F = 45%, age = 55.7 ± 18.7, 8–104) were searched after the patients had received a diagnosis of a neurological disease (new and old episodes) according to the nine classes of the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10). A set of consecutive statistical methods  were used to establish a link between MPV and neurological disease. A statistically significant (p < 0.05) relationship with MPV was found only in pain syndrome patients, with seven out of eight clinically diagnosed migraine episodes. With all other ICD-10 classes of neurological diseases, the effect of MPV was found to be nonsignificant (p > 0.05). MPV may implicate a clinical relationship with pain syndrome and migraine episodes. More complex statistics could help analyse data and find new correlations.Many studies have found correlations between abnormal MPV and clinical reactivity in a variety of diseases. In the present paper, we sought MPV-related neurological diseases that are less frequently reported in the literature. The electronic medical records of 852 neurological patients with mean platelet volume (MPV) measurements ( The mean platelet volume (MPV) is an easily measurable haematologic standard parameter. Many scientists have discussed its interpretation and have found correlations between abnormal MPV and clinical reactivity in a variety of diseases . It is bIn the present paper, we sought MPV-related neurological diseases that are less frequently reported in the literature. Some data suggest the role of changes in platelet functions among patients with migraine , particuIt was assumed that the effect of MPV on a neurological disease should be more explicit in some “nonspecific” clinical conditions, particularly those which cooccur with each other. If this relationship could be found, the identification of MPV-related diseases could be more feasible.F = 45%, aged = 55.7 ± 18.7, 8–104) were assessed after the diagnosis of a neurologic disease (new and old episodes) according to the ICD-10 at the Gorzów Wlkp. Multi-Specialist Hospital in the one and a half-year period from 1 January 2017 to 30 June 2018 .Altogether, 958 individual MPV measurements in 852 patients  analytical systems with EDTA-KE/2.7 mL samples.D) between objects  is defined as follows: D = |A‐B|/max, where the nominator is the modulus of A‐B and the denominator is the maximum of A and B. Before performing the distance calculation, the data were normalized into the 0–1 range. The resulting classification tree is presented in To determine a possible effect of MPV on the analysed neurologic diseases, taxonomic statistics were first assessed in the statistical analysis . InBy arranging the taxonomic heights (distances), it can be seen that until a certain order number, the heights are relatively similar to each other; above this number, the height rapidly increases see . Using sestimated breakpoint number = 799. The classification tree shown in It can be seen from the segmented regression in r linear coefficient. A pair of clusters was considered similar if the estimated p value of their correlation was <0.05.Then, to look for a closer similarity between the clusters, first, the percentages of patients in each ICD-10 disease class were correlated with each other using Pearson's Then, clusters were divided into “twin” = similar and “single” = dissimilar collections of patients following the fractions of the analysed diseases. To determine whether clusters were “twin” or “single,” patient cluster matching was performed using propensity score matching . In thisRoughly, p < 0.05) result for MPV was found only in 24 “single” patients  of the total 50 pain syndrome subjects, while in the remaining 26 “twin” pain syndrome patients , the effect of MPV was nonsignificant. The relative risk estimates for the analysed triplet together with other statistically significant selected biomarkers (red blood cells (RBCs), haematocrit, and haemoglobin) for “twin” and “single” clusters are reported in For the established “twin” and “single” clusters of patients, the effects of sex, age, and MPV on the number of disease cases were estimated using mixed effects Poisson regression . It is o10‐1)∗100% = 34% (one-third). However, in MPV-related patients, an opposite effect of RBC, haematocrit, and haemoglobin on the number of pain syndrome cases was observed, i.e., the higher the levels of biomarkers, the lower the chance of a pain syndrome.U) test was applied for the statistical analysis. Statistically significant (p < 0.05) and borderline statistically significant (p < 0.1) results are reported in Additionally, for identified “twin” and “single”  patients suffering from a pain syndrome, differences in other biomarkers , mean corpuscular haemoglobin concentration (MCHC), and C-reactive protein (CRP)) were tested between the types of clusters. Due to the nonnormal distribution of the biochemical indicators, a median .Finally, the specific disease was identified in the patients in the MPV-unrelated and MPV-related groups. Among all pain syndrome patients, eight were diagnosed with a clinical migraine, while the others were diagnosed with other headache syndromes. Surprisingly, seven of the migraine patients belonged to the MPV-related disease group, resulting in a statistically significant difference with the MPV-unrelated group with a Throughout the past decades, mean platelet volume, as a potential marker of platelet reactivity and a surrogate parameter for a broad variety of diseases, has been the subject of numerous investigations. To date, less attention has been paid to neurologic diseases in comparison to cardiovascular diseases , cancersRegarding neurologic diseases, we found three studies on fibromyalgia –30, whicA study conducted by Turkish authors  was simiGiven our results above, we suggest studying this kind of relationship using an alternative method, such as a taxonomical approach (by dividing the patients into clusters), and not by directly testing only simple independent groups. In our opinion, taxonomic approaches provide much more specific results and more evidence of the similarity and dissimilarity of patients, which could help lead to a hypothesis on MPV-related migraines.n = 50) and the final statistical inference based on the nearly 1% (8/852) of all analysed neurological episodes with diagnosed clinical migraines. It is difficult to obtain more precise statistical data, even though current epidemiological studies estimate the global prevalence of chronic migraine to be approximately 2% of the world population [However, a strong limitation of our results is the number of investigated pain syndrome cases (pulation . Moreovepulation . Therefopulation . Based oMPV may implicate a clinical relationship with pain syndromes and migraine episodesComplex taxonomic statistics and clustering data could help analyse data to find new correlations and provide another type of causalityWe believe that we have been able to determine a credible research pathway for the MPV biomarker assessment of the occurrence of pain syndromes and migrainesBased on the literature, the collected study material, and the statistical taxonomical analysis performed here, the following conclusions can be drawn:


To measure and compare musculoskeletal pain in patients with juvenile fibromyalgia (JFM) and polyarticular juvenile idiopathic arthritis (JIA), and to evaluate and compare pain perception and pain coping mechanisms in these patients. In this cross sectional study, we evaluated 150 children and adolescents, and their respective parents, from 3 different groups: JFM, polyarticular JIA, and healthy controls. Pain intensity and pain coping mechanisms were measured using specific questionnaires. Pain perception was evaluated according to three illustrations simulating situations that might cause pain: a shot, a bicycle fall, and social isolation. The patients’ parents also filled out the questionnaires and provided a pain score that matched their child’s perception of pain for each illustration. The highest pain scores, the lowest pain coping strategy scores, the highest pain perception scores for all three illustrations, and the worse health related to quality of life indicators were observed in the JFM group, when compared to the JIA and control groups. The same pattern was observed with their parents. Patients with JIA and JFM behave differently in relation to pain perception and the development pain coping mechanisms. Pain should be evaluated from different perspectives for an individualized and efficient treatment of patients. Musculoskeletal pain is one of the most common complaints from the pediatric age group. Many patients have idiopathic musculoskeletal pain (IMP), which does not necessarily have an apparent cause, is intermittent, and can be disabling, for a minimum period of three months.,,Some case series show that 25-40% of children and adolescents with chronic musculoskeletal pain syndrome meet the criteria for juvenile fibromyalgia (JFM).,,Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease characterized by arthritis that lasts at least six weeks in at least one joint. Pain is common in patients with JIA, especially in those with polyarticular impairment (five or more inflamed joints). Previous studies have shown that 86% of children with JIA present mild to moderate pain,,Pain, regardless of its cause, is perceived, tolerated and dealt with differently by patients. However, these aspects are rarely studied when JFM and JIA are analyzed.The present cross-sectional study was carried out in a specialized outpatient clinic of a tertiary hospital. One hundred patients aged 8 to 18 years old were included consecutively: 50 patients with JFM and 50 patients with polyarticular JIA. Patients with JFM met the criteria for fibromyalgia as established by the American College of Rheumatology in 1990.The control group consisted of 50 randomly selected children and adolescents, chosen in order of when they joined a leisure club. This group was paired off by gender and age, and they had no history of inflammatory disease or previous chronic musculoskeletal pain.Data was collected with regard to the age of onset, intensity, duration of the pain, and previous painful experiences that were related or unrelated to the disease  and use of analgesic and/or anti-inflammatory medication. For JIA patients, the disease activity and the number of active joints at the time of the interview were evaluated. We used the numerical visual analogue scale (VAS)Patients reported the intensity of their pain at the time of the interview and the average pain they felt during the previous week. The parents indicated the pain score that they believed their children felt on the day of the interview.To evaluate pain perception, we developed three vignettes related to situations associated with physical or psychological pain:physical pain related to a traumatic experience ;pain related to a medical procedure (shot); andemotional pain, due to social deprivation (excluded from a group of children).A designer drew up the vignettes after a consensus meeting among the researchers . The chaTo assess pain coping mechanisms, the Waldron/Varni Pediatric Pain Coping Inventory (PPCI) questionnaire, translated into Portuguese, was used.Patients with JIA were evaluated regarding the clinical activity of their disease according to the criteria from Wallace et al.Patients, controls and their respective parents signed consent forms. The study was approved by the Research Ethics Committee of the Universidade Federal de São Paulo (CEP-UNIFESP 0309/10).Initially, the data were analyzed descriptively. For the categorical variables, absolute and relative frequencies were calculated. For the numerical variables, summarized measurements were calculated . The means of the two groups were compared via Student’s t-test for independent samples. To perform an analysis for more than two groups, the means were compared using a variance analysis (ANOVA), followed by multiple comparisons  in order to pinpoint the differences. To verify the normality of the data, the Kolmogorov Smirnov test was used. In the case that there was no normality, the nonparametric Kruskal Wallis test was used, followed by the Mann Whitney test (if there was evidence of different means) with a Bonferroni correction. For the comparison of paired sample means, Student’s t-test was used. To verify associations between the categorical variables, the chi-square or Fisher’s exact tests were used if the samples were small. Linear associations between numerical variables  were analyzed using Spearman’s correlation. The internal consistency of the items that make up each of the five PPCI aspects was evaluated using Cronbach’s alpha. A significance level of 5% was used for all statistical tests.Three hundred interviews were performed with 150 patients and their parents. The clinical and demographic data of the patients and the demographic data of the controls are shown in Among the 50 patients with polyarticular JIA evaluated (seven had positive rheumatoid factor), the disease was active in 29 (58%) of them at the moment of the evaluation.Twenty-six patients with JFM (52%) and 11 patients with polyarticular JIA (22%) had severe pain (pain score > 8) in the week preceding the interview . Nine of the 50 patients in the JFM group (18%) had used painkillers in the week prior to the interview, while eight of the 50 patients with polyarticular JIA (16%) were on pain medication at the time of the interview. In the group of patients with JIA, we did not observe a statistical difference between the pain score on the day of the interview and the score from the week prior to the interview between the patients who were actively suffering from the disease (arthritis) and those who were not.There was a difference between the mean age of onset of pain in children in the JFM and JIA groups. The onset of pain began in JIA patients at a younger age  and their pain lasted longer  .We calculated the intraclass correlation coefficient between the pain scores provided by the children and adolescents of the JFM group and their parents. The value found was 0.716, with a 95% confidence interval (95% CI) ranging from 0.550 to 0.828. In patients with JIA, we found a value of 0.658, with the 95% CI ranging from 0.468 to 0.790.When analyzing each pain situation presented in the vignettes separately, the control group obtained higher scores than the patients with JIA in the social deprivation situation  and the pain related to a medical procedure situation .The Spearman correlation coefficient between the pain scores given by parents and by children after seeing the vignettes is presented in In the present unprecedented study, we evaluated and compared two aspects that are relevant for clinicians who follow up with children and adolescents with musculoskeletal pain: pain perception and pain coping mechanisms.Pain perception is the process by which an organism interprets and organizes sensations in order to give it meaning. Pain perception is not directly related to an active disease (the presence of arthritis or painful spots the body), but rather to a number of factors, such as the individual’s previous experience, social context, emotional state, gender, race, age and culture.The pain perception evaluation, which was performed through the presentation of simulated situations in the form of vignettes, showed that the JFM group had the highest scores (the highest pain perception) for the three situations presented, when compared to the other groups. The perception was greater for both the patients and their parents. The correlation between parents and children’s pain perception was low in all three groups. As such, the patients’ point of view should be considered.In the comparison of the three vignettes within the same group, we can see how previous lived situations can influence pain perception. Evaluating each group separately, we observed that, in the JFM group, the highest scores for pain perception were given in reference to the social deprivation simulation, a situation that these patients know well due to the limitations imposed by their pain.With the vignettes we were able to observe two aspects:the pain perception scores in the JFM group were much higher than in the other groups in all of the simulated situations;pain perception, when analyzing each individual group, is strongly influenced by the personal experience of each person.In the JIA group, the highest score obtained from the vignettes was for the social isolation simulation, followed by physical trauma and then, receiving a shot. All of the children and adolescents who made up the JIA group received shots regularly to inject medication, controlling disease activity, and for laboratorial exams. Because injecting medication may be a positive experience for these patients, it could have influenced the lower pain perception score. Similarly, the situations of isolation and physical restraint that are caused by JIA in certain moments may have influenced the higher score for the social deprivation vignette.The control group had the highest scores for pain perception from the shot simulation, followed by social deprivation and then, bicycle trauma. Healthy children and adolescents are not constantly subjected to experiences such as injectable medication. Many of these children were only given injections during their routine vaccination. We emphasize that this finding is unprecedented, since we did not find other articles aimed at measuring the perception of pain in hypothetical situations. The use of the vignettes designed in our study is still not well established in daily clinical practice. We believe that with the implementation of this instrument in the everyday routine of our outpatient clinic, we can obtain useful information to better design individual treatment plans.,The study by Varni et al.JIA, despite being an inflammatory disease, can structurally comprise the joints, tendons and muscles, making remission difficult. Illowite et al.It is commonly known that pain is a preponderant factor in patients with musculoskeletal pain that is associated with amplification, as in the case of FMJ. In our study, the JFM group had the highest pain scores when compared to the other groups. More than 50% of the members of the JFM group reported intense pain, with a pain score higher than 8 in the week prior to the interview. On the other hand, for the JIA group, this figure was lower (22%). This difference in the proportion of patients with intense pain between the groups confirmed our impressions formed in day-to-day practice: patients with JFM complain more of intense and persistent pain that interferes in daily activities in comparison to patients with JIA.Our data show that the parents of patients with JFM are able to measure the pain reported by their children better than the parents of patients with JIA. Pouchot et al.,Sawyer et al.Thastum et al.One of the limitations of our study is the fact that we evaluate subjective and personal data - pain - for which the gold standard is through self-reporting. Throughout the study we were careful to avoid external interference. All interviews were conducted by the same researcher (MMF), and the order in which the questionnaires were applied and vignettes were presented stayed the same for all the participants. The entire study was performed in the same physical space (the pediatric rheumatology clinic).Patients with JIA and JFM behave differently in relation to pain perception and the development of pain coping techniques. In our study, patients with JIA had experienced pain longer than patients with JRM, since the pain started earlier in the JIA group. This group developed a greater number of mechanisms for coping with pain. The more time exposed to pain could have contributed to the development of more coping skills.Pain originates from many factors and is influenced by several aspects while it lasts. We must evaluate the patient in pain from different perspectives. We have shown in our study that it is not enough to only measure pain intensity, we also need to deeply evaluate other aspects such as pain perception and pain coping mechanisms. Once each patient’s profile has been identified, it is the responsibility of all of the members of the multidisciplinary team to design an individualized therapeutic plan capable of relieving pain in its multiple form, with an emphasis on the physical, emotional, social and cognitive aspects.


This study evaluates whether patient education and individually self‐care reduces pain and improves QoL, mood and sleep during and after radiotherapy treatment for patients with head and neck cancer.A longitudinal, two‐armed feasibility study design was performed.Sixty‐four participants with curative intent were included in the study. All participants answered questions about pain three times a week and completed a survey questionnaire about pain, QoL, psychological aspects and barriers towards pain management at baseline, at 4 weeks and at 10 weeks. Thirty‐four of the participants attended in two education sessions on pain based on their beliefs about pain and received individualized self‐care instructions based on their weekly rating of pain.This study did not find any significant group differences for the pain, QoL, mood and sleep. It was not possible to include patients in the present study before the start of RT. The Swedish law restricts contact to patients before enrolment to the PRC. The patients were included within 2 weeks after receiving ongoing RT. The following inclusion criteria were used as follows: able to read, write and understand Swedish, registered in RT with curative intent and 18 years of age or older. In connection with scheduled RT, verbal and written information about the study was provided to all available patients by trained research nurses (TRN). After 1 week, the eligible patients were asked whether they wanted to be included in the study. Data in this study were collected as short message services (SMS) and at the PRC.2.32.3.1All participants answered a SMS with seven items on pain intensity and interference every Monday, Wednesday and Friday during the 10‐study weeks. If the SMS survey showed ≥3 numeric rating scales step increase on any items, a TRN phoned the patient the same day (no later than 3 days if a weekend). Based on the SMS scores, pharmacological treatment was promptly prescribed or adjusted. If the patient was displeased with the pain relief at the next day's phone contact with a TRN , the pharmacological treatment was adjusted. Both groups were offered care as usual at the PRC. Thus, they were encouraged to contact the TRNs by phone and had access to advice from the TRNs. The pharmacological treatment was based on identical principles for both groups and prescribed by the physicians according to the ward's policies Appendix .2.3.2The scientific literature , a TRN delivered a PowerPoint presentation covering the education areas. This presentation was labelled education session 1 (ES 1). To ensure that as many current needs as possible were addressed at week 4 (ES 2), the TRN initiated a structural discussion with the patient on the specific education areas presented at ES1. If needed, based on the second scoring of BQ‐II 1 week before the ES 2, additional education areas were presented at ES 2.The scientific literature of SC for patients with cancer was reviewed  Oral Cancer Pain Questionnaire  measures two targets: the subjective intensity of pain and how pain interferes with daily activities  assesses health outcome and perceived state of health Brooks, . The queThe EQ‐5D, a valid and reliable instrument  measures intensity of pain and pain interference (see description above)  assesses anxiety and depression  measures thoughts or feelings of catastrophizing in relation to how individuals experience pain  comprises 27 items on patient‐reported beliefs on pain and pain management , a self‐reported questionnaire, measures insomnia and provides a measure of the severity of sleep disorders , an alpha value of .05 and a power of 80%, each group was calculated to include approximately 30 patients.The sample size was assessed based on pain intensity . With an assumed clinically relevant average difference in four scale steps (Every second patient of eligible patients was assigned to the control group (30 patients), and every second patient was assigned to the intervention group (34 patients).2.6When patients agreed to participate in the study, their personal data were documented in consecutive order on a list in a confidential data file. All patients were assigned a code number and were consecutively distributed to the intervention group or to the control group – every other patient to the control group and every other to the intervention group.The first author generated the distribution sequence, registered participants and assigned participants to the intervention or control group.2.7p ≤ .05. The data are presented as median or mean values with standard deviation (SD) or minimum and maximum values and as percentages (%). The differences between groups at baseline were tested by the Student t tests for continuous variables and chi‐square test for dichotomous variables. For the primary outcomes, first the average score was calculated for three time points every week to measure the primary outcomes for 10 weeks. Then, a linear‐repeated‐measures multilevel model  was used to determine the effectiveness of the intervention compared with control conditions over time. The estimated impact . All tests were two‐tailed, and statistical significance was defined as a value of 3N = 55) did not meet the inclusion criteria (N = 16) or declined to participate (N = 39). The process of inclusion was ongoing between January 2015–December 2016.A total of 119 patients were eligible, and 64 were selected   (min 2–max 711) before inclusion in the study.SD 5.9 days) after the start of RT. Mean age of the participants was 65.1 years (SD 10.5 years), and the mean age of the non‐participants was 70.3 years (SD 12.8 years). Among the participants, 39 (60.9%) were men; the corresponding figure for the non‐participants was 31 (66.0%). The only reason reported for denying participating was poor health. Most participants cohabitated , most were former smokers , 10 (15.6%) were current smokers, and 26 (40.6%) had a university degree  and possibly constitutes an unintended bias related to denial to participate in the study by patients most affected by the HNC. One may argue that nurses are not trained in teaching patients, although in our study the intervention was structured, the TRNs were clinically experienced in the field of pain management for HNC patients and we can assume that our nursing staff was highly qualified. The interventions were manualized but treatment fidelity was not assessed, which might have influenced the accuracy of the delivered interventions . This applies to both the control and intervention groups (i.e. irrespective of patient education). A secondary effect of the study method probably encouraged the patient to pay attention to perceived symptoms and thus give the caregiver the opportunity to initiate adequate pain management in time. The study shows that it is not primarily pain education that the patient needs. Future research should include the identification of other needs that arise during the cancer treatment and how to optimize treatment for the patient's pain management and QoL.ASS and BL: Study conception and study design. ED, BL ASS and GL: Data analyses and manuscript drafting. All authors discussed the results, commented on the manuscript in different versions and approved the current version of the manuscript.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee.  and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all participants included in the study. Click here for additional data file. Click here for additional data file. Click here for additional data file.


The comprehensive treatment of pain is multidimodal, with pharmacotherapy playing a key role. An effective therapy for pain depends on the intensity and type of pain, the patients’ age, comorbidities, and appropriate choice of analgesic, its dose and route of administration. This review is aimed at presenting current knowledge on analgesics administered by transdermal and topical routes for physicians, nurses, pharmacists, and other health care professionals dealing with patients suffering from pain. Analgesics administered transdermally or topically act through different mechanisms. Opioids administered transdermally are absorbed into vessels located in subcutaneous tissue and, subsequently, are conveyed in the blood to opioid receptors localized in the central and peripheral nervous system. Non–steroidal anti–inflammatory drugs (NSAIDs) applied topically render analgesia mainly through a high concentration in the structures of the joint and a provision of local anti–inflammatory effects. Topically administered drugs such as lidocaine and capsaicin in patches, capsaicin in cream, EMLA cream, and creams containing antidepressants  act mainly locally in tissues through receptors and/or ion channels. Transdermal and topical routes offer some advantages over systemic analgesic administration. Analgesics administered topically have a much better profile for adverse effects as they relieve local pain with minimal systemic effects. The transdermal route apart from the above-mentioned advantages and provision of long period of analgesia may be more convenient, especially for patients who are unable to take drugs orally. Topically and transdermally administered opioids are characterised by a lower risk of addiction compared to oral and parenteral routes. Pain is defined as a subjective phenomenon that is associated with actual or potential damage to tissues. Typically, two components are found: sensory, associated with information of noxious stimuli, and emotional, which is associated with a patient reaction to painful stimuli that is often associated with psychological reactions and an individual sensitivity to pain. There are distinct types of pain regarding its time frame and pathophysiology. With respect to the former, pain may be divided into acute, which typically lasts up to three months, and chronic, which is present for a longer period of time. Regarding pathophysiology, pain may be divided into nociceptive , which is associated with damage of different internal organs, musculoskeletal system, soft tissues and the skin with intact nervous systems, and neuropathic pain, which is associated with damage or disease of the somatosensory nervous system, regardless of possible causes. It is common that mixed (both nociceptive and neuropathic) pain syndromes are present, for example in cancer patients with bone metastases.Patients diagnosed with chronic pain usually need a holistic approach to their numerous needs and typically require management that is comprised of pharmacotherapy, along with non–pharmacological measures. Regarding pharmacology, several groups of analgesics are available, and the general rule is to combine drugs with different modes of analgesic action, which allows for improved analgesia and reduced adverse effects. Typically, one or more drugs from three groups of analgesics are administered: non–opioids, opioid analgesics, and adjuvant analgesics. Apart from the antinociceptive efficacy and adverse effects profile, the route of analgesic administration plays a crucial role in achieving effective analgesia, as well as in minimizing adverse events.A drug administration route should be carefully selected while strongly taking into account the clinical status of patients, comorbidities, and age . An impoThe use of the transdermal route allows for the avoidance of problems associated with a disturbed absorption of a drug from the gastrointestinal (GI) tract or other GI problems , as well as the elimination of the first pass effect through the liver.Low concentrations of drugs and small fluctuations of their concentration in the blood serum guarantee long–lasting analgesia with a lower number of adverse effects, especially nausea, vomiting, and constipation.The transdermal form of drugs provides simplicity and convenience of administration, increases compliance, and improves patients’ quality of life.Benefits associated with the administration of opioid analgesics through a transdermal route are as follows:Features that should be fulfilled by a transdermal opioid are as follows: small molecular weight, high lipophilicity, high efficacy to compensate for limited absorption, low melting temperature, relatively short half–life, low daily dose, system dosing providing absorption from a relatively small area, and matrix patches in which a total amount of a drug is localized homogenously in an adhesion layer. The above technology ensures regulation of the release of an opioid based on a gradient concentration between a patch and the skin. The damage of a patch does not evoke an uncontrolled release of an active substance and enables the division of a patch into smaller parts in order to administer a lower dose of a drug, which is especially relevant in older patients. Natural features listed above ease the crossing of a drug through the skin and are possessed by two opioid analgesics: fentanyl and buprenorphine .The first drug used in the treatment of pain through the transdermal route was fentanyl. Patches of fentanyl release 12.5, 25, 50, 75, and 100 µg/h . A patchIn patients with fever and in those with excessive sweat, the absorption of the drug may be disturbed due to a layer of sweat separating the active surface of a patch from the skin. Patients with a patch may take a bath, shower, and swim, although they should not use solariums and saunas.After the fentanyl patch is first applied, the beginning of its analgesic action is delayed by up to approximately 12 h. Therefore, for this period of time, patients should be treated with other analgesics. In most patients, the fentanyl analgesic effects persist for 72 h (3 days) and, for this period of time, a patch should be administered. In some patients, a decrease of the analgesic effect is observed on the third day. In these patients, a change of patch every 48 h (2 days) may be considered. A fentanyl dose proportion to 90% undergoes biotransformation in the liver through the cytochrome P–450 enzyme CYP3A4, forming an inactive metabolite, norfentanyl. The rest of the drug (10%) is not metabolized. Fentanyl and its metabolite are excreted by the kidneys. The advantages of fentanyl are as follows: compared to morphine, it is less constipating, emetogenic, sedative, and does not release histamine; it is relatively safe in patients with renal failure.Fentanyl in patches is not recommended for the treatment of acute postoperative pain due to a slow onset of analgesic action after the first patch application. However, in postoperative analgesia, it is possible to use fentanyl administered by a transdermal route through a special micropump system (IONSYS), in which the acceleration of opioid absorption is achieved through an iontophoresis process. In this system, a small micro–pump with a diameter of an index finger is attached to the arm skin. After pushing a special button, a dose of fentanyl equaling 40 µg is applied. For safety reasons, the device possesses a programmed 10–minute refraction period when administration of the drug is impossible. The number of possible doses administered per day (24 h) is 80. In patients treated with fentanyl pumps, a constant monitoring of the respiratory system function is required. Fentanyl products administered by transmucosal routes  are recommended for the management of breakthrough (episodic) pain .Buprenorphine is available in patches releasing 35, 52.5, and 70 µg/h. The maximum recommended dose of buprenorphine in Europe is 140 µg/h. In older patients, a starting dose may equal 8.75 µg/h or, more frequently, 17.5 µg/h . A change in the dose should take place after at least two consecutive applications of a patch. The pharmacokinetic steady–state and an equilibrium drug distribution between blood and cerebrospinal fluid are reached after at least five plasma half–lives. Rules of patch applications are the same as that for fentanyl. To decrease the risk of dermatitis induced by a buprenorphine patch, some clinicians recommend keeping the patch in the air to evaporate gaseous substances contained in a patch before putting the patch on the skin; this is recommended only for an original buprenorphine product. Original buprenorphine patches are normally changed every 3.5 or 4 days. Dosing twice a week is more convenient for many patients because of fixed days for patch changes. A generic product is normally changed every three days. In Europe, a seven–day buprenorphine patch is available releasing 5, 10, and 20 µg/h .Buprenorphine has been used in clinical practice for over 30 years, but the interest in the drug increased after introducing transdermal products. Buprenorphine is a semi–synthetic derivative of thebaine. The buprenorphine molecule contains a basic skeleton of morphine, but there are significant differences between their structures. It may be predicted that buprenorphine displays some unique and distinguished pharmacological and clinical features while preserving general morphine properties.Buprenorphine strongly binds to opioid receptors, displaying the highest affinity compared to other commonly used opioids. Buprenorphine binds to opioid receptors more slowly and dissociates more slowly than fentanyl, which is associated with less risk of developing opioid withdrawal. Despite the fact that buprenorphine in therapeutic doses displays a high affinity with opioid receptors, its degree of binding with opioid receptors is small (less than 50%). This leaves a significant percentage of opioid receptors free, making it possible to use buprenorphine concurrently with other opioids. However, concurrent treatment with other opioids renders only additive effects. Buprenorphine is a partial agonist of μ opioid receptors. Therefore, a curve dose/response is not a simple line but an “S” shape. In the range of therapeutic doses, the curve is linear for doses below 7 mg/day, i.e., each dose increment induces an improvement in analgesia. This means that, in this dose range, the drug acts as a pure opioid agonist. A ceiling effect of analgesia is achieved when daily doses exceed 16 mg, which are not used in the clinical practice of pain management. A potentially important, although not fully recognized, role of buprenorphine is the interaction with orphanin receptors, ORL–1. This receptor is similar to opioid receptors and binds nociceptin, which, after the activation of these receptors, antagonizes the analgesic effects of opioids.After absorption from a transdermal patch, buprenorphine binds to blood proteins in circulation to a large extent (96%). This may affect its pharmacokinetics and action, especially in patients with cachexia. In the liver, the drug is metabolized through the cytochrome P–450 enzyme CYP3A4 to become an active metabolite, norbuprenorphine. A third of the dose administered by a transdermal route is excreted via the kidneys and two–thirds of the drug is excreted with the stool. Transdermal buprenorphine is recommended for cancer and non–cancer patients with moderate to severe pain intensity of musculoskeletal, neuropathic, and visceral pain. Apart from pain management, buprenorphine is used in substitution therapy for patients diagnosed with drug addiction. For this indication, its effectiveness is comparable with methadone.Drug concentrations in the blood serum that can render analgesia are achieved within 12–24 h after a first patch application, which accounts for the fact that buprenorphine is similar to transdermal fentanyl and should not be used in the treatment of patients with acute and breakthrough (episodic) pain. Transdermal buprenorphine renders a stable concentration of the drug in the blood serum, similar to transdermal fentanyl. It was demonstrated that the profile of adverse effects of transdermal buprenorphine is similar to other opioids. Long–term treatment with the drug is characterized by a low frequency of constipation and CNS adverse effects, such as nausea, vertigo, and weakness. The low frequency of adverse effects on the CNS might be due to the antagonist action of buprenorphine on the kappa opioid receptor (KOR). The low frequency of adverse effects in the GI tract is probably associated with a high lipophilicity of the drug. The safety profile of buprenorphine is better compared to other opioids.Buprenorphine displays less neurotoxic effects compared to other opioids (such as fentanyl), especially in older patients and those with dementia. Clinical studies have demonstrated that buprenorphine dose increments allowed the achievement of good analgesia with a limited risk of respiratory depression. This differentiates buprenorphine from other “strong” opioids that display dose dependent respiratory depressant effects. There is evidence from animal studies that most opioids (apart from buprenorphine and oxycodone) induce some degree of suppression of the immune system through modification of NK  cells function, lymphocytes T, action of interleukin–2, or interferon gamma. Lack of negative impact on the immune system may improve safety of the drug regarding infections and cancer dissemination. Moreover, a significant advantage of buprenorphine, which is similar to fentanyl, is high safety in using the drug in patients with renal failure .Tolerance development for analgesia during treatment with transdermal buprenorphine was explored in comparative studies with transdermal fentanyl. The increase in demand for fentanyl was at 2% per day and at 0.1% per day for buprenorphine, which is a result of the broader mode of action of buprenorphine on opioid receptors. Because of the strong analgesic potency of transdermal buprenorphine and the low frequency of tolerance development for analgesia, high doses of the drug in clinical practice are rarely required. The most frequently used dose range is 35–70 µg/h.Opioids induce analgesia by binding to opioid receptors in the CNS . Opioid receptors have also been shown to be present on peripheral sensory nerve terminals in inflamed tissues. Clinical studies have demonstrated analgesic efficacy when opioids are applied topically in certain situations such as skin ulcers and oral mucositis. The advantage of administering an opioid topically is the avoidance of systemic adverse effects such as nausea, constipation, and sedation.Morphine may also be administered through the mucosa. A 0.1–0.2% morphine–water solution may be used topically in the treatment of pain associated with changes at the oral mucosa evoked by radiotherapy and chemotherapy . A 0.1% morphine gel is applied on skin ulcerations, skin damage induced by radiotherapy, and pressure sores . Before All joint structures, apart from cartilage, are very rich in nerves. Thus, pain in joints and bones are usually of severe intensity. Prostaglandins play a main role in the process of inducing peripheral inflammatory pain; therefore, NSAIDs, which have a basic mechanism of action of blocking prostaglandin formation, are an important component in the treatment of this type of pain. The concentration of an NSAID in the blood serum determines its analgesic effects, and its concentration in a joint decides its anti–inflammatory effect.NSAIDs administered systemically achieve a high concentration in the blood serum and may induce adverse effects in the circulatory system, GI tract, kidneys, and liver . In contNumerous studies have proven that, after local NSAID administration on the skin, the concentration of a drug in the blood serum reaches only 5–15% of the concentration achieved after systemic administration, whereas some parts of a drug penetrates to the synovial fluid and synovial membrane. Penetration of drugs may be significantly improved through the use of ultrasound and iontophoresis. Concentration of NSAIDs after topical administration in the joint cartilage and in the meniscus is 4–7 times higher compared to that after an oral administration of NSAID; in tendinous cots and in the bursa, it is a few dozen times higher compared to that after an oral administration of NSAID. The NNT (the number needed to treat) for topically administered NSAIDs is 3.9 for acute pain syndromes and 3.1 for chronic pain. In chronic pain with an accompanying inflammatory process, combining a local and orally administered NSAID seems to be a good approach .2, in a single dose of 30–50 g. A gram of cream contains 25 mg lidocaine and 25 mg prilocaine.EMLA cream is an oil–water lotion containing lidocaine and prilocaine in a 1:1 ratio. It is a unique local anesthetic formulation, which, thanks to its large water content, is easily absorbed through the skin. In addition, due to the fact that the active substance is present in the form of more active alkaline compounds contained in small lipid drops suspended in water and not in a ionized salt form, it is possible to obtain an effective skin anesthesia up to approximately 0.5 cm in depth. This product is a eutectic mixture, which means that the composition of the drug is matched in a way that the melting point of the mixture of both components is different than the melting points of the individual components. In the temperature of human skin, this product preserves a liquid form, thanks to which it has a chance of being absorbed through the skin and inducing its anesthesia. According to the literature, this product may be applied on quite a large skin surface, even over 400 cmIndications for EMLA cream administration include the following: skin anesthesia alleviating acute pain in surgery, limited to small depth of the skin  and localized peripheral neuropathic pain, for example postherpetic neuralgia (PHN), especially in young patients with contraindications to sympathetic system blocks. When using EMLA cream on a large surface, it is necessary to monitor circulatory system function, lidocaine, prilocaine, and methemoglobin concentrations.Distinguished from EMLA cream, patches containing 5% lidocaine act mainly locally through a pathology-dependent form voltage sodium channels  formed in an injured nerve. VGSC gather in places of nerve injury, initiating repetitive ectopic excitations. These channels mark a high ability of lidocaine binding and a slow dissociation. Lidocaine released from a patch penetrates through the skin and, to a negligible degree, is absorbed into vessels; therefore, it does not induce circulatory complications and there is no need to monitor circulatory system function. Lidocaine contained in a patch binds with internal wall VGSC, which are formed in nerve endings and keratinocytes. As a result of blocking VGSC, ectopic excitations are inhibited, but there is no blocking of afferent nerve conduction .The second mechanism of lidocaine is associated with an inhibition of the release of nociception process mediators by keratinocytes. Keratinocytes participate in a system of signal transfer, and their activation induces sensitization and depolarization of primary sensory nerve endings through purinergic receptors (P2X) and an increase in expression of neurokinin receptor NK1 activated by substance P release, which leads to the activation of primary nociceptive sensory nerve endings. Lidocaine in patches additionally induces an effect of skin cooling (hydrogel bandage) and provides mechanical protection of skin areas involved in the disease process.Patches are applied on the skin in painful places once a day and left for 12 h.There should also be a break lasting 12 h, as a break in patch application minimizes the risk of local skin reactions.With one application, a maximum of three patches is allowed.The most frequent adverse effect of 5% lidocaine is a local skin irritation .Recommendations for the use of 5% lidocaine include the following: as a first line drug in the treatment of localized, peripheral neuropathic pain , alone or in combination with another first line drug and for central pain induced by spinal cord compression caused by a metastatic tumor to the subarachnoid space. The NNT for lidocaine in PHN is 4.4 and NNH (the number needed to harm) is approximately 28. The use of 5% lidocaine is effective in the following pain conditions: postherpetic neuralgia, painful diabetic neuropathy; its effectiveness is comparable to amitriptyline, capsaicin, gabapentin, and pregabalin, intercostal neuralgia, persistent postoperative pain , meralgia paraesthetica, low back pain and muscle–fascial pain. The rules of patch application and adverse effects are as follows:The drug displays good absorption from the mucosal surface and, through this, provides the possibility of superficial anesthesia. In chronic pain treatment, it is used, for example, in pain syndromes localized in the pelvis in women .Capsaicin is a highly selective agonist of the vanilloid receptor from a group of transient receptors of potential TRPV1 . Initially, capsaicin activates nociceptors in the skin, which evokes irritation and erythema induced by a release of vasoactive neuropeptides (substance P). After exposure to capsaicin, nociceptors in the skin are less sensitive to different stimuli; therefore, the late action of capsaicin is depicted as anesthesia.After one week from the patch application containing capsaicin with a high (8%) concentration, the channels for calcium ions for the skin open, leading to the sharp influx of calcium to cells and subsequent reversible damage of mitochondria. This consequently induces long-term atrophy of peripheral skin nerves. Capsaicin–induced changes in nociceptors of the skin and in peripheral nerves are reversible. A return to the normal function of receptors and repair of nerve fibers are observed after 12 weeks. This mechanism of action of capsaicin patches with a high concentration should be classified as a neuro–destructive action .The mechanism of action of capsaicin is also based on the elimination of the neurotransmitter substance P from nerve fibre endings. As a consequence, there is a reversible decrease in stocks of substance P and a decrease of pain transmission from peripheral nerve fibres to the CNS . Capsaic2) and contains 179 mg of capsaicin (640 µg capsaicin/cm2). A maximum of four patches are recommended. A patient must be informed that reactions, such as pain or burning, erythema, itch, and edema, may appear in the area where the patch is applied [Transient burning pain, erythema, and itch in the area of patch application.Adverse reactions are transient, self–limiting, and usually of mild or moderate intensity.No neurologic function limitations were found, apart from periodic disturbed hot sensation in the area of patch application.High price of the drug.The lengthy time duration of a procedure (approximately 3 h).In clinical studies, a patch with 8% capsaicin demonstrated high efficacy in patients with postherpetic neuralgia (PHN) and neuropathy during the course of HIV, as well as in the treatment of neuropathy after chemotherapy. Studies are ongoing on the use of patches containing 8% capsaicin in patients with diabetic neuropathy; the high efficacy of capsaicin ointments with low concentration for this disease might suggest that a high concentration of capsaicin should be equally or more effective. A patch with capsaicin has dimensions of 14 × 20 cm (280 cm applied . The advN–methyl–d–aspartate) receptors, adenosine receptors, and sodium channels. The latter mechanism of action  might be a theoretical base for the beneficial action of this group of drugs in peripheral neuropathic pain, administered locally in the form of ointments or creams. Clinical studies demonstrate the efficacy of tricyclic antidepressants, especially doxepin and amitriptyline, in the treatment of peripheral neuropathic pain. Indications for a local administration of tricyclic antidepressants are the following pain syndromes: carpal tunnel syndrome, neuralgia of intercostal nerves, postherpetic neuralgia, complex regional pain syndrome, painful diabetic neuropathy, meralgia paraesthetica, coccydynia, costochondritis, mucositis after chemotherapy and intractable itch that accompanies, for example, atopic dermatitis.The predominant mode of action of tricyclic antidepressants that are used in the treatment of neuropathic pain is the activation of descending pain inhibition through inhibition of the reuptake of serotonin and noradrenaline from the synaptic cleft. An additional consequence of this is potentiating opioid analgesia. Other tricyclic antidepressant modes of action comprise a blockade of NMDA  is 5% doxepin hydrochloride. The drug should be contained in temperatures below 27 °C. It should be applied as a thin layer on the skin surface, not exceeding 10%, three to four times a day, with a break of at least 3 to 4 h between applications. It is not recommended to use the cream under an occlusive bandage due to the risk of excessive absorption into the circulation. The recommended period of therapy in the case of an itch is eight days; in the treatment of peripheral neuropathic pain, treatment time is prolonged to four weeks. After application of the drug on the skin, hands should be accurately washed and contact of the drug with mucosa and the conjunctiva of the eye should be avoided.The most frequent adverse effects are comprised of burning, tingling, or feeling a stinging sensation in the area of application. Other adverse effects induced by excessive absorption of the drug into the circulation are as follows: drowsiness, dizziness and headache, dry mouth, dry conjunctiva in eyes, blurred vision, and taste change. Very rarely, GI symptoms were reported such as nausea, vomiting, dyspepsia, diarrhea, or constipation. There were also symptoms such as ringing in ears, agitation, disorientation, urine retention, cardiac arrhythmia, changes in blood glucose levels, and fever. Caution is recommended when administering the drug in patients diagnosed with glaucoma, prostate hypertrophy, depression, severe heart, and liver disease. The drug is not recommended in children under the age of 12. No studies were conducted on the safety of the drug in pregnancy and during breast feeding. The most frequent adverse effects, which do not require treatment cessation, are discomfort  in the region where the drug is applied on the skin. Drowsiness suggests the systemic absorption of doxepin . More stIn a rat model of neuropathic pain, amitriptyline (ointment) administered locally on the injured paw effectively decreased pain intensity. This analgesic effect was reversed by systemic administration of caffeine, which is an antagonist of the adenosine receptor. It is suggested that at least part of the peripheral analgesic effect of amitriptyline is associated with peripheral adenosine receptors. The application of amitriptyline on the skin of a healthy patient did not induce an analgesic effect, which suggests that, in this case, a local action of the drug was predominant. There is slight evidence of the efficacy of tricyclic antidepressants in humans. Studies refer to a small number of patients, many of which have a relatively short follow-up period. This hinders the interpretation of the results.Nitrates are mainly used in the treatment of ischemic heart disease. However, drugs forming this group also display analgesic and anti–inflammatory effects. It is known that exogenous nitrates stimulate the release of nitrogen oxide (NO) from endothelium cells. This substance is a very strong mediator in many systems, especially in the central and peripheral nervous systems. It seems that NO exerts its action through the stimulation of an increase in the concentration of guanylyl cyclase, increasing the level of cGMP. NO may also activate sensitivity to ATP potassium channels and, in this way, activate pain relief in the periphery. It was demonstrated that ointments or patches containing glycerol trinitrate (nitroglycerine) display analgesic efficacy in the following conditions: rheumatoid arthritis, ankylosing spondylitis, costochondritis, muscle–fascial pain, complex regional pain syndrome, bursitis, coccydynia, bone metastases, vulvodynia and venous leg ulcers.There is data indicating that the local action of nitrates potentiates analgesic effects of “strong” opioids, which indicates that this effect is a result of nitrate absorption and because of their central mode of action. The use of nitrates may be especially useful in patients in whom, due to renal, liver, heart, and GI tract diseases, NSAIDs are contraindicated. The main adverse effect associated with a local application of nitrates is frequent headaches .Clonidine administered in transdermal patches effectively eases pain in the following diseases: migraine, face pain and complex regional pain syndrome. This route of clonidine administration is associated with typical systemic adverse effects such as hypotension, sedation, and dry mouth. This is typical for systemic administration. Topical administration of clonidine effectively reduces pain intensity in painful diabetic polyneuropathy, postherpetic neuralgia and hyperaesthesia of the skin in trigeminal neuralgia .The analgesic effect is probably a result of the absorption of the drug, and it is associated with a presynaptic decrease of noradrenaline release from endings of the sympathetic nervous system and with an increase in the release of endogenous opioids  .Cannabinoids administered locally may induce analgesia through actions on cannabinoid receptors, CB1 and CB2 . ActionsThere has been a continuous increase in knowledge and understanding of the pathophysiology of pain and its treatment. There are several routes of analgesic administration: oral, sublingual, buccal, intranasal, inhaled, subcutaneous, intravenous, intramuscular, rectal, intramedullary, intrathecal, transdermal and topical. Although most patients suffering from pain are treated with analgesics administered by oral and parenteral routes, there is increasing scientific evidence based on well-documented clinical studies that locally administered drugs may be at least as effective as those administered by the oral route . An advaIt should be remembered that simple methods of pain treatment are available through the topical administration of some drugs . Through


Pain, a symptom often present in patients with Chronic Obstructive Pulmonary Disease (COPD), alters quality of life. COPD exacerbation augments several mechanisms that may cause pain  and therefore we hypothesized that pain might be increased during exacerbation.A prospective cohort study was conducted in patients admitted for acute exacerbations of COPD (AECOPD) in two emergency departments in France and Canada. Patients with cancer-related pain or recent trauma were not included. The Short Form McGill Pain Questionnaire (SF-MPQ) and the Brief Pain Inventory (BPI) scale were used to evaluate pain intensity and location. Patients also completed the Borg Dyspnea Scale and Hospital Anxiety and Depression Scale. The questionnaires were completed again during an outpatient assessment in the stable phase. The primary outcome was difference in pain intensity (SF-MPQ) between the exacerbation and stable phases.Fifty patients were included. During exacerbation, 46 patients (92%) reported pain compared to 29 (58%) in the stable phase (p<0.001). Pain intensity was higher during exacerbation . Pain was predominantly located in the chest during exacerbation and in the limbs during the stable phase. Pain intensity during exacerbation correlated with anxiety score.The frequency and intensity of pain were higher during AECOPD, with a specific distribution. Pain should therefore be routinely assessed and treated in patients with AECOPD. The current aim of treatment for exacerbations of chronic obstructive pulmonary disease (COPD) is to relieve the respiratory symptoms, improve respiratory function and normalize blood gases . COPD isPain is a frequently reported symptom in patients with COPD, even in non-palliative stages of the disease –8. TwentWe hypothesized that since the factors that have been associated with increased pain, as listed above, worsen during exacerbations, this could also lead to increased pain intensity and/or the number of pain-sites. A better understanding of pain during COPD exacerbations could improve its management. Effective analgesia would also facilitate patient compliance with AECOPD treatments and early rehabilitation ,14.The primary aim of this study therefore was to compare patient-reported COPD pain intensity during the stable phase and during exacerbation. The secondary aims were to determine if the location of pain changed between the stable and exacerbation phases and to screen for associations between pain intensity and symptoms of dyspnea, anxiety/depression, GOLD stage, exacerbation severity, and the need for noninvasive or invasive ventilation and/or the necessity for intensive care unit admission.This prospective cohort study was conducted in two university hospitals . The protocol  was approved by the ethics committees of both institutions . All information regarding procedures and data privacy were made known to the participants before obtaining signed consent. Patients were included if they were admitted for an AECOPD while still in the emergency department. Exacerbation was defined, according to the recommendations of the Global Obstructive Lung Disease Initiative (GOLD), as an acute event characterized by a deterioration of respiratory symptoms that was greater than usual daily variations and which required an adjustment of treatment )Pain intensity (SF-MPQ) was significantly correlated with Borg scale scores , anxiety  and depression symptoms (HADS)  during exacerbation. During the stable phase, pain intensity was only correlated with Borg scale scores . In multiple regression analysis, only correlation between pain intensity (SFMPQ) and anxiety remained significant during exacerbation (p<0.001), and between pain intensity (SFMPQ) and Borg scale scores at stable phase (p = 0.01). In univariate analysis showed pain intensity tended to be higher in patients with stage IV COPD both during exacerbation (p = 0.06) and in the stable phase (p = 0.15). Pain intensity was higher in patients with lower BAP-65 scores  but did not differ between patients who required standard care and those who received ventilation or intensive care Click here for additional data file.S1 TableThe dataset includes: participant characteristics and history; exacerbations characteristics; questionnaire results at inclusion and during the stable phase.(CSV)Click here for additional data file.


In patients with loin pain hematuria syndrome (LPHS), a response to percutaneous renal hilar blockade (RHB) and a multidisciplinary team (MDT) evaluation predicts patient’s potential renal auto-transplantation (RAT) success.A pain assessment was performed using a 0–10 numeric pain rating scale prior to a percutaneous RHB under CT guidance. If the pain score was reduced > 50% immediately after the RHB, patients were evaluated for RAT by a MDT. Pre-operative and 1-year post-operative quality-of-life surveys were administered to each RAT patient.43 LPHS patients were referred for RHB. Of the 38 patients who received a RHB, 31 had > 50% reduction in pain scores. Pre- and post-RHB mean pain scores were 6/10 and 0.7/10, respectively, in patients who had > 50% reduction in pain. 22 of the patients who responded favorably then proceeded to RAT. Twelve patients had at least 1-year follow-up after RAT. All patients had a meaningful decrease in their pain. Mean pain score at 1 year was 0.8/10 for an 85% overall reduction in pain. 92% of patients experienced a ≥ 50% reduction in pain at 1 year. Mean Beck Depression Inventory (BDI) score (0–66) 1 year after RAT decreased from 25.2 pre-op (moderate depression) to 12.8 post-op .A MDT approach utilizing a RHB should be considered as a tool to select appropriate LPHS patients for RAT to achieve long-term success in reducing chronic pain and depression while increasing quality of life. Loin pain hematuria syndrome (LPHS) was first described in 1967 as severe unilateral or bilateral flank pain with gross or microscopic hematuria . While mTherapies to treat the chronic pain are percutaneous regional nerve block, surgical sympathectomy, renal capsulotomy, vascular pedicle denervation, ureterolysis, nephrectomy, and renal autotransplantation (RAT) . The evoOne reason for failure of this therapy is the difficultly of establishing the correct diagnosis . We propWe defined LPHS as chronic, unbearable flank pain with or without hematuria in the absence of an infection, nephrolithiasis, or upper tract obstruction. A multidisciplinary team (MDT) was created consisting of an urologist, interventional radiologist, and transplant surgeon to evaluate and treat LPHS. The protocol started with all referrals filtered through our senior urologist to rule out pathology or other causes of pain. After a diagnosis of LPHS was established, all patients were then referred to interventional radiology for a RHB.The interventional radiologist evaluated patient pain at the time of the procedure. Blocks were performed using the same protocol. Pain was graded by the patient on a Visual Analog Scale (VAS) from 0 to 10 where 10 is worst pain and 0 is no pain. Patients were positioned prone on a CT table. The renal artery was identified by non-contrast CT , and the Medical Outcomes Study Questionnaire Form 36 Health Survey (SF-36) before and after RAT . The intBetween 2013 and 2017, 43 new patient encounters were recorded for LPHS in our institution’s urology clinic, and a RHB was recommended in all cases. 38 patients ultimately underwent RHB . Mean patient age was 35.8 years. 66% of the patients were female. 63% of the blocks were performed on the right. No major complications were encountered from the hilar block. However, bleeding is the main concern for possible complication. Infection does not appear to be a risk, and antibiotics are not given for the procedure. One patient had a horseshoe kidney, and two renal arteries were targeted; a block was performed at each location. In one patient, the genitofemoral nerve was also affected by the block causing transitory inguinal pain.Of the 38 patients who received a RHB, 82% of them had > 50% reduction in pain. Pre-RHB mean pain score was 6.0 ± 2.0 with post-RHB pain score being 1.1 ± 1.5. Mean duration of chronic pain prior to RAT was 3.6 ± 7.6 years. Mean pain reduction was 78% for all RHBs. Among those patients who had a < 50% reduction in pain from the RHB, there was a reduction in pain from a mean of 5.1 down to 3.0 accounting for a mean pain decrease of only 34%. Twenty-two (71%) of the patients who responded to the RHB then proceeded to RAT. Nine (29%) patients did not proceed to RAT: one was denied by insurance, four chose alternative therapies , two were not appropriate surgical candidates , and two were lost to follow-up. All patients who underwent a RAT had a successful surgery defined by graft function which remains at 100% for all patients. All surgeries were started laparoscopically but two had to be converted to open. Mean operative time was 4 h 58 min. 29% patients had been diagnosed with depression. 74% were taking chronic pain medications. Pain was described as burning by 8 (35%), aching by 17 (74%), stabbing by 21 (91%), and dull by 15 (65%).Of the 22 patients who received RAT, 55% patients have at least 1-year follow-up after surgery. One-year pain assessment was 0.8 ± 1.2 with an overall pain decrease of 85%. All 12 patients had a sustained improvement in their pain, while 92% had a 50% or greater improvement. Mean BDI score (0–66) 1 year after RAT decreased from 25.2 pre-op (moderate depression) to 12.8 post-op . There were significant shifts in quality of life and pain affecting quality of life .In the literature, the success rate of RAT is unacceptably low given the magnitude of the operation , 10. UsiOne hypothesis our group entertained is if RHB could be used as a bridge to surgery, similar to joint injections prior to arthroplasty. Adding triamcinolone to the injection was tested in five patients. No patients described sustained reduction in their pain beyond the half-life of the bupivacaine; so the steroid addition was discontinued. RHB is a one-time treatment for diagnosis only. Our theory is that any insult to the kidney can create ongoing pain. Furthermore, the block only lasts between 12 and 48 h. A limitation of this study is the small number of patients with a 1-year follow-up. Unfortunately, we do not have enough patients at time of the manuscript creation to power any statistics beyond what is presented. While our 1-year experience is encouraging, we will continue to follow these patients for 5- and 10-year outcomes which are not available at this time.In conclusion, RAT should be considered in the appropriate population after other disease processes have been ruled out by a MDT. RHB is a tool for the team to define LPHS patient’s appropriateness for RAT. This study confirms that when this protocol is used, RAT can achieve a dramatic reduction in long-term pain allowing for a significant reduction in chronic depression and increase in quality of life.


The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data.This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed.p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase . No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event.Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase.NCT01931475. Registered 29 August 2013.ClinicalTrials.gov identification number  Osteoarthritis (OA) is a common degenerative joint disorder and its prevalence increases with age . It is eAlthough OA pain has traditionally been considered as peripheral/nociceptive pain that results from inflammation or mechanical damage in peripheral tissues, emerging evidence suggests that central sensitization is also an important mechanism underlying OA pain , 13. CenA double-blind, placebo-controlled, 13-week study of duloxetine treatment in Chinese patients with OA pain was recently completed. Results from this 13-week placebo-controlled study showed a significant improvement in both the primary outcome measure of pain severity and in most of the secondary outcome measures . PatientThis was the 13-week, open-label, extension phase of a randomized, double-blind, multicenter, placebo-controlled trial  . PatientThis extension phase study was conducted in accordance with consensus ethics principles derived from international ethics guidelines, International Conference on Harmonisation Guideline for Good Clinical Practice E6, and all applicable laws and regulations.Eligibility criteria have been described previously . The maiPatients were excluded from the trial if they were taking any excluded medications .Both the participants and investigators remained blinded to original treatment allocation when the patients entered into the extension phase. Concomitant use of analgesics and other medications was not restricted in the extension phase (except for the few which may pose drug-drug interaction risks) and depended on investigators’ judgment. However, no rescue medication  was allowed during the 24 h prior to any study visit during the extension phase.The BPI–Severity and BPI–Interference scales were completed by the patient at each study visit to measure the severity of pain and the interference of pain on function during the previous 24 h before the scheduled visit. The average pain item of BPI-Severity was assessed as the primary efficacy measure. Other BPI–Severity items include worst pain, least pain, and pain right now. The BPI–Interference items include general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Ratings of the BPI items range from 0 (no pain/does not interfere) to 10 (pain as severe as one can imagine/completely interferes) .Safety measures assessed during the extension phase included treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), the Columbia-Suicide Severity Rating Scale, assessment of falls using solicited questioning, standard laboratory assessments, vital signs, and discontinuation rates due to adverse events (AEs).All analyses were conducted on an intent-to-treat basis. Statistical comparison between treatment groups was not performed for the extension phase. Within-group changes from baseline to endpoint were evaluated by two-sided t-test for efficacy measures and the Wilcoxon signed-rank test for safety measures. Unless otherwise stated, baseline and endpoint were defined as the last non-missing observation during the placebo-controlled phase and the last non-missing observation during the extension phase (last observation carried forward), respectively . ChangesPatients who took duloxetine and reported a ≥30% reduction in BPI average pain during the placebo-controlled-phase were defined as placebo-controlled phase duloxetine responders. The maintenance of effect of duloxetine 60 mg QD during the extension phase was evaluated in placebo-controlled-phase duloxetine responders by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase. At the significance level of 0.025 (one-tailed), the null hypothesis of non-maintenance was rejected, if the upper limit of the 1-sided 97.5% CI was a ≤1.5 point (non-inferiority margin) increase in BPI average pain. A non-inferiority margin of 1.5 points was selected based on previous long-term studies of duloxetine in DPNP  and CLBPIn addition, a mixed-model-repeated-measures (MMRM) analysis was performed to analyze the change in BPI average pain for all patients who entered the extension phase using data collected during the entire study (both the placebo-controlled and the extension phases). Type III sum-of-squares for the least-squares means was used and the last non-missing observation during screening was considered as baseline.The percentages of patients who achieved a ≥30% or ≥50% reduction in BPI average pain from baseline to endpoint were summarized. Here, the baseline and endpoint were defined as the last non-missing observation during screening and the last non-missing observation during the extension phase, respectively.From a total of 407 randomized patients, 39 patients from the DLX group and 26 patients from the PLA group discontinued the study during double-blind phase, and a total of 342 (166 in the DLX group and 176 in the PLA group) entered into the open-label extension phase . Among tDemographic and clinical characteristics were comparable between the groups (PLA_DLX and DLX_DLX) at baseline of the placebo-controlled phase Table . All patTwo (1.2%) DLX_DLX-treated patients and 2 (1.1%) PLA_DLX-treated patients were taking at least 1 short-acting analgesic during the extension phase. In the DLX_DLX group, 1 patient took acemetacin 90 mg/day for 8 days and 1 patient took diclofenac sodium 150 mg/day for 2 days. In the PLA_DLX group, 1 patient took loxoprofen 180 mg/day for 2 days and 1 patient took 3 units/day of paramol-118 for 3 days.p < 0.001) less compared to the non-inferiority margin, which was prespecified as 1.5-points increase on BPI average pain. This indicates that in those patients who responded to duloxetine during the placebo-controlled phase, the treatment effect of duloxetine 60 mg QD on pain reduction was maintained over the 13-week extension phase. In addition, since the upper bound of the 1-sided 97.5% CI was < 0, the pain severity was statistically significantly reduced during the extension phase versus the end of the placebo-controlled phase.A total of 113 patients in the DLX_DLX group met the 30% response criterion after the 13-week placebo-controlled phase. Among these patients, the mean BPI average pain changed from 2.47 to 1.88 during the extension phase . The upper limit of the 1-sided 97.5% CI was significantly , BPI–Interference average rating, and all 7 individual BPI–Interference items Table .Table 2MTable No deaths or suicide-related events were reported during the extension phase. DLX_DLX patients did not experience any SAEs or discontinue the study due to an AE. Two (1.1%) PLA_DLX patients experienced four SAEs, including 1 incidence each of fall, lacunar infarction, skull fracture, and vertebrobasilar insufficiency. Seven (4.0%) PLA_DLX patients discontinued the study due to an AE. No AE led to study discontinuation in more than 1 patient, except for nausea in 2 patients. Taken together, these data suggest that the incidences of SAEs, AEs leading to discontinuation, and TEAEs including those commonly observed with duloxetine treatment, were lower in patients with long-term (6 months) exposure to duloxetine compared to those with short-term (3 months) exposure during the extension phase, although statistical comparison between treatment groups was not performed.Seven (4.0%) PLA_DLX patients and 3 (1.8%) DLX_DLX patients reported at least 1 fall at the end of the extension phase. Five of the 10 patients reported an AE of fall or ligament sprain, among which one led to hospitalization and thus considered as an SAE. None of the AEs or SAE was related to the study drug or protocol procedures as per the investigators’ judgment.Vital signs were stable relative to the end of the placebo-controlled phase. No patients in the PLA_DLX group had sustained (3 consecutive visits) elevations in either diastolic or systolic blood pressure, whereas 1 (0.6%) patient in the DLX_DLX group had sustained elevations in systolic blood pressure. Twenty-five (14.3%) PLA_DLX patients and 17 (10.2%) DLX_DLX patients experienced orthostatic hypotension.No DLX_DLX patients had ALT ≥3 times upper limit of normal (ULN) during the extension phase. Three (1.9%) PLA_DLX patients had treatment-emergent ALT ≥3 times ULN, and 1 of them had ALT ≥10 times ULN. All 3 patients completed the study. Two of the 3 patients had their ALT levels decreased to < 2 times ULN and 1 patient had the ALT level return to normal at the end of the extension phase. No clinically relevant changes were observed for other chemistry analytes.Duloxetine-treated patients with OA pain who were responders during the placebo-controlled phase benefited from continuing treatment with duloxetine 60 mg QD in the 13-week extension phase of this study. The upper limit of the group mean change in BPI average pain was lower than the priori-specified non-inferiority margin, demonstrating that the pain reduction from duloxetine treatment obtained at the end of the initial 13 weeks was maintained during the subsequent 13-week extension phase. From the individual patient level, of the 113 placebo-controlled-phase responders, 105 maintained ≥30% pain reduction at the end of the extension phase. Moreover, the upper limit of the group mean change in BPI average pain was less than zero, suggesting a statistically significant pain reduction from the end of the placebo-controlled phase to the end of the extension phase, thus further highlighting the importance of continuing duloxetine treatment over time.Two previous duloxetine studies observed improvements or minimal worsening in pain measures in patients with fibromyalgia in the 6-mounth extension phases . Pain reOnly two patients in each treatment group were taking at least 1 short-acting analgesic during the extension phase, which is much fewer than those observed in previous studies in DPNP and CLBP , 33. OneThe safety and tolerability profile of duloxetine during the extension phase was comparable with that observed in the placebo-controlled phase of this study and in the previous studies of duloxetine for other chronic pain conditions , 33, 35.Seven PLA_DLX patients and 3 DLX_DLX patients reported at least 1 fall at the end of the extension phase. Falls have been reported with therapeutic doses of duloxetine . The risOne of the limitations of this study is that the extension phase was open-label and uncontrolled. Because the lack of blinding may have introduced a bias in the evaluation of maintenance of effect and of the safety profile, findings from the extension phase should be interpreted with caution. However, placebo-controlled studies in pain are always of limited duration due to ethical and practical concerns. Another limitation is that this study included only Chinese patients and excluded patients with certain psychiatric or medical disorders, so results should be extrapolated with care to the general population. Finally, the extension phase only lasted for 13 weeks. Future studies with longer duration may investigate whether the analgesic effect of duloxetine can be maintained in patients with OA pain for longer time.Chinese patients with OA pain maintained the improvement in pain measures that occurred in the 13-week placebo-controlled phase during 13 weeks of continued treatment with duloxetine. Moreover, additional pain relief was observed during the extension phase, further highlighting the importance of treatment continuation. Duloxetine was well tolerated during long-term treatment and demonstrated a safety profile similar to that observed in previous clinical trials.


The purpose of the study was to explore the effect of kinesiology taping on hemiplegic shoulder pain (HSP) in terms of pain intensity, magnitude of subluxation, muscle activity, and active range of motion (AROM).  Double-blind, placebo-controlled clinical trial.  the Rehabilitation Center of the West China Hospital.  Nineteen individuals suffering from HSP were recruited in this study.  Patients were randomly assigned into the taping group or control group. The taping group received therapeutic kinesiology taping and conventional treatment, while the control group received placebo taping (applied without tension) and conventional treatment.  The shoulder pain intensity , magnitude of subluxation, muscle activity (measured by surface electromyography (sEMG)), and shoulder active range of movement (AROM) were assessed at the baseline, on the first day (immediately after taping) and 4 weeks after treatment (without taping). p < 0.05), whereas no significant changes seen in the control group (p > 0.05). After 4 weeks of treatment, the taping group showed significant changes in pain intensity, magnitude of subluxation, muscle activity, and AROM (p < 0.05). And significant differences in pain intensity and muscle activity could be seen between the two groups (p < 0.05).  All patients completed the trials. There were no significant differences between groups at the baseline. The taping group showed immediate improvement on the first day after taping in terms of pain intensity, magnitude of subluxation, and muscle activity ( The results indicate that the kinesiology taping is effective in reducing the shoulder pain and subluxation and increasing muscle activity and AROM for patients with HSP after stroke. Shoulder pain is a common complication in hemiplegic patients after stroke. The incidence of hemiplegic shoulder pain (HSP) is reported to be approximately 17–72% . HSP canThe mechanisms for HSP are not fully understood. Muscle weakness after stroke is believed to be a primary reason for HSP. As the shoulder muscles cannot contract effectively against gravity and external force during movement, the humeral head cannot be held in a proper position. Soft tissues around the shoulder may be gradually stretched and torn, resulting in HSP . This unRegardless of the limited understanding of the etiology of HSP, various therapeutic methods have been trialled to examine their effects on HSP. Different types of slings and strapping methods which can provide effective support to the shoulder are usually involved in the therapeutic strategy for HSP , 17. EleKinesiology taping, sometimes also called elastic taping, is a relatively new technique used in rehabilitation programs. This method is different from strapping or rigid taping technique. The elastic tape is a hypoallergenic skin tape with elastic components. This kind of elastic tape is designed to allow for a longitudinal stretch of 55–60% of its original extent. By using the kinesiology tape, different stretches and directions can yield different effects for reducing pain, correcting alignment, facilitating neuromuscular activity, and alleviating inflammation and edema –25. BaseA double-blind, placebo-controlled clinical trial was carried out to investigate the effects of kinesiology taping on HSP. The blind method was used for the patients and therapists who provided conventional treatments and assessment. The primary outcome measurement was set as the pain intensity of the shoulder, and the secondary outcome measurements included the magnitude of subluxation, active range of motion (AROM), and muscle activity of the shoulder.The study protocols were approved by the Ethics Committee of the West China Hospital of Sichuan University in China and were funded by the Sichuan Provincial Department of Public Health. And all participants provided written informed consent.The trial was carried out in the Rehabilitation Center of the West China Hospital from April 2013 to September 2014. Nineteen participants with a diagnosed first-ever stroke were recruited to the study. All participants met the following inclusion criteria: (1) > 30 years of age; (2) period after stroke: >1 month and <6 months; (3) diagnosed as HSP with a period of more than 1 month, accompanied with shoulder subluxation; (4) adequate communication abilities; (5) the shoulder muscles can contract and move the shoulder more than 10 degrees but less than 90 degrees in flexion and/or abduction in sitting position, accompanying shoulder pain produced or increased; (6) normal light touch and pin-prick sensation on the affected shoulder; (7) the pain is caused by local problems: (1) manual palpation and movement can affect the pain and (2) reposition of the joint can relieve the pain.The exclusion criteria include (1) history of serious conditions or diseases such as cancer; (2) skin problems, wounds, or infections on the affected shoulder; (3) skin allergy to the tape; (4) history of shoulder fracture on the affected side or history of shoulder sprain or subluxation before the stroke; (5) severe disease which may affect the study, such as uncontrolled hypertension or heart disease; (6) history of intra-articular steroid injection in the past 4 weeks.According to the recruited order and the corresponding random number sealed in an envelope, patients were assigned into the taping group or the control group. Before treatment, the demographic data and clinical characteristics of the participants were recorded. The outcome measures were assessed at the following time points: at the baseline (one day before the treatment), on the first day , and after 4 weeks .All the participants received treatment once a day, 5 days per week for 4 consecutive weeks. The treatment program included kinesiology taping, electrical therapy, and exercise treatment. Electrical therapy was applied first, followed by taping and finally exercise. The therapeutic taping was used for the taping group, while placebo taping (without tension) was applied for the control group.Exercise therapy for the affected shoulder included passive and active assistant and active exercises. These exercises focused on restoring and improving the motor function of the shoulder. The range of motion (ROM) exercise of the affected shoulder was demanded to be less than 90 degrees to avoid potential injury to the joint. The exercise time for the affected shoulder was 20 min. The patients also received 40 mins exercise for the trunk and low limb.Electric therapy  was applied in the study. The electrodes were placed over the posterior and anterior aspects of the shoulder. The pain-reduce program was chosen for all patients. The treatment time was set to 20 min, and the output current was set to 20–40 mA.The therapeutic taping aimed to activate the neuromuscular function and produce mechanical support to the shoulder. Tapes of 5 cm width were used for patients. The taping method is shown in Shoulder pain was the primary outcome measure and was assessed by a numerical pain rating scale (NPRS) which has a high correlation coefficients with the visual analog scale and is simple to use . The paiThe patient was kept unsupported in an upright posture without a backrest or armrests, with the arms in a neutral position hanging by the side of the body. The inferior border of the acromion and the highest of greater tubercle of the shoulder was palpated and marked. The vertical distance between the two points was measured with a tape measured and recorded. The difference of the distance between the affected and normal sides was defined as the magnitude of subluxation.In a sitting position, the patient was instructed to first flex and then to abduct the affected shoulder as much as possible. The AROM of the affected shoulder in flexion and abduction was measured with the goniometer and recorded.μV), was calculated for further analysis.Electrical sensors have emerged as an efficient way to characterize biomedical signals. The muscle activity was assessed with sEMG. The Muscle Tester ME6000  was used for the purpose of the study. The muscle electrical activation of the middle part of deltoid and supraspinatus muscles during shoulder abducting in sitting position was recorded. Prior to the test, the skin was cleansed with 75% alcohol. Disposable 8 mm AgCI surface electrodes  were attached over the middle part of deltoid and supraspinatus muscles on the affected side. Sampling of the muscle activity was done at a frequency of 1000 Hz. The data were downloaded to an EMG analyzer, Megawin 2.5 , where the data were analyzed. The average amplitude, which was presented with AEMG . The chi-square analysis was used to determine the group difference in sex and side of hemiplegia. Paired sample Totally, 19 patients were recruited in the study. The demographic characteristics and measurements at the baseline are shown p < 0.05), whereas there was no significant changes in the control groups in these outcomes. Both groups showed no significant changes in the AROM in flexion and abduction on the first day (p > 0.05). After 4 weeks of treatment, significant improvement was seen in the taping group in terms of pain intensity, magnitude of subluxation, AEMG, and AROM (both flexion and abduction). Based on the baseline, the amount of improvement in the pain intensity, magnitude of subluxation, AEMG, and AROM were significantly greater than the control group (p < 0.05).Based on the data listed in Tables 2∗Power. The calculation was based on the primary measure, NPRS. The power is 0.99 which indicates that power level is acceptable, and the sample size is enough for this study.The statistical power was calculated by using the software GTo our knowledge, this is the first study aimed at exploring the effects of kinesiology taping on HSP in terms of pain, shoulder subluxation, AROM, and muscle activity of the shoulder. The results indicated that kinesiology taping is an effective method for HSP management.It has been noticed that some other types of taping methods were trialled to examine their effect on HSP. Despite the difference in tapes and taping methods, most of these studies focused on the effect of taping on preventing the development of HSP , 28. As p < 0.05) was observed immediately after taping was applied on the first day. The immediate effectiveness of kinesiology taping in modulating pain was reported in previous studies focusing on treating impinged shoulder pain, neck pain, and low back pain [Actually, kinesiology taping has been widely used to treat musculoskeletal problems. Its effects on nonspecific pain, such as neck pain, impinged shoulder pain, and knee pain, have also been examined. In the present study, a significant reduction of pain (NPRS, from 4.3 points to 0.3 points, ack pain , 29–31. ack pain . In addiack pain , 34. TheBesides the reduction in pain intensity, kinesiology taping also yielded notable decrease of subluxation. Even though the reliability and validity of the method for assessing the subluxation have not been examined, considering the blind method was applied to the assessor and patients, the results have credibility for discussion. The alignment correction effect of taping has been widely examined and accepted , 35. RedIn addition, the muscle activation effect of kinesiology taping has been discussed and studied. Macgregor et al. designed a study to investigate the effect of taping on muscle activity in people with patellofemoral pain. Results demonstrated that stretching to the skin via taping can increase muscle activity . Some otDespite the immediate improvement in pain, subluxation, and muscle activity, no significant changes in AROM were observed after tapping. It is out of our expectation that, along with the significant reduction of pain, the AROM shoulder increased correspondingly. It is known that pain is an inhibiting factor to the neuromuscular activity  and the There were some limitations in the present study that should be noted. First, the characteristics of the patients in this study met specific criteria. For example, only patients whose pain can be reduced by joint reposition were recruited. Second, there was no special examination, such as X-ray or ultrasound, adopted in the study to document the shoulder injury and healing. Third, the sample size was small, and all participants belonged to the same hospital. Finally, only 4 weeks of treatment was conducted, without long-term follow-up data. Hence, the ability to generalize the findings in the present study to the poststroke population is limited.The present study revealed the effectiveness of kinesiology taping for HSP. Kinesiology taping might be a good alternative for relieving shoulder pain, improving the AROM, subluxation, and muscle activity of the shoulder in patients with HSP after stroke.