Total Knee Arthroplasty (TKA) is a common and generally effective procedure performed mainly due to advanced osteoarthritis, pain, physical disability and reduced quality of life. However, approximately 20% of the patients respond poorly to the surgery and chronic pain and disability following TKA remains a major health burden for many patients. Among the most well documented and powerful psychological predictors of poor outcome following TKA is pain catastrophizing. Recent research has shown that patients with these thoughts are at higher risk of having persistent pain and lower physical function after the operation than patients with low levels of pain catastrophizing before TKA. There is high need of developing treatments aimed at improving self-management for this group of patients and the aim of this study is to investigate the effectiveness of a patient education in pain coping on physical function and pain among patients with high pain catastrophizing score before a TKA.This study is a two-arm parallel group trial design including 56 patients with high levels of pain catastrophizing referred for total knee arthroplasty due to osteoarthritis. Patients eligible for participation will be randomized into the two arms, usual care or usual care and patient education. Usual care consists of operation and standard rehabilitation. The patient education consists of 7 individual sessions focusing on pain behavior and pain coping managed by a physiotherapist. Three before the operation and four after. Measurements will be taken at baseline before the operation and 3 and 12 months after the operation. Primary outcome will be pain after 12 months measured with VAS . Secondary outcomes include physical function and activity, quality of life, pain management and psychological factors.Only few studies have evaluated the effectiveness of psychological interventions on patients with high levels of pain catastrophizing before the operation. This trial will provide evidence for the effectiveness of a cognitive-behavioral patient education delivered by physiotherapists and may provide better functional outcome and less pain for a vulnerable group of TKA patients. We expect that the results can provide important new knowledge to the current care recommendations.NCT02587429). Registered 23 October 2015Clinical Trials ( Total Knee Arthroplasty (TKA) is a common and generally effective procedure and most of the operated patients have less pain and higher functional ability after the surgery . HoweverCognitive Behavioural Therapy (CBT) is one of the most widely accepted models in the field of pain psychology and the biopsychosocial approach of CBT focuses on the complex interaction between psychological , social  and biological  factors. The biopsychosocial model assumes that health problems are hardly ever limited to just one domain of human experience but by multiple domains of human experience. CBT is a treatment that helps patients understand the thoughts and feelings that influence behaviors. CBT consists of a cognitive aspect and a behavioural aspect. The cognitive aspect is based on Becks cognitive model : the wayPsychological interventions as CBT that train patients in pain coping produce significant reductions in pain and improvements in self-efficacy and psychological well-being in individuals with knee osteoarthritis (OA) –23. HoweThis study is a single centre double-arm parallel group design trial with 1:1 allocation with 1-year follow-up. Measurements will be taken at baseline before the operation and 3 and 12 months after the operation.We will recruit 56 patients from the Orthopedic outpatient clinic at Holstebro Regional Hospital.Be able to speak, talk and understand Danish language.Provide informed consent.Have a primary diagnosis of osteoarthritis.Be scheduled for an elective unilateral total knee arthroplasty.Age ≥ 18 years.A score >22 on the Pain Catastrophizing Scale (PCS).To be eligible for inclusion the patients must fulfill the following criteria:Severe depression (at least three core symptoms and two accompanying symptoms) diagnosed with the Major Depression Inventory (MDI) .Scheduled for revision arthroplasty.Scheduled for a unicompartmental arthroplasty.Planning to have a contralateral knee arthroplasty within 1 year from the operation.Have a diagnosis of inflammatory arthritis.Patients eligible for participation will be randomized into the two arms, usual care or patient education Fig. . The patRandomization will be conducted by permuted blocks and an independent staff will prepare consecutively numbered, sealed envelopes. The physiotherapists and nurses who execute the baseline and follow-up testing will be blinded for the randomization. The patients and the three physiotherapists delivering the pain coping education cannot be blinded.Patients will be screened preoperatively at the outpatient clinic after they are scheduled for a TKA using the questionnaire Pain Catastrophizing Scale (PCS) . PCS conThe cut-off score for PCS is chosen on basis of data collected in the years 2011–2013 at Holstebro Regional Hospital. 530 TKA patients answered the PCS before the operation. Median PCS score was 16 range (0–52). In the present trial we want to include the 33% of our TKA population with the highest PCS score. This means that we will use the 66th percentile of the total score to define the cut-off in this study. Thus, patients with a PCS score on 23 or higher are eligible for inclusion and in this study defined as patients with “high pain catastrophizing”.Patients in the control group will receive usual care. This consists of a multidisciplinary information meeting for patients and their relatives, approximately 1 week before the operation. After the operation the patients have contact with the hospital 4 times. Seven days , 14 days, 4 weeks and 3 months after the operation they will be called in for a control visit with the nurse, physiotherapist and operating surgeon respectively. Further, some of the patients will receive physical rehabilitation in their local community.The intervention group will in addition to the described usual care participate in a patient education based on cognitive-behavioral therapy. We wanted to design a patient education that fits into a hospital setting with relatively few session contrary to previous studies were the CBT intervention most commonly range from 10 to 12 sessions , 23, 29.The same physiotherapist will follow the patient through all the 7 sessions. To make sure that the physiotherapists will all deliver the intervention in the same way they will be observed by each other on a regular basis.The three physiotherapists will follow a pre-specified manual containing the content of each of the seven sessions. Though the manual will leave some flexibility to discuss the patient’s individual needs and problems in each of the sessions. The content of the manual is inspired by Rolving et al. . In the The patient education involves three main components: a) education about pain and the role pain coping skills can play in pain management, b) systematic training in a variety of cognitive and behavioral pain coping skills, c) training in how to apply learned coping skills to real life situations that are particularly challenging to the patient.The goal of the patient education is to teach the patients about pain in order to gain a better understanding of how cognitions and behavior affect the pain experience. We want them to understand the link between thoughts, feelings, bodily reactions and behavior and to realize their own role in controlling their pain experience. The patients shall learn to use appropriate coping strategies such as activity pacing and pleasant activity scheduling to increase their activity level and observe the resultant impact on their pain related cognitions. Additionally, the patients will be trained in cognitive restructuring. Using techniques drawn from cognitive therapy the patients will be taught how to identify irrational, maladaptive and catastrophic related thoughts that contribute to pain and how to replace them with alternative rational and more positive thoughts. Each patient will learn about their own early warning signs of setbacks and potential high risk situations and how to use the coping skills learned in the seven sessions to deal with future challenges.The data presented in Table Secondary outcomes will be several self-reported questionnaires: SF-36  , Oxford The primary outcome measure will be VAS under activity measured on a continuous 100 mm scale 12 month after the operation. Clinically important differences between the two groups is detected to be 18 mm , 47. BasClinical and demographic characteristics as well as baseline data will be presented to show the baseline comparability of the two groups. Data from the patients who withdraw from the study will also be examined. For each group descriptive statistics will be presented at baseline and three and 12 months postoperative. Normally distributed data are described by means and standard deviation (SD), and data not normally distributed by medians and interquartile range (IQR). The primary analysis will use the intention-to treat principle including all randomised participants. Patients who discontinue the intervention will be encouraged to participate in the follow up test anyway, and those who accept will be included in the analyses according to their original group assignment. The primary outcome pain is measured on a continuous scale and between-group mean differences and 95% confidence intervals from baseline to 3 and 12 months will be analyzed by a mixed effects linear regression model with a random person level and systematic effects of time, group and the interaction between time and group. We will employ multiple imputation methods in order to assess the sensitivity of the mixed model to any informative missing values. Imputations will be performed using baseline characteristics and non-missing pain measurements on individual levels. Secondary outcomes will be analysed as above for normally distributed measures or for binary outcomes, we will use logistic regression with a robust variance estimate to account for the repeated measurements. Standard diagnostic plots will check model assumptions. The statistical analyses will be performed using STATA 13  software package. The significance level will be set at 0.05.www.clinicalTrials.gov (NCT02587429). The study will be conducted in accordance with the Good Clinical Practice Guidelines and the Declaration of Helsinki. All patients are ensured minimum standard treatment and the patient education carries no risk to the patients.The study is approved by The Central Denmark Region Committee on Biomedical Research Ethics  and The Danish Data Protection Agency and is registered at Knee OA is one of the most common forms of arthritis and an increasing proportion of older people have to live with chronic diseases in the future. This will carry a major economic burden for the healthcare system and recent research shows that there is high need of developing treatments aimed at improving self-management for a selected group of patients at high risk of having long-term pain and physical disability after a TKA. CBT interventions are traditionally delivered by psychologists and using physiotherapists to deliver psychological interventions is fairly novel. However, physiotherapists have a history of teaching patients about pain and pain coping. Further, they normally see the patients several times in connection with the operation and taken into account the high number of TKA operations and the limited availability of psychologists at the hospital physiotherapists are highly qualified to provide this patient education. Recent studies shows that both nurses and physiotherapists are sufficient to deliver high standard pain coping skills training , 49.This study design has several strengths. First, the patients are screened on basis of their risk of having chronic pain after the operation. Only patients with high levels of pain catastrophizing will be eligible for the patient education and the education will be targeted these patients. Second, the outcome measures are valid and reliable, and include a range of both self-reports and objective measures. Third, there has only been few studies evaluating the effect of psychological interventions on knee OA pain and no RCT’s evaluating the effect on patients with high levels of pain catastrophizing. Thus, good RCT’s are needed to determine the effectiveness.There are some limitations as well. First, due to the different amount of attention paid to the patients in the two groups, a Hawthorne effect is possible , 51. HowWe consider the external validity of the trial to be high while the treatment of TKA patients is almost similar all over the country. This makes it easier to implement at other Hospitals.This project is expected to improve the overall treatment effect for a group of patients we today do not know how to treat the best way. We hope that this study can provide better functional outcome and less pain for the patients after the operation and that the study can produce new knowledge and inspire similar developments of interventions to other diseases.


The stratified model of care has been an effective approach for the treatment of low back pain. However, the treatment of patients with low risk of psychosocial-factor involvement is unclear. The addition of the therapeutic alliance to a minimal intervention may be an option for the treatment of low back pain. This paper reports on the rationale, design and protocol for a randomized controlled trial with blind assessor to assess the effectiveness of the addition of therapeutic alliance with minimal intervention on pain and disability in patients with chronic, nonspecific low back pain.n = 74 patients per group). The Positive Therapeutic Alliance group will receive counseling and guidance with an emphasis on therapeutic alliance and empathy. The Usual Treatment group will receive the same information and counseling with limited interaction with the therapist. The Control group will not receive any intervention. The treatment will be composed by two intervention sessions with a 1-week interval. A blinded assessor will collect the following outcomes at baseline, 1 month, 6 months and 12 months after randomization: pain intensity , specific disability , general disability (Oswestry Disability Index), global perceived effect , empathy , credibility and expectations related to treatment. The analysis will be performed using linear mixed models.Two hundred and twenty-two patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors will be assessed and randomly allocated into three groups . The addition of the therapeutic alliance to minimal intervention may improve the treatment of chronic, nonspecific low back pain.ClinicalTrials.gov, NCT 02497625. Registered on 10 July 2015.The online version of this article (doi:10.1186/s13063-017-1784-z) contains supplementary material, which is available to authorized users. Low back pain remains a global public health problem . It is cLow back pain is an ideal condition for the stratification of treatment subgroups since it is a condition that affects a heterogeneous population, presenting prognostic variation and relying on different diagnostic options and available treatments , 7, 8. SRecent studies have shown the cost-effectiveness of the treatment based on the chronic low back pain prognosis in patients with high and medium risks of developing chronic problems related to psychosocial factors , 14. PosThe extent of treatment effectiveness may be influenced by factors other than the intervention chosen. Contextual factors comprise the therapeutic effect of any intervention. These factors consist of a complex interaction between technical and communicative knowledge in addition to the therapist’s ability to meet the expectations of the patient during treatment . StudiesA recent study investigated the effects of increased therapeutic alliance and empathy in the treatment of patients with low back pain receiving active interferential current or a placebo. Patients were randomly allocated into four groups: (1) limited interaction plus active current, (2) limited interaction plus placebo, (3) increased interaction plus active current and (4) increased interaction plus placebo. The results showed clinical improvement associated with increased interaction between therapist and patient, which remained even with the application of placebo . This stAppropriate treatment for low-risk patients can provide important clinical benefits. It could be a fast and low-cost treatment option for the health system since it would help in identifying patients who do not require unnecessary or extensive assessment and treatment . To dateThis is a three-arm randomized controlled trial with blinded assessor. The patients will be divided into three groups: a Positive Therapeutic Alliance (PTA) group, a Usual Treatment (UT) group and a Control group (CG). Table α = 0.05, a statistical power of 80% and a follow-up loss of 15%. Thus, this study will comprise a sample of 222 patients who will be divided into three treatment groups (n = 74 patients per group).The sample size calculation was carried out to detect a difference of 1 point on the Pain Numerical Rating Scale (estimated standard deviation = 1.84) and 1 point on the Patient-specific Functional Scale (estimated standard deviation = 1.8). The calculations were performed considering an This study will be carried out with patients on the treatment waiting lists of two physical therapy teaching clinics in the city of Taubaté, São Paulo (approved by the Ethics Committee of Universidade Bandeirante Anhanguera n. 44720315.5.0000.5372). The patients will be invited personally by phone. This study will include patients who have had chronic, nonspecific low back pain for at least 3 months, aged between 18 and 80 years, and who are able to read and write in Portuguese and classified as low risk of having psychosocial factors involved , 31. PatPatients will be evaluated by a previously trained blinded assessor who will provide information on the procedures and criteria for study participation. The assessor will contact patients by phone to confirm their eligibility criteria and to fill out the SBST-Brazil questionnaire. In the case of acceptance of participation and compliance with the eligibility criteria, the patient will be forwarded to initial assessment.The blinded assessor will collect data at the baseline utilizing a neutral communication style so as not to influence the therapeutic alliance involved in patient care. A coding system in follow-up assessments will be carried out to ensure blinding. After this initial procedure, eligible patients will be referred to the therapist responsible for the interventions. An independent researcher not involved in the recruitment and evaluation of patients will perform randomization using Microsoft Excel software random number generation. The secret allocation will be made using sequential, numbered, sealed opaque envelopes. Due to the nature of the study, it will not be possible to blind the therapist or patients. All researchers involved in the stages of this study will receive adequate training to carry out the activities. Patient recruitment will begin in September 2015 and the date of completion will be December 2016.The elegibility criteria, collection of demographic and anthropometric data from the patients as well the outcomes will be conducted by a blinded assessor. The randomization to the treatments groups will be done before the initial evaluation. The assessor will be aware of the allocation only after data analysis.All the questionnaires and scales used to assess primary and secondary outcomes have been translated and adapted into Brazilian-Portuguese and have shown adequate measurement properties. The primary outcomes of this study will be pain and specific disability after 1 month of randomization. The study’s secondary outcomes will be pain and specific disability 6 and 12 months after randomization; and general disability and perceived global effect 1, 6 and 12 months after randomization. Empathy, credibility and expectations related to treatment will be used as additional outcomes.The initial assessment information will include age, gender, height, weight, educational level and job information related to low back pain .The SBST-Brazil questionnaire is a prognostic evaluation tool which aims to classify patients into low, medium or high risk of developing long-term pain or disability related to psychosocial factors , 31. TheThe Pain Numerical Rating Scale is a scale of 11 points (0–10) that aims to measure the intensity of pain reported by the patient, where 0 = “no pain” and 10 = “pain as bad as could be” . In thisThe Patient-specific Functional Scale provides reliable measurements of limitations in specific tasks . The patThe Oswestry Disability Index aims to assess disability associated with low back pain , 36. ThiThe Global Perceived Effect Scale seeks to evaluate clinical changes perceived by the patient by comparing the onset of symptoms to the current situation . It is aThe Consultation and Relational Empathy (CARE) Measure is a questionnaire to assess patients’ perception of empathy and communication during consultation –39. It cImprovement expectation will be assessed by a numerical scale of 11 points, with 0 = “no expectation of improvement” and 10 = “the highest expectation of improvement” . CredibiPatients will be randomized into three groups: a Positive Therapeutic Alliance (PTA) group, a Usual Treatment (UT) group and a Control group (CG). Treatment sessions will be conducted face-to-face and individually with each patient. The treatment sessions will be delivered by two physical therapists with postgraduate qualifications and a completed Master’s degree in the research field.The treatment protocol offered to the PTA and UT groups will be based on research that demonstrates the effectiveness of empathy and communication training with patients –28, 41. The Back Book [The Back Book [The patients in the PTA group will undergo an intervention based on treatment guidelines involving guidance and information related to a return to daily activities, advice on dealing with the pain and clear explanation of their signs and symptoms , 42, 43.ack Book . PatientPatients who require additional interventions other than those offered by this study will be referred for treatment at teaching clinics of the participating universities. Patients’ use of medication will not be limited and will be controlled at each reassessment. Patients will be advised not to seek other treatment options during the intervention period. Patients will not receive any financial compensation for participation.A researcher not involved in data collection and without any conflict of interest will be responsible for monitoring data. The randomization process and blinding of patients and assessors will be audited monthly by an experienced researcher. All data will be entered twice before statistical procedures. A researcher who will receive the data in an encrypted format to ensure confidentiality will conduct the statistical analysis.Linear mixed models will be used for primary analysis to verify the differences between the average effects of interventions in reassessments carried out 1 month, 6 months and 12 months after randomization. The differences between groups will be calculated by interaction terms of groups versus time. The time will be coded as a categorical variable . No interim analysis will be performed. The process of analysis of treatment efficacy will follow the intention-to-treat analysis . If a paThe results of this study will help us to understand the effect of combining increased therapeutic alliance with a type of treatment based on advice, information and advice for patients with chronic low back pain and low risk of psychosocial-factor involvement. We believe that the UT group will present significantly better treatment results when compared to the CG. Regarding the PTA group, the study hypothesis is that: 1 month after randomization, there will be a significant clinical decrease in pain and especially in specific disability, when compared to the other two study groups. This assumption is based on recent studies, which have shown that the therapeutic alliance does in fact have a positive influence on clinical outcomes of patients with irritable bowel syndrome , rehabilIt is known that a minority of patients who develop chronic pain are responsible for most of the treatment-related costs , 6. It iRecruitment started in September 2015 and is expected to continue until December 2016.


First bite syndrome, characterized by pain in the parotid region after the first bite of each meal, predominantly develops in patients who have had head and neck surgery. Idiopathic parotid pain (IPP) that mimics first bite syndrome may present in patients without a history of surgery or evidence of an underlying tumor, but its clinical features are unclear. This study characterized the clinical characteristics of IPP in patients with diabetes. A retrospective case review involving the clinical findings and pain characteristics of nine patients with IPP and diabetes who presented to our department between 2013 and 2016. All the patients were men diagnosed with type 2 diabetes . IPP developed unilaterally in seven patients and bilaterally in two. The median intensity of the first bite pain was 8 on a numerical rating scale of 0–10. The trigger factor was gustatory stimuli, and the trigger area was the posterior section of the tongue. Postprandial pain occurred within 1–10 min after meals in six patients. IPP may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different.  First bite syndrome is a rare pain syndrome that is characterized by severe paroxysmal pain in the parotid region, which is precipitated by the first bite of each meal and diminishes in severity with subsequent mastication –7. FirstFirst bite syndrome has previously been described as a complication of surgery of the upper cervical region involving the infratemporal fossa, parapharyngeal space, and parotid gland –7. AdditCases of IPP have been mainly reported in patients with diabetes , 14. DiaWe conducted a retrospective case study to determine the clinical findings and pain characteristics of IPP. The study was performed in accordance with the standards of the Declaration of Helsinki and was approved by our institutional review board (2016-3-25).Fourteen patients with IPP who presented to the authors' orofacial pain clinic between January 2013 and December 2016 were enrolled in this study. All medical records were reviewed retrospectively. Patients received a definitive diagnosis of IPP if they met the following criteria: (1) parotid pain that coincided with the first bite of every meal and subsided over the next several bites; (2) the absence of salivary gland, masticatory muscle, temporomandibular joint, or dental pathology capable of causing the facial pain; (3) no history of injury or surgery in the head and neck region; and (4) no evidence of tumor arising from the salivary glands or the parapharyngeal space. Five patients were excluded as they did not have diabetes, and therefore, nine patients were finally included in this study.R-R]), imaging findings, pain characteristics, and course of IPP.We analyzed patient characteristics , clinical symptoms, laboratory findings  of the head and neck on a 1.5-T imaging system. MRI studies were reevaluated with a particular focus on the salivary glands, parapharyngeal space, temporomandibular joints, and course of the trigeminal and glossopharyngeal nerves.Information about the status of diabetes before the onset of IPP was obtained from the patients' physicians. Diabetic control was considered good when HbA1c was less than 7 . CardiovPatients were asked to rate the severity of pain intensity and the degree to which pain interfered with their eating during the past one week using a 0–10 numerical rating scale (NRS), with “0” denoting “no pain” and “10” denoting “pain as bad as you can imagine” with respect to pain intensity and with “0” denoting “does not interfere” and “10” denoting “completely interferes” with respect to interference with eating. The improvement in IPP was based on the reduction in the degree of parotid pain. P value < 0.05 was considered to be significant. All statistical analyses were performed using the JMP statistics software program version 12 for Macintosh .Continuous variables were expressed as median and range. Wilcoxon signed rank test was conducted to evaluate the changes in pain level before and after treatment, and aPatient characteristics are shown in All patients had type 2 diabetes. The median duration of diabetes was 7 years . Two patients received no diabetes care (cases 2 and 9). Seven patients were treated with several types of antidiabetic medications, none of which had a side effect of parotid pain; however, diabetic control was poor before the onset of IPP. HbA1c of three patients  was less than 7 at the first medical examination, but was more than 8 during the several months before the onset of IPP. In addition to the treatment of diabetes, severe IPP made eating difficult, consequently leading to a 6% significant decrease in HbA1c within two months in one patient (case 3). One patient was diagnosed with diabetic polyneuropathy (case 4), one patient had diabetic cataract (case 3), one patient had a history of foot cellulitis (case 6), one patient had renal disease (case 8), and one patient had diabetic retinopathy (case 9). Three patients had hypertension that was treated with blood pressure-lowering drugs . All patients were misdiagnosed as having parotitis, temporomandibular disorders, or dental pain by their dentist or physician.The clinical findings of this study are summarized in R-R was less than 2% in two of the six patients who underwent the test. Radiological examinations, including MRI, revealed no evidence of any underlying lesion of the head and neck in the any of the patients. Fat-suppressed T2-weighted images showed no increase in signal intensity in the parotid glands and no dilatation of ducts in any of the patients. Three patients underwent repeat MRI examinations of the head and neck, which confirmed the absence of abnormalities.The median of HbA1c and serum amylase concentration was 8%  and 55 U/l , respectively. CVPatients' pain characteristics are summarized in Tables First bite pain was confined to the parotid region in seven patients and radiated to the preauricular region in two patients. In all patients except for one patient (case 9), the parotid pain was evoked by applying a sour solution with an applicator to the posterior section of the ipsilateral tongue but not to the contralateral tongue. However, jaw movements and biting a cotton swab few times did not evoke the pain. Based on the NRS, the median intensity of the first bite pain was 8 . The median degree of interference with eating due to pain was 9 . The quality of the first bite pain was described as stabbing (three patients), sharp (two patients), smarting (two patients), or tightening (two patients).In six patients, the postprandial pain occurred on the ipsilateral side of location of the first bite pain within 1 to 10 min after meals. This pain was confined to the parotid region in one patient and the preauricular region in one patient. In the other four patients, the parotid pain radiated to the preauricular, temporal, or occipital regions. The median postprandial pain intensity was 8.5  on the NRS. The postprandial pain lasted from 2 to 30 min. The quality of the postprandial pain was described as stabbing (two patients), smarting (one patient), burning (one patient), or pricking (one patient); data regarding quality of postprandial pain were missing from the sixth patient's chart.One patient could not receive therapy owing to sudden change of residence (case 5). The remaining eight patients underwent dietary modification involving ingestion of bland food, avoidance of acidic foods, and chewing on the unaffected side. One patient responded to this dietary modification (case 9). The other seven patients required pharmacologic treatment mainly consisting of pregabalin or neurotropin . The two patients with untreated diabetes were referred to a diabetes specialist and underwent treatment for diabetes.P < 0.01) (P = 0.03). All the patients were generally able to eat a normal diet and reported the disappearance or decline of parotid tenderness.The first bite pain improved in all eight patients, who underwent treatment, and two of these patients reported complete relief from symptoms. The median pain intensity of the first bite pain before and after treatment improved from 8  on the NRS to 2.3  at the final follow-up visit, which was a significant difference ( < 0.01) . The posIn this study, we aimed to clarify the clinical features of IPP in patients with diabetes. We demonstrated that first bite pain in the parotid gland was triggered by nonnoxious gustatory stimuli and aggravated by mastication and that the trigger area was located on the posterior section of the ipsilateral tongue. IPP was severe enough to impair a patient's ability to eat. Of particular note is that all the affected parotid glands were sensitive to slight pressure, IPP developed bilaterally in two patients, and postprandial pain occurred in six patients.The results of the current study showed that the first bite pain of IPP was severe (a median score of 8 on the NRS) and lasted for a short duration (less than 1 min). The first bite pain of IPP was triggered by gustatory stimuli; acidic sialogogic foods triggered particularly strong pain. A recent retrospective study that evaluated 17 patients, who developed postoperative first bite syndrome after upper cervical surgery, reported that the pain severity ranged from 6 to 10 on the NRS, the duration of pain ranged between 3 seconds and throughout the meal, and the factor triggering pain was chewing and/or simple contact with food; these foods were always acidic [There are three main differences between the symptoms of IPP and those of postoperative first bite syndrome. First, in our patient group, all affected parotid glands were sensitive to slight pressure. All other clinical findings were normal, parotid imaging was unremarkable, and serum amylase was not elevated. We therefore ruled out the possibility of the inflammation or anatomical obstruction of the affected parotid glands. These findings indicate that the affected parotid glands were hypersensitive to mechanical stimuli, suggesting peripheral sensitization in or around the parotid glands. Interestingly, the improvement in the first bite pain of IPP was likely associated with the absence or decline of parotid tenderness. Second, our findings showed that the postprandial pain of IPP was of the same intensity as that of first bite pain, with a longer duration of pain, and larger affected area of pain than the first bite pain. This postprandial pain has not yet been described in postoperative first bite syndrome or malignant tumor-associated first bite syndrome –7, 9–12.The exact pathogenesis of first bite syndrome remains to be clarified, because the absence of animal studies and the rarity of first bite syndrome hinder a thorough understanding. According to Netterville et al. , who firδ and unmyelinated C fibers, including the autonomic nerves) are preferentially affected in the early stages of diabetes [The cause of the IPP cases in our study remains unknown. With regard to comorbidities that may contribute to IPP, nine out of 14 IPP patients were complicated with type 2 diabetes and presented hyperglycemia before the onset of IPP. Hyperglycemia is well recognized as a major cause of diabetic neuropathy . Small fdiabetes ; howeverdiabetes . In thisIn our study, all the patients with IPP and diabetes were men, suggesting that men are more likely to develop IPP. This may be attributed to the fact that, compared to women, men have more severe symptoms of diabetic neuropathy, have a higher incidence of diabetic neuropathy, and develop diabetic neuropathy earlier than women , 26. On The recurrent and severe pain associated with IPP sometimes prevents patients from eating, leading to inadequate nutritional intake and interference with diabetes management. In our opinion, impairment in eating and systemic health necessitates immediate treatment of IPP. Although limited data exist regarding the efficacy of pharmacologic treatment of postoperative first bite syndrome, anticonvulsants such as carbamazepine, pregabalin, and gabapentin used alone or in combination with tricyclic antidepressants have been shown to decrease the severity and/or duration of the first bite pain , 8. In oThis study has a few limitations. First, it was difficult to compare the clinical features of IPP between patients with and without diabetes because of the small number of cases. Second, the relationship between IPP and diabetes was speculated. Third, it was difficult to evaluate the therapeutic effects of the treatment for IPP, because patients received multiple treatments. Therefore, going forward, further studies involving a large number of patients are required to further elucidate the relationship between type 2 diabetes, gender, and IPP.The present study showed that IPP in Japanese patients with type 2 diabetes presents as first bite pain consistent with first bite syndrome, that IPP was induced by gustatory stimuli and aggravated by mastication, and that the trigger area was the posterior section of the ipsilateral tongue. The present study also demonstrated that the affected parotid glands were sensitive to slight pressure and that IPP developed bilaterally in two patients and postprandial pain occurred in six patients. IPP in patients with type 2 diabetes may be considered a separate disorder, in which the pain characteristics are similar to those of first bite syndrome but the clinical features and pathophysiology are different. Although IPP is a rare disease, pain clinicians should consider IPP as a differential diagnosis in patients presenting with first bite pain in the parotid region.


Current literature describes the limits and pitfalls of using opioid pharmacotherapy for chronic pain and the importance of identifying alternatives. The objective of this study was to identify the practical issues patients and providers face when accessing alternatives to opioids, and how multiple parties view these issues.n = 90) and primary care providers (PCPs) (n = 25) purposively sampled from a managed care health care system as well as from contracted community A/C providers (n = 14). Focus groups and interviews were conducted patients with CMP with varying histories of A/C use. Plan PCPs and contracted A/C providers took part in individual interviews. All participants were asked about their experiences managing chronic pain and experience with and/or attitudes about A/C treatment. Audio recordings were transcribed and thematically coded. A summarized version of the focus group/interview guides is included in the Additional file Qualitative data were gathered to evaluate the outcomes of acupuncture and chiropractic (A/C) services for chronic musculoskeletal pain (CMP) using structured interview guides among patients with CMP (ders n = 4. Focus We identified four themes around opioid use: (1) attitudes toward use of opioids to manage chronic pain; (2) the limited alternative options for chronic pain management; (3) the potential of A/C care as a tool to help manage pain; and (4) the complex system around chronic pain management. Despite widespread dissatisfaction with opioid medications for pain management, many practical barriers challenged access to other options. Most of the participants’ perceived A/C care as helpful for short term pain relief. We identified that problems with timing, expectations, and plan coverage limited A/C care potential for pain relief treatment.These results suggest that education about realistic expectations for chronic pain management and therapy options, as well as making A/C care more easily accessible, might lead to more satisfaction for patients and providers, and provide important input to policy makers.NCT01345409, date of registration 28/4/2011ClinicalTrials.gov The online version of this article (doi:10.1186/s12875-016-0566-0) contains supplementary material, which is available to authorized users. Chronic pain conditions are pervasive public health issues that exact a staggering human and economic toll. Indeed, persistent pain affects an estimated 19% of adults in the U.S. . The pasAlong with the rise in opioid prescribing for pain treatment  has comeRedirecting patients with chronic pain from opioid therapy toward behavioral and other non-pharmacologic modalities has proven challenging. This is partly due to the paucity of comprehensive chronic pain management programs . AdditioAlthough other non-pharmacotherapy options exist , 27, 28,While much of the current literature has focused on the problems associated with opioid medications, a growing body of work is examining how to mitigate risks of adverse outcomes and increase the potential effectiveness of other pain therapies. Despite this literature, little has been written about the practical issues providers and patients face when trying to access alternatives to opioids for managing chronic pain and how both patients and their various providers view these issues. This paper fills this substantial gap in the literature by describing and comparing patient, PCP, and A/C providers’ perspectives of the treatment of chronic pain as a complex system in the context of their experiences accessing alternatives to opioids.The goal of our analysis was to inform current debates about chronic opioid use for pain management and to describe the barriers providers face in changing therapeutic practice and CMP patients face in using such practices and co-managing their needs.The data for this paper were gathered during the early phases of a multi-phase, mixed-methods study to evaluate the outcomes of A/C services for CMP . This paThis study was conducted within a large managed care organization in the Pacific Northwest (Kaiser Permanente Northwest – KPNW). Nearly all of KPNW’s approximately 530,000 members have a chiropractic care benefit, and most (with the exception of Medicare patients) have an acupuncture benefit. Patients with musculoskeletal pain can be referred by a PCP or specialty physician to a contracted acupuncturist or chiropractor for a limited number of visits when clinically indicated. After referrals are vetted by the health plan’s referral office, patients make their own appointments with their chosen A/C clinicians.n = 90), PCPs who referred patients to A/C care (n = 25), and contracted community A/C providers who treated a high volume of managed KPNW’s CMP patients (n = 14). An accurate and more detailed discussion of the overall project methods and participant recruitment for this qualitative phase can be found in the overall project design paper  And then the pendulum swung the other way, noting that things like OxyContin were very, very addictive. And there were a lot of patients abusing the medicine, or just having real problems with it. And now, the trend is to really reduce people off the narcotics. [PCP 1]Participants’ experiences with chronic pain management occurred as clinical guidance and health plan resources were evolving. As one PCP described:In response, PCPs said that the health plan introduced several initiatives to reduce and better manage the use of opioid medications. Those included clinician education, periodic urine drug screening of patients, and implementation of written opioid therapy plans to be signed by the patient upon initiation of long-term opioid therapy. These changes positioned PCPs as the gatekeepers and monitors those therapy plans.The only options I’m given are, you know, like I’m going to be on pain medicines for the next fifty years. [PT 5–4]I got a ton of drugs thrown at me that I didn’t want. [PT 8–1]Across participant groups, however, respondents reported that despite efforts to discourage and more closely manage opioid use, medications (particularly opioids) were frequently the only option available and respondents from all groups were not satisfied with how they were managed.We don’t have very much to offer. […] We don’t have medicines that are really satisfying to give [patients] to help. And, you know, there’s limits on the type of therapy we can put them through. […] Really, all we end up having to offer them is chronic narcotic therapy, which is really dissatisfying to us. [PCP 14]We keep telling patients, you know, pain medication is only one part. There’s other modalities available. But we’re not reinforcing that. Majority of the time, patients still just get a pain medication. [PCP 2]One of the challenges PCPs reported was that while they can refer to pain management, physiatry, and other specialists to help manage complex cases, many CMP patients may already be taking substantial doses of opioids by the time such referrals are placed. PCPs also noted that barriers to other treatment options , coupled with patients’ desire for quick pain relief and PCPs’ discomfort with potential confrontations with patients should opioid prescriptions be refused, sometimes led PCPs to prescribe opioid medications or prescribe in larger quantities than they might have deemed optimal.Mostly when you work with a conventional medical doctor, it is about the prescriptions that the patient is on, because that’s kind of what they do. They know to put them on some kind of medication [CH 48]You have chronic pain! Oh, yeah? Well, who told you that? Oh, my doctor. Oh, okay. What did they do for you? […] They gave me Vicodin, you know, and they gave me some Flexeril. And they told me just to kind of rest, and it should get better. [CH 45]A/C providers echoed the perspectives of these two groups:Really with chronic pain, the easiest answer is to increase somebody’s narcotic. That’s fast and easy. They think they’re going to get better. They’re out of your office in two minutes. You’re done. But you’ve done a disservice for them long-term. [PCP 22]Most PCPs expressed negative attitudes towards opioids for CMP treatment. In describing patients’ trajectories of medication use to control their pain, many articulated a step-wise acceleration that included initial use of over-the-counter medications followed by graduation to opioids and stronger opioids as tolerance increased. While possibly the easiest course of action in a clinic visit, introducing opioids made the situation worse:PCPs said they would prescribe medications to help patients manage pain, but they stressed the need for patients to participate, engage, and assume responsibility during treatment. PCPs felt that opioid medication was an ineffective, long-term solution that fostered patients’ passivity and reluctance to do anything but take medications for pain management. Patient-driven action was described as the most important aspect of successful pain relief.Very often it’s very difficult to find something that works for them. And they end up, I’m hurting, I’m hurting, I’m hurting so much. And they end up wanting to slide into opioids. [PCP 16]PCPs continually pointed to patients’ beliefs in the effectiveness of opioids to reduce pain and the unwillingness of patients to actively manage their condition through lifestyle change as impediments to reducing opioid medications use.One of our most challenging patients […] we call them doctor shoppers. You know, their last doctor doesn’t want to keep prescribing their opiates, and so they try a new one. [PCP 7]PCPs described unrealistic patient expectations for zero pain, which if used to guide prescribing only led to increasingly powerful medications and doses being prescribed. Some providers referenced a subset of patients who were particularly manipulative and worked very hard to obtain opioid prescriptions. These individuals were characterized as having psychological and dependency issues and using medications inappropriately.Such patients might deceptively present themselves to the PCP to get prescriptions to feed their addictions or have mental health problems, such as anxiety, that escalated their sense of pain. These ‘problem’ patients, however, were difficult for clinicians to differentiate from other patients who used the medications appropriately. PCPs expressed discomfort with having to ‘play policeman’ and make these distinctions.I just need like Vicodin, or a pain med, on occasion. And I don’t like taking it. And I told my doctor that, that I wanted so I could sleep through the night. And now he, well, I’ll give you 10, but it’s got to last. Like he treats me like a drug addict. [PT 1-X]If you’re going to be able to walk, and you take one pain pill so you can walk and live life, you’re going to do it, even though you may not like it. [PT 2–5]While PCPs generalized about patients being drug seeking, patients’ attitudes toward opioids were much more complex, conflicted, and conditional.A lot of that medication makes me very drowsy too, so I have a hard time existing healthy-wise, with being like a zombie all the time, because I’m on all this medication. [PT 4–2]The immediacy of pain and the functional constraints that pain imposed on patients’ lives could lead them to use medications for a quick remedy, particularly if opioid medications had provided temporary relief in the past. At the same time, side effects of opioid medication  sometimes interfered with, rather than supported, functioning and quality of life.For other patients, opioids did not work for them. The variability of expectations of patients for pain relief and descriptions of compatibility between a person’s body and treatment type were reflected in the difficulty PCPs and A/C practitioners had identifying effective treatment for individual patients.A lot of the pain medications are addictive. And that’s the fear. […] I don’t want to be addicted to medication, narcotics. [PT 3–4]Patients also discussed the stigma attached to using opioid pain medication. They expressed frustration and discomfort with being treated suspiciously by their PCPs, such as when being restricted to a certain number of pills per month. Patients also illustrated the difficulties of stigma when they tried to legitimize opioid use during focus groups and interviews. For example, many who disclosed that they used opioids were quick to add qualifying statements regarding how they self-limited their use, used only as a response to genuine need (e.g. sleep problems), and never were “buzzed” by their usage. In doing so, these patients differentiated themselves from the stigmatized addicts that PCPs described and explained their usage in terms of how it supported their quality of life and ability to function. While many patients defended their opioid usage, they also expressed concerns about dependence.If [patients] come to me on oxycodone, then I’m not going to be able to get them off of that. [PCP 1]Usually, after about six months, we progress to providing them with some narcotic pain relief […] even though you tell [patients] it’s a one-way street, even though you tell them it’s kind of the road to perdition, sort of, they feel stuck and they feel like they have to do something to feel better. [PCP 14]Indeed, across participant groups, long-term opioid use was construed as highly problematic. Providers and patients often used the metaphor of a road to describe how the medication journey, once set upon, was hard to exit. This made medication use of any kind a somewhat daunting prospect, over which patients in particular expressed conflicted feelings. Notably, PCPs almost exclusively framed opioids as problematic because of the risk of dependence.By contrast, patients’ descriptions of fears of dependency were more nuanced and included discussion of the difficult costs and benefits they had to weigh when considering whether or not to take prescription opioids.timely patient access to the necessary system resources and with ultimate patient outcomes. Patients also cited the lack of access to other perceived effective therapies or to a structured process for tapering their dosages.Patients, like PCPs, expressed negative attitudes toward medications and some explicitly stated they wished to no longer have to take them. Despite this desire, tapering patients off medications (whether or not they had been used appropriately) was described as very difficult. PCPs cited patients’ resistance to anything other than opioids and their own concerns about harming rapport with their patients by changing prescriptions. While patients described sequencing therapies for pain treatment , PCPs often expressed frustrations with lack of [Chronic narcotic therapy] creates most of our problems in life, in terms of satisfaction with how we work, stuff like that. But you really don’t have many other options, really. […] [Patients are] not really satisfied. Because narcotics just really don’t work. I mean, they work for a while and then they don’t. And then you spend all your time arguing about whether they can have more or not […] Of my top 10 most difficult patients, probably seven of them are people that I just kind of spend my time sort of wrangling about their medications, because I’m trying to keep them safe. And it’s not really their fault. They’re just trying to feel better. And there’s, you know…we can’t get to that place where they feel better and I’m satisfied. [PCP 14]Barriers to more comprehensive and effective treatment, coupled with the immediacy and suffering associated with acute pain exacerbations, sometimes left medications as the only apparent option. One PCP articulated the conundrum this way:While PCPs often described patients’ resistance to moving off opioids, this resistance might have less to do with problematic attachment to medications or passive orientations to their role in treatment and more with resistance to experiencing debilitating pain. As one patient explained: “We don’t want to take a pill. We want relief.” [PT 8–4][Acupuncture] helps me to be me. Doing drugs, I’m not the same person. […] Since seeing an acupuncturist [for last 5 months] I’m completely off every medication I’ve ever been on. [PT 2–9]I actually had an appointment [with the pain clinic] and was waiting for months. But in the meantime, I had started acupuncture. And so by the time I was seen, I actually didn’t need any additional pain increase meds or anything. [PT 48–6]At several points in patients’ pain and treatment courses, A/C care options are available. In the health plan, medical necessity criteria allow for acupuncture referral for chronic pain conditions, while chiropractic care can be approved for acute, non-radicular back and neck pain. An acute flare of a chronic back or neck condition can be considered an appropriate indication for chiropractic referral by this guideline. PCPs, patients, and chiropractors and acupuncturists all described the potential for A/C care to help reduce and/or replace opioid use. Patients reported:I’ve seen so many of my patients who really get relief from nothing else, get decent relief from [acupuncture]. […] You see a patient [after they’ve had acupuncture] and they look better. They look relaxed. You don’t see the little furrow between the brows […] they can say to you, oh well, yeah, I have better range of motion. But it’s more than just that. It’s just a sense of, ‘I feel better.’ [PCP 22]I would be more likely to support and refer [to acupuncture], than to use even some of our most long-standing meds that we’ve used every day in a patient for years. […] it’s that weighing of, what are my options that are relatively safe for this patient? [PCP 20]While PCPs said:When it works with people, it's so nice because they’re not consumed by thinking about their pain. […] it’s great when you get a patient and it lasts a week. You know that they’re getting better at that point. […] It kind of gives them a break to think about something besides the pain. […] When [patients] can stop taking so much medication and have an experience of success with the acupuncture, a number of them are quite elated. Like less Vicodin, you know. [AC 43]However, acupuncturists and chiropractors perceived somewhat different potential impacts of opioid use, patients’ experience, and complicating factors.It took [the acupuncturist] about seven times and it took the pain away. [PT 9–1]I’m not having that stabbing pain, which I get in my back and in my left hip. And so, you know, then I can go for periods of time where there’s almost no pain. And as long as I go [to the acupuncturist] twice a week that seems to be enough to keep the pain at bay. [PT 30]I think they fall into kind of two camps. There’s the ones that I went once or twice. And maybe it helped, Doc. I don’t know. But I still hurt. And so there’s kind of a…And then, you know, there’s some that were like, wow, it really helps me. [PCP 7]I’ll have somebody with chronic pain on a ton of narcotics, VERY excited about their first couple of sessions [of acupuncture] and then they just sort of stop going back. And I’m like, well, you know, why did you stop going back? It seemed like it was…Well, it just stopped working. So the bloom is off the rose, kind of thing. [PCP 10]I’ve had this thought, especially with tendonitis and plantar fasciitis. I thought to myself, if the doctor had referred them more quickly to acupuncture, it wouldn’t have gone on for so long and they wouldn’t be on the bunch of pain medication that they were on. […] Sometimes those patients that come in are on so many narcotics and have had a number of steroid shots […] So if feels sort of like a drop in the bucket, you know. Like if you could really have them and work with them, over time, you probably could help them to feel better. [AC 43]Across groups, while participants described a range of positive experiences with acupuncture, it took time for patients to experience relief, if there was any relief at all. From all groups we heard acupuncture appraised in terms of time:The only thing that ever really helped me was the morphine that I’m on now. I mean, enough, you know, to function. […] The acupuncture, if I’d have done it longer maybe, but we couldn’t afford to keep doing it. [PT 1–1][acupuncture] alleviated the pain. […] I’ve had no negative experience with acupuncture. But I haven’t done it long term for a chronic pain. […] I take pain pills everyday. So, if I have to… Or, if I have the opportunity to go to acupuncture, say a few times a week in hopes that that might help, I would do it [PT 11–8]I have not ever had acupuncture replace morphine […] people want to do other things, and so they’ll use [acupuncture] with the hope of having to use fewer pain medications. But it never completely replaces that. [PCP 10]There is an occasional dramatic benefit, but more often transient benefit, and more often no benefit. Patients say, ‘Yeah, I feel better for a day doc, but there was no overall improvement from week to week.’ [PCP 4]So the elders will be on a ton of meds. And, you know, there’s only so much you can do. It’s side effects on top of side effects on top of side effects. [AC 46]There’s some cases I couldn’t help, you know, maybe five percent. No more then 10. […] those cases, usually, they are very challenging regardless of who’s treating them, or regardless of what medicine they take. They’ve already gone through a lot in the past. [AC 44]The temporariness of the effects and the possible need for follow-up acupuncture sessions often resulted in mixed or uncertain reports of the modality’s effectiveness. All groups believed that acupuncture was a relatively benign therapy that often helped patients experience short-term (at least) pain relief. No one within our sample mentioned adverse effects. The descriptions of their experiences provided information on how acupuncture was used in conjunction with or in place of opioids. However, patients, PCPs, and acupuncturists alike agreed that the result was less satisfactory when patients undergoing acupuncture are already far down the treatment path . All groups commented about situations when acupuncture was not a complete solution to CMP.When I had the acute pain, when I had that sciatica, [chiropractic] was a lifesaver. It really did make a difference. And I was able to get off of oxycodone and go back to work. [PT 3–1]Three visits [with the chiropractor] and things were much better. And I could bend and walk, better than taking a pill. [PT 28][Patients report outcomes from chiropractic care including] resolution of pain, or significant improvement of pain. Improvement in mobility. So, ability to move around and do the work that they need to do. You know, along with those things comes this feeling of hope. Like, okay, they fixed something. [PCP 1] They’re able to go back to work. They’re able to be more mobile. And they don’t need pain medicines for acute pain anymore. [PCP 17][The patients] have tried physical therapy. They’ve tried pain management. Nothing has really worked. The docs don’t know what to do. Send them over there. Here, go see a chiropractor. Whether they’re allowed to give our name or what, or it just happens, I’m not sure. But we get a lot of those people. And with them, usually six to 12 visits, we have those people not only feeling better, but back to work. [CH 45]Typical chronic pain patients will feel immediately better. And occasionally they’ll feel worse. But most of the time they feel better. And I think that surprises them, because they’ve been in this state for so long. […] It’s just changing things up so that their system is starting to work for them a little bit differently. And once that starts happening, blood flows better, circulation is better, attitude is better, mechanics are better. It just starts to work. [CH 48]Comments relating to chiropractic care were also mixed but addressed a slightly different set of issues. Many described the positive ways chiropractic care could impact chronic pain:We do what I call a series of successive approximations. […] They can walk out of here after their first twelve visits or so and go, yeah, I feel pretty good. See ya later. And then they’re back again, and we go through the process over and over and over and over again. [CH 52]I will often give chronic people anywhere from four to eight treatments, over the course of two months. And then, once every month or two, or once every quarter is a really good approach, in my opinion. [CH 50]As with the experiences described for acupuncture, the patients, PCPs, and chiropractors mentioned the difficulties they encountered maintaining effects. Chiropractors emphasized a successive treatment plan that tapered in frequency.Within less than three months [of seeing the chiropractor] the pain was gone. […] I maybe go three or four times a year. And initially, when he was taking care this, it took more than that. [PT 4–10]When [the health plan] said limited amount [of chiropractor visits], I thought, okay. I probably don’t need six weeks, or whatever, twice a week. I just want them to crack it and get me on my way. [Chuckles] Yeah, just I thought it was going to be one-shot deal. And, it wasn’t. [PT 39]I think that the benefits from chiropractic are extremely transient. Right? And I’m not really sure…I haven’t had any chiropractic training […] But I don’t think I’ve seen any studies that shows lasting benefit from it. I think the manipulations they do feel as good as cracking any joint. You may get some reflex muscle relaxation, and it’s extremely transient. [PCP 12]Periodic maintenance visits served, in part, to help correct for existing lifestyle or other complicating factors  that could erode the benefits experienced early in treatment. By contrast, patients and PCPs frequently focused on shorter duration effects.It took me six different chiropractors until I found a chiropractor that I could actually get relief from. [PT 9–4]He cracked my neck. And, I immediately knew something was wrong. I wanted to throw up. I thought I was going to pass out. And I had a really bad headache… And it lasted all night long. [PT 49-X]Occasionally, you hear from someone that the pain is worse (after seeing a chiropractor). I won’t go see him again. He was too rough for me. [PCP 15]I’ve had a couple (patients say) that they said they felt worse the day after, you know. But then they get better. Or they felt worse, just in general. [PCP 4]While all groups discussed the transience of pain relief for some patients, that evaluation differed based on whether relief was expected to be long lasting. As with the discussions of acupuncture, when expectations and experience were at odds, this could raise concerns about the quality and efficacy of the received treatment. Unlike with acupuncture, patients and PCPs were more concerned about the quality of chiropractic care patients received, the potential risks posed by adjustments, and the importance of finding the right practitioner.Right now I’m to a point where I’ll take the occasional Tylenol or Advil, you know, to make it through. But if it’s bad enough, I’ll call my chiropractor. […] I’ve also learned to live with pain too. I’ve learned to know what pain is bad enough that you have to do something. [PT 10–1]I don’t know if I would go back to a chiropractor. […] The exercises [the chiropractor] gave me still help out a lot. And the [chiropractor] I talked to said, my whole hope is that you won’t really need me anymore. You won’t need to necessarily keep coming back. But you will need other treatments, acupuncture, massage. [PT 3–2]I’ve had a lot of people say it seemed to help, for awhile. But, most often it doesn’t seem to really create any long-lasting benefit for them. I mean, for people that are clearly on a path of going from injured to getting better, they seem to do a little better through time. [PCP 14]I would say the ones that end up going, if they get a good one, they really like it. It helps them. Because I think the really good chiropractors also do a lot of physical therapy and ultrasound. And they do a lot of manipulations and good myofascial bodywork for the patient as well. So, I mean, just straight up cracking somebody, I think that’s not going to have as good long-term results. [PCP 17]I think [chiropractic is] a very appropriate approach to chronic care […] especially if chiropractor emphasizes, you know, exercise, things that the patient can do themselves and not such a passive approach, so the patient doesn’t depend on me to feel better. So you can kind of train somebody to move and keep the restoration of motion going, based on what they do on a daily basis. [CH 50]I tend to be not at all aggressive with my treatment plans. That goes back to giving people home exercises and stretching, and things like that we talked about prior. Oftentimes, if you have willing people who are willing and capable to do those things, they can get more benefit out of that. [CH 45]As with acupuncture, however, chiropractic alone was not adequate for pain management.Many patients expressed dissatisfaction with the lack of alternatives offered for pain management and frequently discussed how they used over-the-counter and prescription medications to cope with pain and to function in everyday life (even if in a limited fashion). The patients also noted fears of becoming addicted or being perceived as addicted to opioid medications. For some, A/C treatment offered a possible solution to this concern. One patient said: “If I was going to get addicted to anything I’d want it to be going to the chiropractor. It seems a lot healthier to me.” [PT 3–4]I said [to my doctor], I don’t want pain pills. I want to find out why I’m having trouble. I want to get to the root of the problem, and I want to get rid of this pain. And that was the first time that I asked him to see an acupuncturist. [PT 2–1]Both patients and PCPs reported that a patient’s desire for non-pharmacological options could help encourage referral to A/C practitioners. As one patient described:There are patients who really hate drugs. They hate the concept of taking any kind of medication. And so they’re more likely to be open to [acupuncture], and to value it more just for the sole reason that it doesn’t involve taking a medication. [PCP 1]This description aligns with what many PCPs told us. For example, a PCP said:[Patients using a narcotic drug are] challenging because of the difficulties in separating out issues of dependence versus addiction versus legitimate management of pain. And plus the economic pressures and stuff. And then the issues of abuse and diversion, it’s just like, my God, this is sixteen layers and all I really want to do is treat their pain. [PCP 9]Mirroring the challenges described by patients, many PCPs expressed frustration with the complexity of treating patients on opioids. As one PCP said:We get our little ten-minute per patient, which is so grossly, woefully inadequate amount of time to see a patient. Ten minutes, right, for all your problems. And so nobody wants to take the time to explore things other than drugs for people with chronic pain. [PCP 17]PCPs continually emphasized problems at the patient level , but also frequently mentioned (but ultimately downplayed) other historical and structural barriers to better pain management . Despite this, many patients indicated that all they were offered in clinic visits was more medications to manage their pain. Short office visit times likely limit PCP-patient discussions about self-care and facilitate the maintenance of narcotic agents as the ultimate default treatment. As one PCP noted:I have to know what the side effects are. And are the side effects why the patient is in here? And therefore, I really can’t do a whole lot about that, other than get them out of some pain. But as long as they’re taking the medication, the joint pain is always going to be there. [CH 48]Almost all PCPs stated that A/C care was not a first-line treatment, so they often would not make referrals to A/C care until the patient had already tried (and failed) several other lines of treatment. Several acupuncturists and chiropractors noted that by the time they saw patients, however, they were already medicated and in a more complicated state than they might otherwise have been if they had been referred earlier in their pain trajectory. As one chiropractor said:The complicated nature of the patients they were seeing, limitations on the number of A/C visits allowed under the referral, and lack of coverage for maintenance therapy created challenges to the outcomes that might be realized.The incongruence in timing of, expectations for, and plan coverage of A/C treatments were explicit and implicit themes throughout participants’ descriptions of their A/C experiences. Appraisals of and concerns about the modalities sometimes differed, but they contributed to at least some of the frustrations about pain management and the use of opioid medications.We used qualitative data to explore patient and provider experiences with alternative approaches to opioid pain management. Based on the results presented above, we suggest a new model for thinking about chronic pain. The CMP patient, PCP, and A/C provider narratives illuminate the multifaceted problems and frustrations all three groups face in managing chronic pain. Figure Our analyses revealed an array of participant views, impacted by not only PCPs and A/C providers, but also by social context and health policy considerations. While this context is often taken for granted in the research literature, our participant groups described how this occurred locally and provided a specific context for their experiences managing chronic pain. Interview and focus group data uncovered widespread dissatisfaction with opioids among PCPs, patients, and A/C providers. Consistent with this finding, systemic interventions have been implemented at the health plan over the past five to seven years in an effort to stem the tide of opioid misuse. Patients using chronic opioids are now required to sign opioid therapy plans and to submit to periodic urine drug screening. Brief pain assessments are periodically administered to all these patients and the results stored in the electronic medical record. Patients whose daily morphine equivalent intake exceeds set safety limits are being targeted for aggressive tapering, and a dedicated team of pain management pharmacists has been deployed in the primary care clinics to support primary care teams in these efforts. Despite these efforts, however, PCPs expressed dissatisfaction with medication for pain management  and raiThere were a range of views as to the appropriate role of A/C care in this context. Those patients who experienced pain relief after A/C treatment indicated that they were no longer debilitated by pain and could engage more fully in recommended lifestyle changes, without the side effects of and long-term dependence on opioids. The lack of coverage for non-acute, maintenance A/C care meant that the ability of A/C to successfully assist patients in managing pain and medication step down may not have been fully realized, though we currently lack the evidence base to guide A/C “maintenance” therapy. Interestingly, Eaves and colleagues  found thOur findings also showed that patients and providers were not always satisfied with the overall effectiveness of A/C treatment. Some of these appraisals were associated with expectations about the timing or duration of relief (sometimes reported as immediate but not long lasting). The number of authorized visits for A/C care was perceived as too few and they occurred over too brief a time span. Suspicion of unfamiliar medical systems and unknown providers was an additional obstacle. There were suggestions in these data that clinical improvements with A/C were less impressive for patients with longer duration of pain and/or who were heavily medicated. These issues require further study.These findings may also point to a need to better educate both patients and providers about results they can expect in terms of sequencing, time frames, and impacts from A/C treatment, and to a need to tailor treatment benefit structures to these realities. In some cases, patient expectations may be unrealistic. For many patients with long-standing pain, for example, complete elimination of pain will not be possible. Instead, these patients must focus on improving function and quality of life rather than on eliminating pain. Randomized trials suggest that A/C care provides the greatest short-term benefits while the long-term sustainability without continuing treatment is less clear . UnfortuAt the same time, randomized trials suggest that A/C care may have overall efficacy at least as good as conventional medicine , 49 thatInterestingly, patients and PCPs articulated different perspectives of what happened during the clinical encounter, particularly about which group pushed for medications and which opened up possibilities for non-pharmacological alternatives. Patients indicated that while they were concerned about and resistant to initiating opioids due to possible side effects, addiction, and stigma, many had experienced opioids as the only thing that could reduce their pain. Thus, they wanted opioids when experiencing an acute flare and desiring relief and in the absence of other positive treatment experiences. Other researchers have reported similar findings , 53. Whihad or had not used the acupuncture or chiropractic benefit through the health plan, we found that across all groups, patients had experiences, at various points and through various means, with acupuncture and/or chiropractic care to treat their pain and other conditions. This factor sometimes made analyzing their experiences by modality difficult. Third, our A/C provider samples were limited to those who received many referrals from the health plan. Having a wider set of acupuncturists and chiropractors, including those not contracted with the health plan, might have provided different perspectives on the treatment of patients with chronic pain and the use of opioid medications. Finally, our codebook was mostly created through deductive processes, whereas the material presented here was largely captured through identification of themes within code reports. Using a more inductive coding approach, such as Grounded Theory, might have allowed for a closer and more systematic reading of our data.Our analysis has several limitations. First, we did not specifically ask participants about opioid medications. A more targeted question-and-answer session could have helped us distinguish nuanced and differing ways patients think and feel about pain medications as a broad class of over-the-counter and prescription medications, and about opioid medications specifically e.g., , 54). In. In54]).Our study identified dissatisfaction with using opioids for long-term chronic pain management and the many practical barriers that challenged access to other options from the perspectives of CMP patients, PCPs, and A/C providers. While there was variation among our samples’ experiences with and perspectives of A/C treatment, most of our participants perceived A/C care as helpful in providing short-term pain relief. However, incongruences in timing of, expectations for, and plan coverage of A/C treatments were issues that seemed to limit that potential relief. Our data pointed to the complexity of chronic pain management, particularly given the typical duration of ongoing pain management needs, and the potential benefit for additional study to identify ways to better support clinical decision-making. Finding the best long-term treatment strategies will likely vary depending on the unique patient’s condition, treatment trajectory, expectations, lifestyle, individual values, benefits coverage, and availability of services. While experiences and perceptions of acupuncture and chiropractic care differed along several dimensions, improving access to them would offer providers and patients more options in addressing this complex problem.Each patient is unique and the persistent theme of the importance of timing in our data point to the complexity of treating individual patients. Finding the best treatment for an individual may depend on his or her condition, where he or she is in his treatment trajectory, and the expectations, lifestyle, individual values, benefits coverage, and availability of services. Moreover, patients typically come in to see their physicians when they are in pain. As our sample exemplified, patients were trying many different things and used A/C care according to their experiences and perceptions of both their pain and the utility and accessibility of different treatments. There is no one best approach, and deciding on which therapies to use and when will depend on many factors in the context of chronic pain management.


ISRCTN97157037.Diosmin has been widely used to treat patients with vascular pain for its potent anti-inflammatory and analgesic effects. To evaluate the therapeutic effects of Diosmin in the treatment of radicular pain, we conducted an investigator-initiated, randomized, active-controlled noninferiority trial between January 1, 2009, and December 1, 2010. Diosmin (50 mg/kg/day) was orally administered to treat the radicular pain in 150 patients for one month. Another 150 patients with the same symptom were given 20% 250 ml mannitol (1 g/kg/day) for 7 days and dexamethasone (10 mg/day) for 3 days intravenously guttae. Short-term relief and long-term relief were measured. Secondary outcomes include improvement in functional and psychological status, return to work, and reduction in anti-inflammatory analgesic drugs intake. Patients treated with oral Diosmin achieved reduction in radicular pain. The total satisfaction rate of Diosmin group was 84.7% , and the complete satisfaction rate was 50.7% . No statistically significant difference was found between the Diosmin group and the active-control group regarding patient satisfaction. No adverse effects were found during the study period. Our study suggests that clinical application of Diosmin with a dose of 50 mg/kg/day might reduce the radicular pain. This trial is registered with  Radicular pain is a common chronic pain, which is commonly caused by disc herniation, although a space occupying lesion in the lumbosacral spine or spondylolisthesis can also result in such clinical condition. The main cause of lumbosacral radiculopathy is intervertebral disc herniation. Among patients with lumbosacral radiculopathy, about 10–15% had surgery eventually, but overall the majority recovers with conservative management. In general, nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are commonly used to treat inflammatory pain in clinical practices [Studies suggest that the mechanism of radicular pain is due to the inflammatory nerve roots . ChemicaDrug therapy, physical therapy, and psychotherapy, surgery, bed rest, acupuncture, spinal cord stimulation, cryotherapy, and radiofrequency thermocoagulation have been used for treating radicular pain . For morAnti-inflammatory cytokine therapy may be an effective treatment of sciatica which resulted from disc herniation due to its capability of preventing the dorsal root ganglion compartment syndrome, which might be a side effect of applying nucleus pulpous topically. Flavonoids, a group of plant extracts, have been widely used in biochemistry and pharmacology because of their anti-inflammatory, immunomodulatory, and antioxidant effects in vivo and in vitro . FlavonoAlthough Diosmin has been widely used in treating various pains for patients with intravenous vascular pain, to the best of our knowledge, there is no published data so far for the indication of radicular pain. We compared the degree of pain relief and physical function improvement in the radicular pain patients treated by Diosmin and an active treatment in the presented study.ISRCTN97157037) “(http://www.isrctn.com/ISRCTN97157037)”.This investigator-initiated, randomized, active-controlled, noninferiority trial was carried out in the Department of Orthopedic Surgery, Drum Tower Hospital of Nanjing University Medical School between January 1, 2009, and December 1, 2010. The protocol was approved by the Ethics Committees of Drum Tower Hospital of Nanjing University Medical School. Three hundred consecutive outpatients with radicular pain  [The inclusion criteria were preliminarily diagnosis of radicular pain; age ≥ 18 years; pain duration ≥ 30 days; being previously treated with nonsteroidal anti-inflammatory drugs, opioid medications, or physical therapy without pain relief for more than one month; being with normal or slight decrease in the height of disc space on lateral plain X-ray film; and being initially considered eligible for surgical intervention.Based on patient's history and clinical and imaging examinations, the exclusion criteria were patients with spondylolysis, lumbar canal stenosis, isthmic or degenerative spondylolisthesis, inflammatory arthritis, spinal instability, infection, previous lumbar surgery, neurologic disease, tumor, or psychological disorders (such as depression or using antidepressants or anxiolytic medications). Patients with lumbar intervertebral disc protrusion who were diagnosed according to magnetic resonance by a radiologist and an orthopedic surgeon and needed surgery were also excluded.Three hundred outpatients with radicular pain were randomly assigned into the Diosmin group and the active-control, that is, mannitol and dexamethasone , group wShort-Term Outcomes. A visual analog scale (VAS) was used to measure the main outcomes [outcomes . To measoutcomes , with pooutcomes  was fillLong-Term Outcomes. The patients had regular visit to the outpatient department of the hospital or we took regular telephone follow-up for those who did not have regular visit. Current pain level and satisfaction were recorded during each visit or follow-up for every patient. The long-term outcomes were evaluated in the 24th month after randomization by hospital visit or telephone interview. Medication usage and posttreatment satisfaction were examined. Usage of NSAIDs or opioid medications was graded as follows: 1, never; 2, occasional; 3, regular. A three-grade scale was used to rate patient's satisfaction: 1, completely satisfied ; 2, satisfied (slight pain that requires no medication and mild restriction of activities); 3, unsatisfied (moderate to severe pain that requires medication and moderate to severe restriction of activities) [ivities) .Adverse Effect. Adverse effects, including gastrointestinal discomfort, were recorded in adverse effects form through patients' complaint during outpatient department visit or follow-up.To minimize investigator bias, the independent investigator who recorded all the results was blinded to both therapeutic groups.t-test and χ2 test were used for statistical comparisons for continuous variables and categorical variables, respectively. VAS, NRS, and RM-Q scores of pretreatment and posttreatment at different time points were presented as means with corresponding 95% confidence intervals (CIs) and compared using two-way analysis of variance. Two-sided P values < 0.05 and one-sided P values < 0.025 were considered statistically significant for baseline comparison and for posttreatment comparison, respectively. Statistical software programmes IBM SPSS 24  and Stata 14.2  were used for all the analyses.Intention-to-treat analysis was used to avoid various misleading artifacts that could arise in the trial such as nonrandom attrition of the patients. Missing values were imputed by the last-observation-carried-forward method as recommended . All resn = 150) and the active-control group (n = 150). The baseline characteristics were balanced between the two groups and no statistically significant difference was found  in the Diosmin group and the active-control group, respectively. The courses of treatment are 4 ± 1.4 months and 4 ± 1.5 months  in the Diosmin and the active-control group, respectively. Duration of pain ranged from 1 month to 48 months and there was no statistically significant difference between two groups . The level of lesion and baselines pain score for both groups are shown in t = 2.093, P = 0.037; In total, 300 patients with radicular pain were included in the study and were randomly assigned into the Diosmin group  after treatment decreased notably in both groups (data not shown). Again, no statistically significant difference was found between the two groups .There was no serious adverse effect in both groups. Five patients in the control group reported mild nausea without vomiting. The symptoms disappeared after drug withdrawal and no special treatment was required.A significant proportion of patients suffering from chronic pain with radicular component have a high disability index , 18. StuReports showed that conservative treatment for radicular pain had satisfactory results. Besides treating medical and psychiatric comorbidities, conservative treatments include physiotherapy, meditation, transcutaneous electrical nerve stimulation, and relaxation techniques, activity, exercise, and/or stretching to reduce spinal extension . Althougα, and nitric oxide (NO) have also been identified around and within intervertebral disk tissue. The evidence indicates that inflammatory factors TNF-α as well as NO, prostaglandin E2 (PGE2), and IL-6 are the main candidates among substances potentially responsible for nerve root pain according to the current pathophysiology [From chemical aspect, experimental studies have shown the spontaneous resorption of disk herniation  and the ysiology –38. The ysiology .Our study indicates that patients treated orally with Diosmin achieved reduction in radicular pain, as measured by the NRS, RM-Q, and VAS. The satisfaction rates of the patients were 84.7%  and 84.0%  after 24 months of randomization for the Diosmin group and the active-control group, respectively. In general, all primary outcomes were similar between the Diosmin group and the control group without statistical significance. No serious adverse effects were found in both groups. However five patients in the control group reported mild nausea and the symptoms get disappeared after drug withdrawal and no special intervention was required.Improved venous tone and capillary bed microcirculation, reduced capillary permeability, increased lymphatic drainage, and inhibited inflammatory reactions have been identified as main mechanisms of Diosmin's action . Being pAlthough our study provided evidence that Diosmin may have similar pain relief effect compared with the active-control treatment mannitol plus dexamethasone, we have to acknowledge that our study was a single center trial and limited by the small number of patients. Further multicenter randomized controlled clinical trial with larger sample size is required to confirm the clinical application of Diosmin in treating radicular pain.As a potential promising therapeutic drug, Diosmin may reduce radicular pain that might partly be attributed to its anti-inflammatory and analgesic components. Its effects are similar to currently used active treatment mannitol plus dexamethasone.