) and one open-label, single-arm phase 4 study NCT01426230) were pooled in the analysis. Patient inclusion and exclusion criteria of individual studies included in this analysis have been described in detail elsewhere –23. Brie0 were poAll three studies shared a similar G-GR treatment schedule: a 2-week titration period, a stable dose treatment period , and a 1-week dose tapering period. The 2-week titration period used a set schedule: Day 1: 300 mg; Day 2: 600 mg; Days 3–6: 900 mg; Days 7–10: 1200 mg; Days 11–14: 1500 mg; Day 15: 1800 mg.In the current analysis, pain intensity scores were from the 100-mm VAS, which was used in all three studies. For the phase 3 studies, VAS was a component of the Short-Form-McGill Pain Questionnaire (SF-MPQ), completed as a secondary efficacy variable. In the phase 4 study, VAS was the primary efficacy variable for measurement of pain intensity. Pain interference with sleep was evaluated using the BPI, which was one of the secondary efficacy endpoints in both the phase 3 and phase4 studies. Pain-associated BPI sleep interference (BPISI) was assessed on an 11-point numeric rating scale (NRS) ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep). Overall improvements on the PGIC were evaluated as secondary efficacy endpoints in phase 3 and phase 4 studies. The VAS and BPI were completed at the end of the baseline week, at Week 2, and at the end of the efficacy treatment period (Week 8 or 10) or early termination. The PGIC was completed at the end of the efficacy treatment period (Week 8 or 10) or early termination. For the integrated analysis, the end of the study was defined as Week 10 for phase 3, and Week 8 for phase 4.Efficacy analyses were performed for all patients who received ≥1 dose of study drug. Percent changes from baseline to the end of the study in VAS pain intensity and BPISI, and the proportion of patients categorized as “Very Much Improved”, “Much Improved”, “Minimally Improved”, “No Change”, “Minimally Worse”, “Much Worse”, or “Very Much Worse” on the PGIC at the end of the study were determined. Changes from baseline in VAS and BPISI scores were estimated with an analysis of covariance (ANCOVA) model that included treatment, study centers, and the baseline value as covariates. As last observation carried forward (LOCF) was the pre-determined method approved for all individual studies, missing data were imputed by LOCF to follow approved protocols. Exploratory analyses were designed to examine relationships among treatment outcomes for patients with potentially clinically significant responses to treatment with G-GR. Therefore, “Very Much Improved” and “Much Improved” responses on the PGIC were grouped together, and “Minimally Improved”, “No Change”, “Minimally Worse”, “Much Worse”, or “Very Much Worse” were grouped into “Not Improved”. Furthermore, in accordance with the published literature and the consensus summary statement produced by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) –26, reduThe integrated dataset from the phase 3 and 4 studies included 546 patients in the efficacy population and 556 patients in the safety population. Patient demographics and baseline disease characteristics were similar between studies Table . The mear = 0.28, p < 0.0001), whereas for patients with <30 % reduction in the VAS score, there was no linear correlation with BPISI  simultaneously reported ≥30 % reduction in the BPISI score (Table p < 0.0001).At the end of G-GR treatment, 53.7 % of patients in the efficacy population reported ≥30 % reduction in pain intensity on the VAS, 63.2 % of patients reported ≥30 % reduction in BPISI, and 46.3 % of patients reported feeling “Much” or “Very Much” improved on the PGIC Fig. . A compap < 0.0001) were “Much” or “Very Much” improved on the PGIC (Table p < 0.0001). In contrast, among patients with <30 % reduction in the VAS score, more were not improved than “Much” or “Very Much” improved on the PGIC . The relationship between percent reduction in the BPISI score and improvements on the PGIC was similar, and more patients with ≥30 % reduction than with <30 % reduction in the BPISI score  were simultaneously “Much” or “Very Much” improved on the PGIC . Baseline VAS values had a marginally significant (p = 0.0429) negative effect, and baseline BPISI values did not have a significant influence (p = 0.8458). Furthermore, percent changes from baseline in VAS and BPISI scores were both significant predictive factors for being “Much” or “Very Much” improved on the PGIC (Table p < 0.0001 vs. p = 0.0082). Because adding the interaction between percent changes in the VAS and BPISI scores to the regression model showed no significance (p = 0.4808) for being “Much” or “Very Much” improved on the PGIC  and in patients with epilepsy (32), a direct effect on sleep may have contributed to improvements in BPISI independent of pain reduction.No correlations were observed between BPISI and VAS for those with a ≤30 % change. This result may not be surprising, since a < 30 % change in VAS is considered minimally important; it is likely that any correlations, should they exist, are lost due to the very low signal.It is important to note that approximately 22 % of patients did not report clinically significant reductions in pain or BPISI but still reported feeling “Much” or “Very Much” improved on the PGIC at the end of treatment. These results suggest a complex relationship among patient-reported outcomes and that changes in other efficacy measures, such as mood, opioid usage, and return to work may also play a role. An analysis of pain reduction, pain interference with sleep, and PGIC in patients treated with placebo may also be of interest. In this study, since the phase 4 study was a real-world, open label study with no placebo control group, a rigorous analysis was not possible.Our results are consistent with a study of pregabalin in patients with diabetic peripheral neuropathy (DPN) or PHN that showed similar correlations between pain relief, sleep improvement, and improvements in quality of life, and these improvements were not solely mediated via control of pain or sleep disturbance . InteresFor the majority of patients with PHN and treated with G-GR in these clinical trials, clinically significant reductions in pain intensity and pain-associated sleep interference were correlated with, and independently predicted, feeling “Much” or “Very Much” improved at the end of the G-GR treatment. For optimal patient care, clinicians should consider reducing the impact of pain on quality of sleep as well as overall pain reduction.


There are patients who suffer from persistent dentoalveolar pain disorder (PDAP) which is a pain of the teeth, either dentoalveolar pain or nonodontogenic toothache, and its cause has not yet been identified. An effective intervention for PDAP has not yet been established. Interventions for patients with PDAP are generally pharmacological treatments such as antidepressants, anticonvulsants, and pregabalin. However, these medicines are not always effective for patients. The pain disorder in the orofacial region including temporomandibular disorder (TMD) and PDAP was effectively treated with our original exercise therapy. However, we did observe some intractable cases of PDAP even when our original exercise therapy was used. This paper presents our findings in which Kamishoyosan improved the pain intensity in 14 out of 15 PDAP patients refractory to our original exercise therapy. Patients suffering from tooth pain, either dentoalveolar pain or nonodontogenic toothache, of which the cause has yet to be identified, continue to seek pain treatment from several doctors, not only dentists but also several kinds of medical practitioners.Recently the name of persistent dentoalveolar pain disorder (PDAP) has been used to describe this kind of pain. PDAP is described as a pain that persists in the dentoalveolar region without any evidence of local disease –4. Much Kampo, traditional Japanese herbal medicine based on traditional Chinese herbal medicine, has been used to treat chronic pain in Japan . KamishoAfter obtaining approval from the Ethics Committee of Aichi Medical University for the review of the use and effect of Kampo medicine (reference number: 13-097), retrospective analysis from January 2012 to April 2013 was performed on 15 patients who visited the Multidisciplinary Pain Center (Pain Center) of Aichi Medical University. All patients were referred from other hospitals to the Pain Center because of PDAP. Treatment protocols used in the present report were based on institutional policy and clinical guidelines approved by the Ethics Committee of Aichi Medical University. The characteristics of the patients are described in After obtaining approval from the Ethics Committee of Aichi Medical University, we routinely explain to all patients that we record and store demographics, symptoms, course of pain, and medical record in all patients for possible future use in our research and then we obtain written informed consent at their initial visit to the Pain Center. We diagnosed each patient's condition as PDAP based on their medical histories and radiographic examinations. The intensity of pain was rated by the patients using a numerical rating scale (NRS) where 0 indicated “no pain” and 10 “the greatest pain possible.” The jaw movement test was evaluated using a cotton roll . We admi(1) Explanation. Firstly, we confirmed that there was no clinical and radiographic evidence of relevant pathology in their pain and explained this to the patients . The. The(2) (3) Psychological Intervention. We let patients understand that it was important to recognize both PAs and frequency of PAs during the daytime. Our only instructions were that when they felt pain, they had to recognize what kind of PAs they were doing and how frequently they were doing them. In addition, the patients were trained to relax their tongue, their masticatory muscles, and their jaw (heir jaw  9]. The. The(3)  P = 0.001). Intensity of pain improved in 14 out of the 15 patients. Although several patients reported that the pain did not completely disappear, if they felt any pain it was not at a level which caused them concern. Eight patients improved but three patients did not improve in jaw movement. No patient experienced any adverse effects during the medication. Although ten patients experienced recurrences of pain in about a year, Kamishoyosan provided an improvement of PDAP at each recurrence.The fifteen patients had not experienced any improvement in the intensity of their pain two months after commencing our original exercise therapy and PI . Thus, wA 48-year-old female had been suffering from severe spontaneous pain  and sensitivity to cold in the upper right maxillary first molar for 2 months. Firstly, we confirmed that there was no clinical and radiographic evidence of relevant pathology in her pain and explained this to her. She displayed jaw movement abnormality. She had not experienced any improvement in the intensity of her pain  two months after commencing our original exercise therapy and PI. She took 2.5 g of Kamishoyosan three times a day, while continuing the exercise therapy and PI to reduce parafunctional activities. The NRS dramatically decreased to 4 four days later and was 0 at day 11. Also, she improved in jaw movement. Although she experienced two recurrences of pain in a year, Kamishoyosan provided a quick improvement of PDAP at each recurrence.Many studies have reported the association between PDAP and TMD , 13. PatAlthough therapeutic algorithms for PDAP  include Kampo, or traditional Japanese herbal medicine, has been used for the treatment of not only chronic pain but also many other diseases in Japan. Kamishoyosan is a Kampo formulation used to effectively treat psychological symptoms such as anxiety, irritability, and depression –12. In tThere are several limitations in the present report. The present report is a small case series and not a nonrandomized control analysis of Kampo treatment. Another limitation is that the male-female ratio of PMDA is 1 : 9 in our clinical practice, so all 15 patients were female in the present report. Although Kampo medicines must basically be prescribed for patients based on patient-centered Kampo diagnosis, we did not see if the 15 patients matched with Kamishoyosan pattern. Thus, we need a prospective and comparative study that might be more appropriate to support a predictive, preventive, and personalized value of Kampo treatment.We treated 15 PDAP patients who were refractory to our unique exercise therapy to improve jaw movement and PI to reduce PAs through administration of the Kampo formulation, Kamishoyosan. Fourteen patients experienced a decrease in pain intensity after intervention. This finding suggests that the combination of Kampo and our exercise therapy was effective in treating PDAP.


ObjectivesThe purposes of this study are to assess the effectiveness of CyberKnife® stereotactic radiosurgery (SRS) in providing both initial and sustained pain relief for patients with both forms of trigeminal neuralgia (TN), assess potential prognostic factors, and examine treatment-related toxicities.Methods ® Patient Registry was screened for TN cases from July 2007 to June 2015. We evaluated initial pain relief achieved by examining changes in the Visual Analog Scale (VAS) scores following SRS. Prognostic factors relating to initial pain relief and the relationship between maximum dose (Dmax) and toxicity incidence were analyzed via univariate logistic regressions. We evaluated prognostic factors relating to sustained pain relief using the Kaplan-Meier method and log-rank analysis.The RSSearchResults Our analysis included 125 TN1 patients and 38 TN2 patients with initial VAS scores ≥ 3 treated at 16 community radiotherapy centers. Median Dmax for both cohorts was 75 Gy with a larger range for TN1 cases (67.42 Gy - 110.29 Gy) as compared to TN2 cases (70.00 Gy - 78.48 Gy). At initial follow-up, mean VAS scores after SRS were significantly lower for TN1 and TN2 patients (p < 0.0001). The vast majority of TN1 (87.2%) and TN2 (86.8%) patients experienced initial pain relief. Higher initial VAS scores (p = 0.015) were correlated with a greater likelihood of initial treatment success for TN1 patients. We did not identify any treatment or patient characteristics that had significant effects on initial pain relief for TN2 patients. Of the TN1 cohort, 28 of 125 patients reported follow-ups one year or greater after SRS. Twenty-three of 28 TN1 patients (82%) reported VAS scores of 1 or less at one-year follow-up, and eight of 11 patients (72%) had VAS scores of 1 or less at the two-year follow-up. No potential prognostic factors for long-term pain relief were significant. Roughly 18% and 11% of TN1 and TN2 patients, respectively, experienced acute toxicities , with the most common being sensory neuropathy, generalized pain, and nausea. Dmax > 75 Gy was not a predictor of toxicity incidence in TN1 cases (p = 0.597) but was significant for TN2 patients (p = 0.0009 following Fisher's exact test).ConclusionsSRS is an effective treatment option for TN patients in community settings. Initial pain relief following SRS was achieved in a vast majority of TN patients with associated minor toxicities observed in less than 20% of all patients. Trigeminal neuralgia (TN) is a chronic, debilitating pain condition of the trigeminal nerve, which provides widely distributed sensory innervation to the face. TN has an incidence of 12 per 100,000 people, disproportionately affecting the elderly and female patients [The first step in the management of TN is pharmacotherapy, such as carbamazepine, gabapentin, and oxcarbazepine. Side effects relating to these regimens include impaired memory, nausea, insomnia, confusion, and peripheral neuropathy -3. If su® stereotactic radiosurgery system (CK SRS).Stereotactic radiosurgery (SRS) has been a viable treatment option for TN since first being discussed by Leksell . SRS is ® Patient Registry, a multi-institutional international SRS/SBRT (stereotactic body radiation therapy) database with information on screening, treatments, and outcomes for over 15,000 patients, serves as an ideal resource to study the effectiveness of CK SRS for TN1 and TN2 management in community settings [The RSSearchsettings . Our goa® Patient Registry    [® is voluntary, and no compensation is provided to patients or participating centers. All principal investigators are provided RSSearch® protocols, case report forms, sample patient informed consents, and web-based training for data entry and database navigation. Local Institutional Review Board/Ethics Committee (IRB/EC) approval is required at all participating centers, and informed consent was obtained from all patients, as required by individual IRB/ECs, prior to data entry.Previous studies have described the methodology and design of the RSSearch885299)  . Partici® is a registry, there were no pre-defined treatment criteria. All patients were treated using the CyberKnife® Stereotactic Radiosurgery System. CyberKnife® is a frameless, image-guided SRS system consisting of a LINAC mounted on a 6-axis robotic arm that delivers a high dose of radiation to a lesion of interest while minimizing damage to adjacent healthy tissue. In situ x-ray images allow for head-tracking during procedures with non-invasive head immobilization to provide homogenous, non-isocentric, and conformal delivery of radiation doses to intracranial targets, such as the trigeminal nerve [As RSSearchal nerve .All patients were treated with single fractions of radiation with specific treatment planning based on varying institutional imaging, contouring, and treatment guidelines. Given the different definitions of prescription doses from multiple institutions in our study, all prescriptions were converted to maximum dose points (Dmax) to allow for uniform comparison across centers.Treatment outcomes were assessed using Visual Analog Scale (VAS) scores for facial pain that were reported before and after SRS. The VAS pain scale was chosen, given that the vast majority of centers participating in the RSSearch® elected to utilize VAS scoring when recording outcomes in the database. VAS scores range on a horizontal scale from “no pain” (scored as 0) to “pain as bad as it could be” (scored as 10) .Inclusion criteria for this retrospective study required that patients have information regarding Dmax, both pre-treatment and post-treatment VAS scores, and initial VAS scores ≥ 3. Following these criteria, a retrospective analysis of patients treated from July 2007 to June 2015 with TN1 or TN2 enrolled in the RSSearch® identified 163 total patients (125 patients with TN1 and 38 patients with TN2) treated at 15 centers in the US and one center in Australia.The initial response was defined as patients reporting a lower VAS score after SRS as compared to their pre-treatment VAS score. The majority of patients reported only one follow-up less than one-year post-treatment; for these patients, the post-treatment VAS score recorded at this visit was the one used for our analysis. If patients reported more than one follow-up less than one year after SRS, then the lowest post-treatment VAS score reported among all follow-ups was utilized to examine initial pain relief. To assess the effectiveness of SRS in providing initial pain relief, two paired t-tests were run for both TN1 and TN2 cases comparing pre-treatment and post-treatment VAS scores. Logistic regressions (or Fisher's exact test when logistic regression was not feasible) were used to screen for potential prognostic factors for initial pain relief and to examine the relationship between Dmax and toxicity incidence.Regarding long-term pain relief, a patient-reported VAS score > 1 at one-year follow-up or greater was defined as failure of sustained pain relief. Twenty-eight TN1 patients had a recorded VAS score one year or greater after being treated with SRS . Potential prognostic factors relating to sustained pain relief were evaluated using the Kaplan-Meier method and continuous log-rank analysis. All statistical analysis was performed using Stata 14.0 .Table Treatment characteristics and changes in VAS scores were examined. The results of this analysis can be found in Table CK SRS was successful in achieving initial pain relief in 87.2% of TN1 cases and 86.8% of TN2 cases. Roughly 6% and 8% of TN1 and TN2 patients, respectively, experienced no subsequent change in VAS score, and 7.2% and 5.3% of these same populations had pain progression at their last reported follow-up. Average declines in VAS scores were 5.62 (95% CI: 4.93 - 6.32) for TN1 cases and 5.05 (95% CI: 3.82 - 6.29) for TN2 cases, with the distribution of changes in VAS scores (post-treatment VAS - pre-treatment VAS) following CK SRS shown in Figures We next moved on to identify potential prognostic factors regarding initial treatment response. Factors, such as initial Karnofsky Performance Score (KPS), initial VAS score, age, gender, and Dmax, were examined via univariate logistic regressions. The results of these findings can be found in Tables We also examined how effective CK SRS was in providing relief of TN-related symptoms for patients reporting follow-ups of one year and greater and if any prognostic factors could predict longer term treatment success. The Kaplan-Meier curve of TN1 patients who reported follow-ups greater than one year can be found in Figure In Table Six TN2 patients had follow-ups of greater than one year, and 2/6 TN2 patients reported VAS scores lower than pre-treatment assessments. At the two-year follow-up, 0/3 TN2 patients had lasting pain relief. Given the inadequate number of patients that had follow-ups in the TN2 cohort, a Kaplan-Meier analysis was not performed.Treatment-related side effects were also examined. A summary of specific toxicities can be found in Table Using univariate logistic regression, we examined whether patients treated with Dmax > 75 Gy had a higher likelihood of experiencing treatment-related toxicities. In TN1 cases, we found that Dmax was not a predictor of toxicity incidence (p = 0.597). However, for TN2 cases, we were unable to run the regression as all four patients that had reported acute toxicities were treated with radiotherapy plans of Dmax > 75 Gy . TN2 patients that were treated with Dmax ≤ 75 Gy reported no acute toxicities (p = 0.0009 following Fisher's exact test).TN is a chronic disease, and for many patients, pharmacotherapy may not provide therapeutic relief of symptoms. As such, patients have a variety of treatment options, notably rhizotomies, MVD, and SRS. SRS is a non-invasive alternative for TN treatment and may be especially helpful for patients who are unable to undergo anesthesia for MVD or would prefer not to undergo elective surgery. Notably, previous studies have found that CK SRS may be more cost-effective than MVD  with similar clinical effectiveness with regards to initial pain relief .This retrospective study included 163 TN patients (125 TN1 patients and 38 TN2 patients) with initial VAS scores ≥ 3. Our study is unique in its multi-institutional observation of both TN1 and TN2 patients, the exclusive use of the CyberKnife® Radiosurgery system, and examination of treatment outcomes in community settings. Consistent with the literature, TN was more common in older female patients . Of noteWith regard to initial pain relief, our analysis found that roughly 87% of both TN1 and TN2 patients responded favorably to CK SRS. These results seem to fall in line with the literature. Short-term response rates in studies utilizing CK SRS have historically ranged from 67% to 88% -22. GK SWe also examined long-term pain relief following CK SRS for TN1 patients. Twenty-three of 28 patients (82%) reported a VAS score of 1 or less at one-year follow-up, and eight of 11 patients (72%) reported a VAS score of 1 or less at the two-year follow-up. Two of five patients (40%) of the TN1 cohort reported lasting pain relief at the three-year follow-up. However, estimates of long-term pain relief at the three-year follow-up are quite unreliable given the very low sample size (95% CI for pain relief at three years ranged from 10% - 75%) and, thus, should be cautiously interpreted. This is especially relevant given the retrospective nature of our study and the possibility that patients may be more likely to return for subsequent follow-ups due to the lack of sustained pain relief. As such, our findings may underestimate the long-term therapeutic benefit of CK SRS. Our findings at the two-year follow-up are similar to the findings of Karam, et al., who found that at the 28 month follow-up 72% of TN patients treated with CK SRS had freedom from severe pain  following a mean prescription dose of 64 Gy . Of noteWe identified no treatment or patient characteristics that could predict a greater likelihood of longer-term pain relief following treatment. Of the prognostic factors examined regarding long-term pain relief by Karam, et al., diabetic patients were found to have significantly poorer outcomes  . SimilarRoughly 18% and 11% of TN1 and TN2 patients, respectively, reported acute toxicities with sensory neuropathy  being the most common in both cohorts. Similar to other studies, no major adverse effects were noted following CK SRS, with all acute toxicities reported being either RTOG Grade 1 or Grade 2. Other CK and GK SRS studies have noted hypesthesia and facial numbness to be the most common complications in anywhere from 10–50% of patients , 28-30. There are several limitations to our study that merit mentioning. First, the retrospective nature of this analysis, as well as the low sample size of patients that had long-term follow-up, lowers the power of our findings. This was particularly true for our TN2 cohort, as we were unable to perform a Kaplan-Meier analysis to examine prognostic factors for sustained pain relief, given the lack of follow-up after one year for the vast majority of patients. Another limitation of our study is the potential for underreporting, as may be the case with side-effects, again due to lack of routine long-term follow-up. We are also unable to discuss the mean latency to response as has been done by other studies in the literature, given a lack of uniform and standard follow-up of patients in our cohort. With regards to measurement of pain, we ideally would have used the Barrow Neurological Institute (BNI) pain intensity scoring. However, a very limited number of patients (six TN1 patients and one TN2 patient) reported both pre-treatment and post-treatment BNI scores. Though it is a validated tool for quantification of pain, VAS scoring is inherently a subjective outcome measure as it relies on and is susceptible to individual interpretation and variation. However, given the fact that VAS scores were only compared for each individual patient as opposed to comparing VAS scores between different patients, the subjective nature of the pain scoring is less concerning. Finally, no information was available regarding patient comorbidities  that could have been examined to better define and characterize prognostic factors.This study demonstrates the effectiveness of CK SRS in providing safe and effective pain relief as an alternative to invasive surgical procedures following medication failure with no major adverse toxicities reported. Prospective studies are warranted to determine prognostic factors regarding long-term pain relief following CK SRS as well as better defining optimal radiotherapy planning and dosing.


Patients with cervical radiculopathy often have neck- and arm pain, neurological changes, activity limitations and difficulties in returning to work. Most patients are not candidates for surgery but are often treated with different conservative approaches and may be sick-listed for long periods. The purpose of the current study is to compare the effectiveness of neck-specific training versus prescribed physical activity.The current protocol is a two armed intervention randomised clinical trial comparing the outcomes of patients receiving neck specific training or prescribed physical activity. A total of 144 patients with cervical radiculopathy will be randomly allocated to either of the two interventions. The interventions will be delivered by experienced physiotherapists and last 14 weeks. The primary outcome variable is neck- and arm pain intensity measured with a Visual Analogue Scale accompanied with secondary outcome measures of impairments and subjective health measurements collected before intervention and at 3, 6, 12 and 24 months after base-line assessment.We anticipate that the results of this study will provide evidence to support recommendations as to the effectiveness of conservative interventions for patients with cervical radiculopathy.NCT01831271ClinicalTrials.gov identifier:  Cervical radiculopathy is mainly the result of cervical disc herniation or spondylosis which results in nerve root inflammation, impingement or both. Cervical radiculopathy has an annual incidence rate of 83.2 per 100,000 in the general population [Patients with cervical disc herniation and/or spondylosis suffering from cervical pain and radiculopathy are often treated conservatively . If the The studies evaluating physical treatment for patients with cervical radiculopathy are of various quality , 13–22. Today, in clinical practice, the waiting times for patients with cervical radiculopathy to be evaluated by a surgeon are long and most of the patients are not surgical candidates. Many patients are therefore sick-listed for long periods of time with various treatment approaches or without any treatment at all. It has been suggested that a structured physiotherapy program should precede surgical intervention , 13 but The purpose of this randomised clinical trial will be to compare the effects of a neck-specific exercise program including a cognitive behavioral approach with prescribed, self-mediated and progressive physical activity approach in patients with cervical radiculopathy. We will include outcome assessment before and after the interventions at 3 and 6 months and 1- and 2 years post base-line.In a prospective, randomised clinical trial with follow-up at 3 and 6 months, and 1- and 2 years 144 patients with cervical radiculopathy will be included. The study will follow the CONSORT guidelines  and has Patients with cervical pain and radiculopathy referred to the Neurosurgery Clinic at the Karolinska University Hospital will be invited to participate. A total of 144 consecutively selected patients will be included. Before inclusion all patients will undergo a standardized physical examination by a physiotherapist which will include a medical history, pain, sensory changes, reflexes, range of motion and muscle strength tests. Inclusion criteria are: 1) Magnetic Resonance Imaging (MRI) verified cervical disc disease showing cervical nerve root compression and 2) neck- and/or arm pain verified with a neck extension test or a neurodynamic provocation test positive Spurling test . ExclusiThe sample size is based on data from the “Swedish neck study” , 13. A sAfter the baseline assessment, each patient will be randomised to one of two interventions: A) active physical rehabilitation with a neck specific exercise program including a cognitive behavioral approach (neck-specific training) or B) prescribed, self-mediated and progressive physical activity . See flow chart Figure . RandomiGroup allocation will be concealed until the baseline measurement is completed. The patient will then receive a sealed envelope containing the group allocation. Blinding of the patients, the test leader and the treating physiotherapists participating in the study is not possible. First, because it will be obvious to the patient which the type of intervention they will receive and secondly, because the test leader also serves as contact person for the patients enrolled in the study and the patients could disclose their group assignment. To prevent bias from not blinding the two intervention arms would not be provided by the same physiotherapist or even the same geographical location i.e. prescribed physical activity would be given by physiotherapists other than those giving the intervention neck-specific training. The data transformation from paper questionnaires and physical examination protocols into data files will be handled by an independent person otherwise not involved in the study.Background data that will be collected at the first visit of the study will include: gender, age, social situation, smoking habits, back pain, pain medication, pain history related to the neck problems, previous medical problems , earlier treatments for the neck problems and its effects, work situation , and physical activity/ exercise habits.Clinical measurements that will be performed by an independent, blinded examiner before intervention, and at 3, 6, 12 and 24 months follow-up periods: Neurological examination, cervical range of motion [f motion , neck muf motion , hand stf motion  and balaf motion , 33. TheQuestionnaires used have good reliability and validity (listed under secondary outcome measures). The questionnaires will be administered before intervention, 3, 6, 12 and 24 months after the start of the intervention.The primary outcome measure is pain intensity. Intensity of neck pain and arm pain is measured on a Visual Analogue Scale (VAS) (0–100 mm) , 35. PaiAdditionally, the character of pain, number of pain locations and distribution of symptoms will be evaluated with a body diagram. Neck specific disability will be measured by the Neck Disability Index , 37. HeaAdditional questions of fulfillment and satisfaction which will be asked after the intervention at the 6 and 24 months follow-ups such as: -adherence to the intervention, -treatment expectations fulfilled, - if they would recommend the intervention to patients with similar problems and if surgery or other interventions have been undertaken.To guarantee the patients’ confidentiality all data collected will be coded and the codes will be locked in and stored separate from collected data.Each physiotherapist who will treat patients in the study has been trained in the intervention program by the test leader who is a specialised physiotherapist at the specialist clinic. The entire treatment approach is documented in a manual of standard operating procedures and given to the treating physiotherapist. All exercise performed and progression of each will be registered in a diary. The written information is also available for the patients. For both groups the intervention period is 14 weeks.Active physical rehabilitation including neck-specific training with an additional cognitive behavioural approach will be included. The goal of the intervention is to improve physical functioning with specific respect to sensorimotor function, neck muscle strength and endurance as well as reducing pain. The active physiotherapy rehabilitation program consists of a standardised program (three times a week) with medical exercise therapy and if needed vestibular rehabilitation. At the start of the intervention motivational interviewing will be included. Additionally once a week during the first 14 weeks of the program (Week 1–14) the physiotherapist will educate the patient about physiology of pain, stress, exercise, breathing, relaxation, coping, pacing and ergonomics. The physiotherapist will also teach and have a discussion with the patient on how to manage the pain at home both physically with; heat, cold or TENS and psychologically with; relaxation training, exercises for increased body awareness as well as goal setting for better coping strategies and self-efficacy. Throughout the treatment program a cognitive approach from the physiotherapist according to theoretical behaviour change models will be used. Home exercises will also be prescribed. All physiotherapists will be provided with a well-defined frame of exercises with a standardised and structured progression. After a clinical examination the physiotherapist adjusts the program for each patient according to the selection of exercise and dosages chosen. From week 15–20 the patients have the opportunity to meet the physiotherapist for discussion, encouragement and help with exercise progression and otherwise do exercise on their own in the clinic or at home.Physical activity will be formally prescribed by a physiotherapist and followed up according to customary routines , 54. PreThe interventions will be led by experienced and specialised physiotherapists. The patients in the neck specific training group will have personal contacts with their physiotherapist whereas in the prescribed physical activity group they do not have scheduled regular contacts but the opportunity to contact the physiotherapist when needed. An earlier study of patients after lumbar disc surgery showed good results for an intervention based on home training when patients have received careful instructions and have access to the physiotherapist if questions arise .Outcome data from the two groups will be compared using an intention to treat analysis with all patients being analysed in the group to which they were originally randomly assigned even though they are lost to follow-up or non-compliance of the intervention or any other deviation from the protocol . In the The importance of the study for patients with cervical radiculopathy as well as society is significant as these individuals often experience severe, neuropathic pain resulting in both great personal and social costs. Many patients are sick-listed for long time periods.The current study aims to supplement knowledge as to optimal treatment for patients with cervical radiculopathy. Treatment with surgery is also an identified knowledge gap in DUET  however not primarily addressed in the current study but could be effected secondarily as fewer patient might need surgery. The long-term effects of the study could potentially reduce the time of sick leave and improve the rate of patients returning to work and/or former activity by optimising treatments. Furthermore it may decrease the number of patients who will require surgery for their neck problems and thus reduce the mental, physical and societal costs.The current trial is designed to minimise biases of risk in clinical trials by using randomisation, concealed allocation of patients, specified eligibility criteria and an intention to treat principle in analysis of the data. However, a complete blinding of the patients or the treating physiotherapists is not possible due to the types of intervention where it is obvious which kind of treatment one is receiving. Another potential limitation is that the study does not contain a true control or placebo group. The current patient group have pain and they are referred to the hospital due to their pain and significant findings on MRI. We potentially could have them on a waiting list for 14 weeks but that might result in increasing pain and disability. It would therefore not be ethical to assign some of them to a non-treatment group. Since there is minimal evidence and no consensus of how to best manage patients with cervical radiculopathy there exists considerable variation in what is currently being performed. The treatment differences which will occur in the current study are consistent with those sometimes used in clinical practice.This study uses a randomised clinical trial design to investigate the effectiveness of two types of conservative treatments for patients with cervical radiculopathy. The study will also investigate clinical features for possible prediction of a patient’s response to each treatment. The findings will enable evidence-based recommendations as to the effects of conservative interventions for patients with cervical radiculopathy. Furthermore, findings will provide direction for future research and treatment rationale for the patient population.


Despite high prevalence of diabetic peripheral neuropathy there is no definite treatment for the condition. The present study was conducted to assess the efficacy of transdermal nitroglycerin patch in pain control of patients with DPN.This randomized, double-blind, crossover study was conducted on 30 patients with symmetric distal peripheral neuropathy and good glycemic control. The patients were randomly assigned to receive nitroglycerin transdermal and placebo patches in two 4-week stages. The severity of pain and other neuropathic sensory symptoms were assessed at the end of each course.p = 0.048) at least during the first phase of the study. Except for mood and sleep, a significant reduction in all Brief Pain Inventory scores was noted in the drug group . SF-MPQ also showed the drug patch to be effective in improving different aspects of pain measured using McGill Pain Questionnaire, except for Role–emotional.Mean reduction of pain severity was more prominent in the NTG group compared to placebo group of the study (It could be concluded that nitroglycerin plasters can effectively help alleviate pain in patients with diabetic neuropathy.IRCT201308223213N1 About 220 million individuals suffered from diabetes in 2010; the rate is expected to increase worldwide and reach 366 million in 2030 [The condition, mostly characterized by distal symmetrical symptoms and signs of sensory and/or motor impairment, is frequently underreported 12.5 %) and more frequently undertreated (39 %) . DPN rep % and moThere are several patterns of peripheral neuropathy based on the cause or size of predominant fiber involvement. The most common form is symmetrical peripheral neuropathy. Despite its high prevalence, there is no definite treatment for the condition. Several controlled studies have demonstrated that painful DPN can be relieved by antidepressants, anticonvulsants, tramadol, opioids, topical medications , aldose reductase inhibitors, and protein kinase C beta inhibitors –9. UnforThe pathophysiology of the condition remains unclear, although it is associated with peripheral demyelination, a reduction in peripheral nerve conduction, and degeneration of myelinated and unmyelinated sensory fibers . In manyRecent data suggest that impaired neuronal generation plays an important role in the pathogenesis of DPN either through inducing hyperalgesia or contributing to a reduction in endoneurial blood flow in diabetic patients with peripheral sensory neuropathy –14. In tIn view of the fact that the ISDN spray is not available worldwide, Rayman et al. used glyceryltrinitrate (GTN) patches and showed it to be effective in reducing neuropathic pain in diabetic patients in a non placebo-controlled study . The preThis randomized, double-blind, crossover study was approved by the Ethical Board Committee of Diabetes Research Center of Tehran University of Medical Sciences (registration number: 00185). Eligible subjects included adult type 1 and type 2 diabetic patients with stable diabetic control not on any other medications for their neuropathic pain, visiting diabetes clinics of the Endocrinology and Metabolism Research Institute between May and September 2012. All the patients signed an informed consent form.The patients were selected from among those referred to our diabetes clinic with symmetric distal peripheral neuropathy. None of the patients showed any indication that they had central, nociceptive, or psychogenic pain. Patients’ demographic data along with information on their type and duration of diabetes, time of onset of diabetic neuropathy were recorded in a questionnaire. Patients with erratic glycemic control defined as HbA1c levels higher than 8.5 % (69 mmol/mol), positive history of ischemic heart disease, peripheral arterial disease with absent foot pulses, active diabetic foot ulceration in the legs or a positive history of lower extremity amputation, and peripheral neuropathy secondary to other diseases such as hypothyroidism, vitamin B12 or folate deficiency, sarcoidosis and alcoholism were excluded. Subjects on concurrent vasodilator (sildenafil or nitroglycerin) therapy, those who had started taking insulin in the past month, or consumed medications with approved interaction with nitroglycerin were also excluded. Patients with pressure index ratio of ankle systolic pressure  to brachial systolic pressure values lower than 0.8, which signified peripheral arterial disease as the cause of pain, were also excluded.http://www.algeos.com/neurothesiometer.html)Upon arrival, a thorough neurologic physical examination and neurothesiometeric assessment were performed to confirm the presence of diabetic neuropathy , and distal bilateral muscle weakness or atrophy, bilateral decrease, or loss of tendon reflexes. In all cases, the diagnosis was verified by nerve conduction velocity, electromyography, and/or quantitative sensory tests.Fasting venous blood samples were collected for the measurement of HbA1c at baseline and at the end of the study. Thyroid and liver function tests were performed at baseline to exclude other causes of neuropathy.Considering the power of the study as 80 % (type II error = 0.2), remission rate of 44 % in the case group compared to 5 % in the controls, 23 patients were needed in each group. The patients were randomly assigned to start either in the drug or in the placebo limb of the study and after a washout period they were crossed over for receiving the treatment of the other group. Thereafter, taking into consideration the crossover nature of the study and possible 20 % loss to follow up rate, 30 patients were recruited in the study.The patients were randomly assigned to receive nitroglycerin transdermal patch  and placebo patches in two stages based on the odd and even number of their unit numbers. The patches were recommended to be applied once a day, worn for 12 to 14 h, and then removed. The patients were recommended to apply the patches to clean, dry and hairless skin, and choose a different area each day based on a cyclic pattern .The patients were randomized to start the study either with drug (DP) or placebo (PD). Based on the groupings, the first phase of the treatment was started. After 4 weeks, there was a 3 week washout period during which the patients of either group were asked to taper the treatment by using the patches every other night at the first week and stop application of the patches for the next two weeks. Thereafter, the patients exchanged their treatment for a further 4 weeks. The patients and investigators were unable to distinguish between the patches as they were identical. No major changes in diabetic or pain management regimen were made before and throughout the study.The severity of pain was assessed using 10-score Numerical Rating Scale (NRS) biweekly, where 0-no pain at all and 10-the most severe pain ever experienced. Those with NRS scores lower than four at baseline were excluded. The treatment efficacy was defined as 30 % and 50 % difference between the final score and the baseline score in NRS scoring for each treatment phase. Allodynia was assessed with suprathreshold testing method by using one of the largest Semmes-Wienstein monofilaments (6.10) and asking the patients to report the severity of pain according to a 3 point scale of mild, moderate and severe. Other neuropathic sensory symptoms  were also recorded as no symptom: 0, mild: 1, moderate: 2, or severe: 3 on a 3-cm Likert scale.At the end of each treatment phase, functional health and pain were assessed using SF-36 Health Survey and Brief Pain Inventory questionnaire (BPI), respectively. Beck Depression Inventory Score System (BDI) and standard seven-point Patients’ Global Impression of Change (PGIC) scale helped with depression and satisfaction evaluation at the same intervals.The study assistant, an expert nurse unaware of the study objectives, called the patients twice a week and asked them about possible occurrence of pain and other adverse effects, its severity and duration at the end of each phase. Patients experiencing severe headache as a complication of nitroglycerin were excluded. Using a questionnaire, the patients were asked to report the influence of these adverse effects on their life. The study assistant also asked the patients regarding their satisfaction about the treatment, possible confounding use of analgesics or other rescue drugs. The patients were asked to visit the clinic at the end of each phase, during which he/she underwent a thorough physical examination.p-value less than 0.05 was considered statistically significant.Continuous variables are expressed as mean (SD) when the distribution was normal or median (interquartile range) in the case lack of normal distribution. Categorical data are expressed as percentage. The normal distribution of continuous data was assessed by - Lilliefors’ test and due to lack of normality comparison of mean differences of the Beck Depression Inventory, Brief Pain Inventory and SF-MPQ parameters between drug and placebo groups were assessed by Wilcoxon Signed Rank test. Repeated measure ANOVA was used to compare the NRS at different intervals. The percent of patients’ allodynia and percent of PGIC reduction in study groups were assessed using Chi-square test. The gathered data were analyzed by SPSS ver. 15. A From among the 30 individuals recruited in the study, 10 did not complete the research, eight of them because of the adverse effects of the drug. Two others however, left as they were not willing to continue  . Similarly, except for mood and sleep, a significant reduction in all Brief Pain Inventory scores was noted in the Drug group    Fig. . The meap value = 0.006). The standard seven-point Patients’ Global Impression of Change (PGIC) scale showed that 80 % (95 % CI: 56 %–94 %) of the patients were satisfied with using the drug. As for the placebo group, the rate was as low as 20 % (95 % CI: 5.7 %–43 %) .Using Beck Depression Inventory score system, the drug was reported to be effective in relieving depression associated with diabetic neuropathy  and those with a probable added influence  , 20. GooIn the absence of curative therapy, the main aim of management is to provide symptomatic pain control using pharmacological and non-pharmacological agents, and to preserve good glycemic control . The besAs for the anticonvulsants, the use of phenytoin and carbamazepine has shown promising results. Phenytoin however is problematic in diabetics due to its inhibitory effects on insulin secretion and long-term carbamazepine may cause serious hematologic side effects , 24. TheGabapentin is widely used to treat DPN as despite being effective in reducing pain it has fewer troublesome side effects and almost no drug interactions , 27. UnlNowadays, tramadol, a centrally acting, synthetic, non-narcotic analgesic, is commonly used for the treatment of moderate to moderately severe pain, even chronic pain in diabetic neuropathy . DespiteAntagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor such as Dextromethorphan are also reported to be effective in reducing pain of diabetic neuropathy but not postherpetic neuralgia . DuloxetRecently, Yuen et al. for the first time used isosorbide dinitrate (ISDN) spray to reduce pain in DPN subjects . They reIn the present study transdermal nitroglycerin patches were used to combine the effectiveness of nitroglycerin as reported in the Yuen study and transdermal patches as noted by Rayman. Our study showed that these patches reduced pain during the pre-washout period. After this washout interval the difference was not significant (maybe due to loss of about one third of the participants mainly because of drug side effects). At the same time most patients experienced some general improvement and well-being. While our study failed to assess different types of pain separately, we reported that patients experience more pain of any type while using the placebo. Moreover, our study revealed that nitroglycerin is more effective in reducing physical pain than improving the mental status of the patients, pointing out the complicated nature of chronic pain and need for multi-aspect treatment of the condition .The main limitation to the use of these plasters is the high rate of side effects experienced by the consumers, a condition which made a large number of our subjects leave the study and may overestimate the obtained results. This is also in line with the result of previous studies which have reported headache in 52 % of nitroglycerin users.It could be concluded that nitroglycerin plasters can effectively help alleviate pain in patients with diabetic neuropathy. Further studies with larger patient numbers are required to confirm the findings of this study, and determine whether the effects are sustained. Moreover considering the promising results of this study, the effect of these plasters on diabetes status is an issue of concern and needs to be studied in the future.


Total hip arthroplasty (THA) is a common procedure associated with moderate postoperative pain. No nerve block without loss of motor function has been documented for THA. We hypothesised that an ultrasound-guided lateral femoral cutaneous nerve (LFCN) block added to a multimodal postoperative pain regimen would reduce postoperative pain after THA.One hundred patients who had a THA by the posterior approach were evaluated in this randomised, placebo-controlled, blinded, parallel-group trial comparing an ultrasound-guided LFCN-block with either 8 ml of ropivacaine, 7.5 mg/ml, (Group Ropivacaine) or 8 ml of saline (Group Placebo) given postoperatively. Surgery was performed under spinal anaesthesia. The primary outcome was pain ) 4 h post-blockade during 30° flexion of the hip. Secondary outcomes were pain at rest, pain during movement, oxycodone consumption (0–24 h), time to mobilisation, ability to mobilise, and length of stay. Patients, assessors and all staff involved with patient care were blinded to the intervention.p = 0.41; difference −5 mm (95 % CI: −15 mm - +5 mm). No differences in any of the secondary outcomes were observed. No adverse events, or harms, were observed during the trial.There was no difference in primary outcome between Group Ropivacaine and Group Placebo EudraCT:  There is no gold standard for pain management after total hip arthroplasty (THA) , 2. EarlWound pain may play a role in pain after THA. It has been demonstrated that the size of the incision is directly related to postoperative pain and minimal incision THA is shown to reduce postoperative pain , 5. LocaPeripheral nerve blocks used for postoperative pain management after THA include femoral nerve block, fascia iliaca block and lumbar plexus block . All havThe lateral femoral cutaneous nerve (LFCN) is a sensory branch from the lumbar plexus and has a highly variable course and supplies parts of the lateral and anterior upper thigh –15. The The aim of this placebo controlled trial was to investigate the effects of LFCN-block on pain, opioid requirements and mobilisation in patients receiving a basic analgesic regimen consisting of paracetamol and ibuprofen after THA. We hypothesised that LFCN-block would reduce pain during movement 4 h after LFCN-block (primary outcome) without delaying mobilisation.This prospective, randomised, placebo-controlled trial was approved by the Danish Medicine Agency, , the local Regional Ethics Committee, Region Zealand, Allén 15, 4180 Sorø,  and the Danish Data Protection Agency. The Copenhagen University Good Clinical Practice Unit monitored the trial. The trial was conducted at Næstved Hospital, Næstved, Denmark and registered at clinicaltrials.gov (NCT02289937) on November 12th 2014.All patients provided written informed consent before participating. Eligible participants were patients scheduled for primary THA under spinal anaesthesia. Exclusion criteria were general anaesthesia, allergy against local anaesthetics, revision arthroplasty, bilateral arthroplasty, fertile women and patients with daily use of opioids.Randomisation was based on a computer-generated randomisation list, in a ratio of 1:1. The randomisation list and sealed, opaque envelopes were made by a secretary with no further involvement in this trial. Upon inclusion, subjects received treatment assigned according to the randomisation list, in consecutive numbered, opaque, sealed envelopes.The study medication was prepared by a nurse according to the randomisation list. This was verified by a second nurse. These nurses were not further involved in treating the patient, or in the trial. The study medication was prepared in a syringe and labelled with the patient’s id-number and the number according to the randomisation list. Ropivacaine and saline are visually indistinguishable.All investigators, patients, outcome assessors, and clinical personnel were blinded to the intervention.All subjects received a primary hip arthroplasty. This was either cemented, uncemented or hybrid using the posterior approach. No LIA was used. The subjects were anaesthetised with spinal anaesthesia induced with 2–2.5 ml isobaric 0.5 % bupivacaine. Sedation with propofol or remifentanil was administered at the discretion of the anaesthesiologist. In the case of failure of the spinal anaesthesia and conversion to general anaesthesia the participant would be removed from the trial and replaced.The LFCN-blocks were performed in the post anaesthesia care unit when the subjects were able to move their toes but before the spinal anaesthesia had worn off (defined as T0). The subjects received an active or placebo LFCN-block according to randomisation. The LFCN-blocks were performed by anaesthesiologists specially trained and certified to the procedure.A high-frequency linear ultrasound transducer 15–6 MHz) was used to scan the area (Sonosite S-nerve). The study medicine was administrated as a bolus of 8 ml 7.5 mg/ml ropivacaine or 8 ml isotonic saline. We identified the LFCN between the fascia lata and the fascia iliaca , or when requested by the patient. The opioid used was oxycodone, either orally or intravenous.The primary outcome was difference in pain between the groups during 30 ° flexion of the hip at four hours after T0 (T4). Secondary outcomes were pain at rest and during 30 ° flexion of the hip at T0, T1, T2, T4, T8, T12 and T24 , cumulative oxycodone consumption (0–24 h postoperatively), time to first administration of oxycodone, length of hospital stay, time to mobilisation and ability to mobilise.We assessed pain with the VAS-score  at rest and during 30 ° active flexion of the hip. The mobilisation ability was assessed using the Cumulated Ambulation Score  , 17. OpiA difference of 20 mm in VAS-scores at T4 during 30 ° flexion of the hip between the two groups was considered clinical relevant. From the literature we found a standard deviation (SD) of 30 mm . With a p < 0.05 was considered statistical significant. Bonferroni correction was used for multiple comparisons.Data were analysed using IBM SPSS Statistics version 21 for Windows . We used Shapiro-Wilks test to test for normality of our data. Data are presented as mean and SD, or median and first and third quartile as appropriate. For comparison of our non-parametric data we used Mann-Whitney U-test and the Hodges-Lehman estimator. A two-sided After completion of the trial the data were typed into a spreadsheet by two investigators and compared for typos. A randomisation list assigning subjects to either group “a” or “b” was provided without revealing the identity of the groups. The statistical analysis had been performed and conclusions were drawn before it was revealed which group was ropivacaine and which was placebo.One hundred twenty subjects were enrolled in the study from 3rd of March 2014 to 1st of October 2014 in order to reach the pre-specified number of 100 patients because 20 did not complete the study , Due to unforeseen difficulties obtaining data for all subject we had only few VAS-scores for T8 and T12. Data for VAS-scores are seen in Figs. http://pro.medicin.dk/Laegemiddelgrupper/Grupper/227010#a300). The median intravenous-oxycodone consumption was 7 mg (2–13) and 6 mg (2–9), p = 0.12 in the ropivacaine group and the placebo group, respectively. There was no difference in the time to first opioid-administration between the two groups  (p = 0.26) or time to first mobilisation .There were missing values for 40 subjects with respect to the mobility assessment . Of the remaining 60 subjects there were no differences in mobilisation ability . The main reason for this was unforeseen staff shortage on the ward. Furthermore, many patients were asleep and we decided not to assign a specific VAS-score to a sleeping patient. We have chosen not to show the pain scores for these time points and not to calculate the Area Under the Curve (AUC) for the first 24 h because of the lack of data. This is an obvious drawback of this study, but we believe that it does not alter the conclusion of our study due to the fact that we observed no differences at T0, T1, T2, T4, and T24.Another explanation for the lack of significant differences in pain is block failure. No sensory testing was performed in this trial. Sensory testing is routine practice at our institution, but we decided not to perform this in order to avoid unblinding the trial. Block failure is a rather unlikely explanation because the LFCN-block is fairly easy to perform, with a high success rate and was executed by few anaesthesiologists who were trained and certified for the procedure.A number of anatomical variations of LFCN has been described –13, and In conclusion, we demonstrated no additional analgesic effects of a lateral femoral cutaneous nerve-block when combined with a basic analgesic regimen with paracetamol, ibuprofen and oxycodone after THA by posterior approach. Further studies are needed to investigate the effect of the LFCN-block among patients with higher pain scores.


Background. Pain is commonly experienced following surgical procedures. Suboptimal management is multifactorial. Objectives. The primary objective was to assess whether patients used a device (Navimed) to self-report pain over and above a normal baseline of observations. Secondary outcome measures included comparison of pain scores and patient use of and feedback on the device. Methods. In a prospective randomized controlled trial, elective gynaecological surgery patients received standard postoperative pain care or standard care plus the Navimed, which allowed them to self-report pain and offered interactive self-help options. Results. 52 female patients, 26 in each of device and standard groups, did not differ in the frequency of nurse-documented pain scores or mean pain scores provided to nurses. The device group additionally reported pain on the device  = 2.75, p < 0.001) that was significantly worse than reported to nurses but retrospectively rated significantly less anxiety. 80% of patients found the device useful. Discussion and Conclusion. This study demonstrates that patients used the Navimed to report pain and to help manage it. Further work is required to investigate the difference in pain scores reported and to develop more sophisticated software. Moderate to severe acute pain is commonly experienced in medical and surgical patients. Pain management in inpatient settings is hampered by shortcomings in pain assessment and delays in pain treatment . DevicesPsychological factors also form a key part of pain experience . They exProviding patients with procedural information during an intervention reduces pain scores, total analgesic use, and length of hospital stay . The mosThere is also evidence that relaxation techniques, which can be delivered by audio or written instruction, as well as imagery and music, have an adjuvant role in alleviating pain. Relaxation focuses on reducing muscle tension and calm breathing techniques; music may induce these but is also distracting and may reduce subjective awareness and distress . There aAttention diversion techniques can also modulate pain experience. Audio or visual stimuli may be used to achieve this and can also be used concomitantly alongside relaxation techniques already discussed . A CochrThe Navimed introduces nonpharmacological management of pain into the clinical environment, under the patient's control, with the intention of providing the means to self-report pain whenever the patient wishes; to provide procedural information available at any time; and to provide relaxing and attention diverting resources to help manage postoperative pain. The choice of attention diverting resources was based on discussion with pain management clinicians.Existing applications rely heavily on providing information or on single modality strategies, and none have been formally evaluated . A recenA prospective, unblinded, randomised controlled trial was carried out at a large London teaching hospital. Patients were selected, as per the inclusion criteria, and consented at routine surgical preassessment visits at the hospital.Patients were randomised by a researcher not involved in the allocation process, by sealed envelope, to receive standard postoperative care (Group S) or standard postoperative care plus a handheld device Navimed (Group D). The patients in Group D were instructed preoperatively how to use the Navimed and familiarised themselves with a training version in the presence of a researcher. They were issued with their own device in recovery when fully awake postoperatively and reminded again how to use it. The trial started once the participant was transferred to the surgical ward.Both Group S and Group D had their pain scores recorded by nursing staff at 4 hourly intervals in accordance with hospital guidelines using a 0–4 scale with the verbal labels none, mild, moderate, severe, and very severe. Group D could also report pain scores on the device as frequently or infrequently as they desired on a 0–4 scale from least (0) to most (4) as well as access preloaded media content designed specifically for this trial. In order to access the media content, participants had first to enter a pain score. Nurses did not see the scores entered on the Navimed.The study lasted for 48 hours, after which time each participant completed a series of questions assessing her satisfaction with pain control and evaluating the Navimed. In the event, a patient was discharged before 48 hours; this assessment was performed just before the patient left the hospital. Participants were free to withdraw from the study at any time. Reasons for withdrawal or dropout from the study were recorded.Patients were initially approached at routine surgical preassessment appointments at the hospital, which they attended at least two weeks prior to booked gynaecological procedures such as a laparoscopic hysterectomy. Those meeting inclusion criteria were given an information leaflet regarding the study and the opportunity to speak with one of the doctors or nurses on the research team. A member of the research team obtained informed, written consent from patients prior to anaesthesia on the day of surgery. The study was performed over the period beginning from 13th November 2013 to 25th March 2014 inclusive.being female,age 18–90,elected patient,gynaecological surgical patients at UCLH,routine ward care postoperatively anticipated for at least 48 hours.The inclusion criteria includechronic pain diagnosis,intravenous drug users and other substance abusers,being unable to read or understand English (since device is programmed in English),being unable to give consent or lacking capacity.The main research questions were (1) whether patients used the Navimed device to record their pain in addition to regular pain monitoring by nurses and, (2) if they did, whether the pain scores on the Navimed differed significantly from those they reported to nurses. We were also interested in whether patients used the multimedia programmes loaded onto the device.The exclusion criteria includeTo calculate power, we used pilot data on 19 subjects of a previous study in which the mean frequency of nurse pain assessments in the 48 hours following surgery was 9.70 (SD 2.40), somewhat less than that required by hospital guidelines (12 4-hourly observations in the 48 hours following surgery). The minimum clinically important difference we wished to detect was a 50% increase in the frequency of observations to a mean of 14.60 using the Navimed. For this calculation, we assumed a standard deviation of 5 in both arms, a 5% noncompliance rate, and 1% dropout in the 48 hours following surgery. For 90% power and a two-tailed significance level of 5%, sample size required was 52.advice: about the nature of postoperative pain; about medication side effects; about how to use a PCA effectively,comedy: four audio tracks about London landmarks,film or TV: short nature films and cartoons,games: a jigsaw,guided relaxation: two spoken tracks (one progressive relaxation and one mindful breathing), designed for postoperative patients in the trial, and two music tracks with nature pictures,guided stretch: four videos of stretches done sitting on the bed, with spoken instructions, produced by a pain physiotherapist for the trial,information: about the acute pain team in the hospital, pain control options, and controlling side effects of drugs,music: Latin, blues, African, Brazilian, guitar, orchestra, and rock,talking books: four nonfiction stories.These options were selected from discussions within the acute pain team of the hospital on the basis of expert experience and best evidence as discussed in the introduction. The use of the Navimed device was automatically recorded on the device for each patient and subsequently downloaded and analysed by the research team.Patients randomised to use the Navimed were trained prior to their surgical procedure. The device has a touch screen and operates much like smartphones and tablets. Patients recorded a pain score, at rest and on movement, whenever they chose. They would do this by selecting a tab to rate their pain on the Navimed device and then by selecting a number between 0 and 4. After recording a pain score on the device, patients were presented with a number of options relating to further activities. These werePatients in both groups had the option to call for the nurse using the usual bedside call button at any time.The primary study objective was to assess whether patients used a handheld device to self-report pain over and above a normal baseline of nurse observations collected during usual clinical care.Secondary objectives were (1) to compare the device reported pain scores with the nurse-recorded pain scores (both 0–4), (2) to compare the pain scores between patients using the handheld device alongside standard care and those receiving standard care alone, and (3) to compare the qualitative and quantitative assessment of usefulness of the Navimed from the patients' perspective.http://dx.doi.org/10.1155/2016/9704185 for questions. They were also given the opportunity to write free text regarding their experience of postoperative pain management. Participants that used the Navimed were then asked further three closed questions and 7 numerical rating scales specifically about the device, with another free text space to feed back about potential improvements. All questions may be found in Supplementary Material.All participants were asked 20 questions about their postoperative experience: 17 using numerical rating scales and three closed questions regarding recollections: see Three people eligible to enter the trial declined to do so. The dropout rate after 48 hours, shown in t(50) = 2.75, p = 0.0080). This difference was accounted for by use of the Navimed since the number of nurse observations did not differ across the two groups (mean 22.62 (SD 8.20) and 23.27 (SD 7.23) (t(50) = 0.305, p > 0.05)); see Tables To assess whether patients used the handheld device to record pain scores in addition to standard nurse-collected pain observations, the total number of pain scores in each group was compared. The total number of pain scores was significantly higher in the Navimed than in the standard group (means 34.19 (SD 18.91) and 23.27 (SD 7.23), resp.,  t-test (t(50) = 4.07, p < 0.0010). Comparison between Groups S and D of the pain scores reported to nurses showed no significant difference over the 48-hour period  = 0.857, p > 0.050).Given the use of the Navimed, we tested for difference within Group D in mean pain scores reported on the Navimed and to nurses. Significantly greater pain was reported on the Navimed than to a nurse: means 1.02 (SD 0.87) and 0.28 (SD 0.29), respectively,t(50) = 1.94, p > 0.05). Both groups estimated spending about 30% of the time in severe pain. Least reported pain showed a floor effect, with a median score of 1.50/10 in both groups.The retrospectively rated worst pain reported was 5.80/10 (SD 2.70) in Group D with only one of the participants complaining of 10/10 severity and 7.20/10 (SD 2.60) in Group S with seven recalling 10/10 pain, but this difference was not statistically significant (t(50) = 0.83, p > 0.05), with breathing deeply/coughing  = 0.86, p > 0.05), with sleep  = 0.00, p > 0.05), and with getting out of bed  = 1.28, p > 0.05) did not differ between groups (see t(50) = 2.16, p = 0.036. For distress, the scores were Group D mean 3.30 (SD 3.20) and Group S mean 5.00 (SD 3.30), which was not statistically significant: t(50) = 1.82, p = 0.070.Pain interference with activities in bed, such as sitting up  = 0.52, p > 0.05) as were the number of patients who would have liked more pain relief  and the number who reported receiving information about options for pain treatment . Nor were there differences in the ratings of participation in decisions about pain treatment, satisfaction with pain treatment since surgery, with a mean just above 8/10 in both groups, and overall satisfaction with experience of pain control. For data, see Overall relief, rated as a percentage, from analgesics was similar across groups  = 1.36, p > 0.05), drowsiness  = 1.50, p > 0.05), or itchiness  = 0.35, p > 0.05), although patients with the device did retrospectively report significantly less dizziness  = 2.04, p = 0.047).There were no notable differences in extent of nausea  were satisfied with it and 20/26 (77%) found it very easy or easy to use. Patients used the full range of options available on the device; the three most commonly accessed functions were information, guided relaxation, and games see .The results from this pilot study demonstrate that patients made full use of the Navimed device and the majority found it helpful and easy to operate. This answers the primary objective of the study and confirms that further research is warranted regarding development of this concept. It is also reassuring to see that the presence of the Navimed device did not detract from normal level of attention from healthcare staff, with no significant difference between groups in the number of nursing pain observations.The significantly higher mean pain score recorded on the Navimed compared to scores reported to nurses was unexpected but is likely to reflect the fact that the nurse-recorded pain score involves a social interaction with both sides potentially able to influence the outcome ; for insThe secondary outcomes were exploratory and we did not power the trial to investigate them but to guide subsequent work. Most notable among these secondary outcomes is the apparent reduction in patient anxiety experienced in the device group, possibly associated with free access to information about pain, one of the most used functions, and with a sense of empowerment conferred by using self-initiated nonpharmacological methods to reduce pain distress. These ratings are subject to retrospective bias and imperfect recall compounded by a general anaesthetic and strong intravenous analgesics, but those considerations affect scores from both groups. Additionally, the retrospective report of pain is affected by a “peak end bias” whereby average pain rating over a given period is biased by the worst pain recalled and the pain at the end of the experience . These lIn a seminal publication, the Harvard economist Michael Porter describes better value in healthcare as improved outcomes with reduced costs , and patIn order to raise awareness and improve management, there have been recent suggestions that pain should be treated as “the fifth vital sign”  and evidThe supplementary material provided is the post trial questionnaire given to all participants at the conclusion of their involvement. It asks questions regarding the retrospective experience of pain as well other symptoms and emotions using both closed questions and numerical rating scales. Those participants that used the Navimed were then asked a further series of questions specifically regarding their usage of, and satisfaction with the device. The results from this questionnaire are included within the main text of the article.