Additional interviews were conducted with their physicians (n = 7) to obtain physician perceptions on discontinuation and to expand understanding of the patients' experiences. Aspects of patients' pain and medical care through the discontinuation process revealed emergent themes that both converge and diverge from that of treating physicians. Areas of divergence include the motive for discontinuation, which was condemned by most patients but supported by all physicians, and the perceived impact of discontinuance on pain control, with the majority of patients experiencing a negative impact and most physicians describing it as insignificant. Perceptions of patients and physicians coincided on the need to optimize pain management practices.OxyContin, formerly one of the most commonly prescribed medications for chronic pain in Canada, was discontinued, delisted from the Ontario Drug Formulary, and replaced by a tamper-resistant formulation in 2012. The impact of discontinuing OxyContin on patients formerly prescribed it to treat chronic pain was unreported. Patients with chronic pain aged 45 years and over ( OxyContin, a controlled-release semisynthetic formulation of oxycodone, was approved by the US Food and Drug Administration in 1995 . This opOxyContin was discontinued and delisted from the Ontario Drug Benefit Formulary in early 2012 . The decComplicating the picture further, the risks of addiction associated with OxyContin and the ensuing discontinuation were frequently covered in the media while the drug's usefulness in chronic pain management remained debatable. A subsequent systematic review showed that, despite widespread use, there was insufficient evidence to suggest long-term opioids were actually effective in improving chronic pain and function . WorkingA concurrent nested mixed-methods approach was used to capture the experiences of patients with chronic pain and their physicians after OxyContin discontinuation. This study was reviewed and approved by the Office of Research Ethics at the University of Waterloo and the Health Sciences Research Ethics Board at Western University.Patients were recruited from client bases of patients who had received OxyContin for chronic pain at two rural primary care sites and one urban specialty pain clinic in Southwestern Ontario. Recruitment posters and flyers included brief information on the research topic, study purpose, inclusion criteria, time requirements, and contact details. Eligibility criteria included being 45 years or older, suffering from chronic pain for at least six consecutive months, and having taken OxyContin for at least six months before discontinuation. Eligibility was determined by telephone screening. The age of 45 years was selected as a cut-off to target people middle-aged and older since the prevalence of chronic pain increases with age –24.Names of respective physicians responsible for OxyContin prescribing were collected from study patients. The physicians were contacted by the research team, informed about the study, and invited to participate.All participants were assigned random code identifiers to maintain confidentiality.Data were collected between July and October 2013. Study interviews were held either in a private clinic room or at home for participating patients and at the clinic for participating physicians. Before interviews, patients completed two questionnaires—the Patient Treatment Satisfaction Scale (PTSS) and the Brief Pain Inventory (BPI)—to provide point-in-time insights into measures such as pain intensity, satisfaction with current pain medication, and effect of pain on their quality of life (QOL).The PTSS, used to evaluate satisfaction with pain treatment, is comprised of 39 items assembled in five domains: (a) information about pain and its treatment (five items); (b) medical care (eight items); (c) impact of current pain medication (eight items); (d) side effects of current pain medication (12 items); and (e) satisfaction with current pain medication [divided into medication characteristics (three items) and efficacy (three items)] to be evaluated on a five-point Likert scale .The BPI, applicable to pain of different etiologies , 27, incPatient interviews took about 40–60 minutes and physician interviews took about 20–30 minutes. Each followed a guide covering the discontinuation process, pain relief, and personal experiences. Physician participants were not informed of any information relevant to the patient participant and interviews focused on their general perceptions instead of specific cases. All interviews were conducted by an investigator who was a graduate student in pharmacy with training in qualitative research.Quantitative survey data were analyzed using Qualtrics, an online survey analysis application.The audio recordings of each interview were transcribed manually and proofread by a second reader and then sent to participants for review. Data from the interviews and personal observations were sorted and manually coded for units of meaning using a two-step process, where an initial four-to-five-word code was assigned to each line of the transcript to reflect the meaning of the line. These codes were reviewed repeatedly to elucidate specific focused codes and to synthesize theoretical categories representing distinct patterns and themes. The data sets were compared and contrasted to identify similarities and differences. Memo-writing, both field notes made during the interview and reflexive memos written during the coding and categorizing of data, was employed to capture reflections on the collected data. The themes that emerged were then categorized into focused classes. Analysis and theme categorization were confirmed by a second reader with Ph.D. training in qualitative research.A total of six patients enrolled from the urban specialty clinic and seven enrolled from the two rural primary care sites . Participant characteristics are summarized in All patients provided their physician's contact information, resulting in communications with eight physicians  and three pain specialists) at three locations. All physicians enrolled in the study, but one GP withdrew, leaving one patient unrepresented.The PTSS revealed that eight (61.5%) patients received sufficient information on causes of their pain and treatment options, seven (53.8%) required more information on their pain medications, and ten (76.9%) wished to be more informed on possible side effects. None wanted to receive less information on any aspect. Twelve patients (92.3%) noted that they questioned their physicians easily, eleven (84.6%) agreed that medical staff kept them from worrying, and ten (76.9%) confirmed their physicians' willingness to prescribe desired medications. Patients were divided on their opinions of the impact of their medication on their QOL, with equal numbers agreeing or disagreeing that their medication improves concentration or permits increased participation in leisure activities. However, eight patients (61.5%) agreed that their medication positively affected their physical health and improved their outlook on life but nonetheless failed to meet expectations, while nine (69.2%) were dissatisfied with their current medications. Only three (23%) patients were satisfied with their medications, and one (8%) was neutral.n = 13), with average pain at 5.2 (range: 1–8), which was relieved 53.8% (range: 10–90%) in the past 24 hours. Pain interfered most with sleep, normal work, and enjoyment of life, but other QOL domains were also negatively influenced by pain. Appetite was the only domain where some patients reported no interference.The six major themes and their contributing subthemes that emerged are described below and listed in That kinda got me mad, cause I thought well you know…they're taking it off the market because of people abusing it…It's not fair to us, you know. … I think the government was wrong to… pull them off the market, you know, because of people abusing them, no like they weren't looking at the people that need them…But I think it's really unfair that people that really do need them can't get them. Furthermore, patient participants felt neglected and inadequately considered in the decision to discontinue the drug. Some patients put blame on prescribers who prescribed opioids unprofessionally or too easily, thus contributing to the misuse problem. Others expressed uncertainty of the expertise of GPs in prescribing opioids such as OxyContin. Patients also condemned the approval and introduction of generic forms of OxyContin.Overall, patients strongly disagreed with the rationale for discontinuing OxyContin to reduce addiction. In contrast, patients strongly believed that discontinuation would fail to halt OxyContin addiction because people could instead abuse other medications, succeed in overcoming the tamper-resistant mechanism of the new formulation, and/or access OxyContin where it was still available. Patients felt they were being punished for the actions of people who misuse the medication and were concerned about being perceived as being dependent themselves. They also feared removing OxyContin would lead to increased emergency visits because of withdrawal, as well as increased pharmacy robberies and higher crime rates.I just found it just wasn't working for me…I went to the doctor and I talked to him and I said, look, I don't think this is working so…he just never filled out no more, no more prescriptions for me, cause if it's not working, why take it?…Um…I found the OxyContin worked so much faster where the other, I don't know, it just didn't, it just didn't cut the pain. I don't know why the difference was, if they were the same pill and that, but it just wouldn't, I didn't find like I was getting the relief out of it like I did the others. Other medications patients tried also failed to match the pain relief experienced with OxyContin and negatively impacted physical activity and cognitive ability. As a result, patients felt threatened by the discontinuation and deprived of their medication and resented enduring trials to optimize alternate medication regimes. Some experienced withdrawal while switching to other medications and preferred to continue with OxyContin, which they felt provided optimal benefit. Two patients resented having to pay for OxyNEO, which was not funded as a general benefit under the Ontario drug benefit program once the initial year ended.I was very upset. That's what I was. People who worked and had insurance companies that would pay for it can continue it. We are the lower part of the income scale. My option is OxyNEO, but I have to pay for it. I have no idea how much it is and if I have to pay for my occupational therapy, if I have to pay for my, what's its name to come and do my exercises, if I have to pay for, I mean this country that pays for your medication is not telling the truth.  While all thirteen patients reported successful pain management with OxyContin, eight were dissatisfied with OxyNEO, saying it provided reduced pain relief. OxyNEO was also felt to be slower in onset of action and more difficult to swallow.It hasn't affected me at all. In other words, I wouldn't know, uh, whether I am, by the way I feel, I can't tell, I wouldn't be able to tell whether I am still taking OxyContin, if I was in a blind taste test, not taste test but uh, blind medication administration test I suppose. Those with good pain control to begin with described a more smooth transition to OxyNEO (n = 2) or hydromorphone (n = 1). Both patients that experienced residual pain with OxyContin continued to have similar pain with OxyNEO.Five patients were unaffected by discontinuation, three received satisfactory pain control with their alternate medication, and two experienced similar residual pain while taking OxyContin.I realized that it was an addiction and I couldn't, I realized how I felt if I couldn't get to it…so I knew it was an addiction, and I knew I had to get off of them because that's not, my plan of life to live on addiction…so I decided that's it, I'm gonna do it on my own and I did. Some other patients indicated their desire to discontinue opioids at some point in their lives, disliking the idea of lifelong reliance on a medication. Many expressed a fear of addiction but also feared withdrawal symptoms and intolerable pain from suspending use of opioids.Two patients decided to discontinue OxyContin by themselves because of concerns over becoming physically and psychologically dependent on it. Both suffered withdrawal symptoms and uncontrolled pain, diminishing their level of activity.I just found different ways to cope with it, and to, I guess accept that, it's here to stay, and um, you just have to kind of figure out a way to, um, to try manage it and try, still have a bit of a life too…I guess the change just has to come from you just trying I mean myself just trying to, um, find a way through it or work around it. Most participants felt the need to make additional pain medications available to chronic pain sufferers, as they had exhausted alternative medications and therapies. Participants voiced hopes for better alternatives and wished for the return of OxyContin.Seven patients' hopes for attaining optimally managed pain changed over time, replaced with an understanding that they will live with some degree of uncontrolled pain.The OxyNEOs…the doctor didn't even know side effects of it, the pharmacist told me side effects of it, the doctor didn't know. It's like she, here's a prescription, but I do not know nothing about it. No, no, nobody said anything. Well, I asked my doctor and only because I heard on the news, she didn't come to me and tell me this was gonna happen, it was all the news…I wanted to know why, and um, I have to think, because I was very concerned, um, because at the time when I listened, when I heard it on the news, they were, they wanted to take it right off the market, that's what I was concerned about…I was worried what's the next step…like there was a lot of thoughts, uh, like that that was going through my mind. Some patients recalled being put on OxyContin without receiving any information on the drug properties and its long-term effects in advance. One patient expressed a lack of trust in the medication-related information provided by her physician at discontinuation because the physician had failed to inform her about OxyContin's properties at initiation.All thirteen patients perceived flaws in patient education, communication, and treatment in the course of discontinuing OxyContin. They learned about OxyContin's discontinuation from the media and Internet. Some reported that their physicians did not provide information on why OxyContin was discontinued or the range of alternative medications available, revealing communication gaps partially attributable to difficulty in accessing physicians. When they visited their physicians, patients were disappointed by the reaction to their clearly communicated concerns.Patients also expressed uncertainty about the risk-benefit ratio of using OxyContin or alternative medications. Decisions were based upon their personal experiences and on their physicians' advice. Conflicting opinions among physicians and poor integration of medical services across healthcare professionals led to increased confusion about the medications. Less frequently mentioned concepts included learning about inaccurate information about medications, recalling bad experiences with healthcare providers, and self-medicating according to personal needs.Seven physicians  provided insights on the discontinuation of OxyContin, which resulted in five themes, each with a number of subthemes. These are outlined in I think it was a good idea, to discontinue OxyContin, um, mainly because especially in the area where I practice we saw a lot of abuse and misuse, and still do, um, and given that there are other, you know, effective alternatives in terms of pain management, I think it was a good decision. (MD4)All physicians strongly supported the discontinuation of OxyContin and its removal from the Ontario Drug Benefits Formulary. Six supported the provincial government's decision to leave OxyNEO unfunded, thereby restricting accessibility through the Exceptional Access Program. They believed the addiction potential of OxyContin exceeded that of other opioids, resulting in elevated rates of misuse.I don't really think I had any problems at all with my patients going from OxyContin to OxyNEO. (MD6)It didn't seem like a big blip or anything in my practice, it just, patients were explained, they changed over and the pain was controlled, so it was not a big issue. (MD5)Some seized the opportunity to switch patients to other medications because of their specific dislike of OxyContin. Two physicians perceived an association between unsatisfactory outcomes to illegitimate use of the medication by patients and expressed concerns for patients who found switching to a different painkiller problematic, stating that equivalent relief should be obtained with other medications, particularly OxyNEO.All physicians believed that discontinuation of OxyContin had insignificant influence on patients' ability to attain equivalent pain relief, as other pain medications were of equivalent efficacy. They asserted that transitions were carried out efficiently with a sufficient range of treatment options.One pain specialist who saw the highest number of patients in the clinic categorized 65%–75% of patients as ones who understood the reason behind the switch and were confident with switching to non-OxyNEO alternative medications. This further supported the perception that discontinuation had an insignificant impact on pain management.I think the Canadian guidelines for safe and effective opioid prescribing, if applied uniformly, will do a lot. (MD3)Lack of adherence to the practice guidelines was thought to be the issue in prescribing. While a need to regulate opioid prescribing was not suggested, one GP mentioned the idea of a narcotic database, expecting that such an initiative would enhance monitoring strategies for opioid prescribing across the province.Six physicians deemed existing guidelines for opioid use to be adequate and sufficient for physicians to prescribe opioids safely. They felt the use of opioids across different practice settings can be optimized when physicians follow the guidelines in place, ensure appropriate prescribing, and perform accurate conversions between opioids.I'm actually very angry, what was the whole point then? What was the purpose of OxyNEO then? Right? That makes me mad…so the whole exercise about taking it off the street is actually negated if they have a generic on the market, right? (MD5)I have never used a generic controlled release and I would not recommend it…it's a mimic of, uh, of OxyContin, and carries the same risks of substance abuse. So most pain specialists were against, the, release of generic controlled release oxycodone, and we discouraged the use, uh, and I don't use it. (MD2)Physicians considered existing pain medications sufficient to replace OxyContin. All but one strongly opposed the introduction of generic products, believing that doing so would defeat the purpose of discontinuing OxyContin. No physician participant had prescribed generics to their patients and six actively discouraged their use. While they agreed generic products could be beneficial for some patients, this consideration was felt to be greatly outweighed by the negative consequences that could arise.I thought it was done quite abruptly without any warning, I guess they had to do that because if there'd been warning, it's organized and there would have been OxyContin coming across the border and stuff…many of our patients only come every three months, so there was no way we could see all those patients and discuss with them, um, and the other thing was it was going to immediately convert to exceptional access so that, um, there was a little bit of a barrier, and then the 80 milligrams would not be available and also, um, so yeah time-wise, it wasn't enough time. I understand perhaps why they did it and I understand it was the company that set that timeline, not the provincial government or the pharmacies. (MD3)In addition, physicians proposed the creation of a national database accessible by all healthcare providers to monitor patients' use of opioids and to prevent “doctor-shopping.” Some also stressed a need to provide additional training to all physicians to enhance opioid prescribing expertise.While all seven physicians successfully switched the majority of their patients off OxyContin, challenges were encountered. These included the lack of access to OxyNEO and the cost to those without drug plans, the abruptness of the discontinuation, and the short period that was allowed for physicians to switch patients to other pain medications. This pressured physicians to make conversions quickly, eliminating the possibility to wean patients gradually from OxyContin. While the rationale behind the discontinuation was considered reasonable, delays in notifying healthcare professionals about the discontinuation and in processing applications to receive OxyNEO were not. Anticipating a three-month period to process applications, physicians switched the majority of patients to other medications to avoid wait-times and withdrawal.This study explored perceptions patients with chronic pain and their physicians had on OxyContin's discontinuation and its impact on care. Both patients and physicians agreed that gaps existed in the discontinuation process that could be improved on. Compared with physicians, areas of divergence for patients included the motive for discontinuation, the impact of discontinuation on chronic pain control, and the changes necessary to improve care.Perceptions of the motivation for discontinuing OxyContin varied considerably among patients and physicians. Patients and physicians disagreed on the reason to discontinue OxyContin to address misuse and on whether phasing out the medication would fulfill this purpose. Despite doubting that restricting access to one problematic medication while leaving other opioids accessible would address the issue of addiction, physicians strongly agreed that the popularity of OxyContin among nonmedical users necessitated its discontinuation, asserting equally effective medications were available for legitimate users. In contrast, the majority of patients from this study believed that discontinuing OxyContin was wrong because it adversely affected their pain management and unfairly disadvantaged them. They had little faith that the strategy would work and held more negative beliefs regarding withdrawal and alternative treatment options. The introduction in 2010 of OxyNEO in the United States resulted in reduced abuse of OxyContin, but abuse of other long-acting opioid medications and heroin increased –30. SuchSeveral other opportunities in patient-physician communication were identified. Patients were learning about OxyContin's discontinuation from the media rather than from their physicians. Physicians perceived that they had switched the great majority of their patients to other analgesics successfully, while patients felt more negatively impacted by the switch. Such differences of opinion were not openly communicated with each other. The short time to discontinuation, discontinuation that took place while some patients were between clinic visits, and the media announcement before physicians could take the time to inform their patients likely were all contributing factors. Patients were also unhappy about their lack of involvement in the decision-making process after discontinuation. While some patients prefer to participate in developing medical plans for their illnesses and others adopt a more passive attitude , 31, it Patients stated that physicians did not provide them with enough information and felt their concerns went unheard. For example, some patients found alternative medications following discontinuation were ineffective but felt they were unable to communicate such concerns. This is consistent with previous literature that showed clinicians can underestimate patient desire for information to better understand their health condition and their need to feel known and understood . While iMost patients and all physicians in this study felt that the healthcare system could improve but focused on different aspects. Patient dissatisfaction was most commonly related to not receiving adequate information about their medication therapy, particularly helping them to better understand the benefit-risk ratio at initiation. This was further complicated by conflicting messages from different healthcare professionals and the media. A helpful strategy could include dedicated time for standardized patient education for high-risk medications such as opioids at initial prescribing and/or dispensing. Integration of the pharmacist in this role could help to alleviate physician time constraints and reinforce key messages. On the other hand, most physicians admitted that managing opioid abuse against maintaining optimum pain control for chronic pain sufferers seems unattainable and required system-wide strategies. They supported proposals to develop a national database to better monitor the use of opioids , 42, to While physicians generally expressed confidence in the ability of GPs to prescribe opioids, patients were more doubtful. A survey of Ontario primary care physicians showed that 86% felt confident with opioid prescribing but most voiced concerns over opioid use and 42% had patients who experienced opioid-related adverse events . Other rThe diverse study sample of patients and physicians is a main strength of the study. Exploring experiences of physicians in different practice settings  as well as patients residing in rural and urban communities allowed us to collect data from varied perspectives. Secondly, obtaining perceptions from both patients and physicians illuminated certain points of agreement and controversy related to the same topic.Inherent with voluntary participation, participant bias may have influenced the results. Participants with stronger opinions, whether positive or negative, may have been more likely to participate. The small sample also made the findings less generalizable to other population groups such as younger individuals with chronic pain and patients in other care settings such as long-term care. The lapse in time since discontinuation may have contributed to inaccuracies in recall. In addition, because of time and resource limitations, pharmacists were not included in the current study. Pharmacists play an important role in managing prescription opioid access and had first-hand experience in OxyContin's discontinuation.This inquiry contributes to a better understanding of the first discontinuation and reformulation of an opioid indicated for chronic pain management in Canada. Patients and physicians disagreed in their level of support for OxyContin discontinuation and in their perception of the negative impact discontinuation had on pain control. They also identified numerous inadequacies within OxyContin's discontinuation and opioid prescribing processes that formed barriers to optimum care. Comprehending the patient and physician perspectives will help healthcare professionals and decision-makers better address these gaps in care.


To evaluate the feasibility of an individualized interdisciplinary chronic pain care plan as an intervention to reduce emergency department (ED) visits and improve clinical outcomes among patients who frequented the ED with concerns related to chronic pain.  A prospective cohort design was used in an urban tertiary care hospital. As a pilot program, fourteen patients with chronic pain who frequented the ED  received a rapid interdisciplinary assessment and individualized care plan that was uploaded to an electronic medical record system (EMR) accessible to the ED and patient's primary care provider. Patients were assessed at baseline and every three months over a 12-month period. Primary outcomes were self-reported pain and function assessed using psychometrically valid scales.  Nine patients completed 12-month follow-up. Missing data and attrition were handled using multiple imputation. Patients who received the intervention reported clinically significant improvements in pain, function, ED visits, symptoms of depression, pain catastrophizing, sleep, health-related quality of life, and risk of future aberrant opioid use.  Individualized care plans uploaded to an EMR may be worth implementing in hospital EDs for high frequency visitors with chronic pain. The Pareto principle , as applMany pain complaints are nonemergent and inappropriate for the ED , 8. ThisAcute exacerbations of chronic pain can be costly , and focReviews of interventions to reduce ED visits among HFVs have reported that interdisciplinary case management and individualized care plans have modest effects with reduced ED visits and associated costs –27. Few This investigation evaluated the feasibility of an individualized interdisciplinary chronic pain care plan developed in conjunction with the hospital emergency team, primary care provider (PCP), and patient to improve pain, healthcare utilization, and clinical outcomes endorsed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) . The aimThis was a 12-month prospective cohort design. Patients were identified, underwent baseline evaluation, received intervention, and were assessed at 3-month intervals over a subsequent 12-month follow-up period. Data obtained at 12-month follow-up were compared to baseline data among the cohort.The study was conducted at a large, urban, tertiary care hospital with 172,445 patient visits per year.Patients were referred by ED physicians and screened by a member of the research team with significant experience in the management of chronic pain  to verify whether they met the following inclusion criteria: (1) over 18 years of age; (2) experienced pain that persisted longer than 3 months; (3) were high frequency visitors of the ED, defined as visiting the ED 12 or more times in the previous 12 months; (4) ≥50% of ED visits were for chronic pain; and (5) spoke English or French. Inability to provide consent or active psychosis were exclusion criteria for this study.The study protocol was reviewed by the Chair of the institutional REB and approved as a quality improvement initiative. All participants underwent an individual consent process and provided written consent to participate. Informed consent was revisited during 3-, 6-, 9-, and 12-month visits.Consenting patients received rapid (<2 weeks) access to a comprehensive assessment by the Rapid Interprofessional Pain Assessment Program (RIPAP) team. Composition of the RIPAP team depended on patients' needs identified through a chart review completed by a pain specialist and consultation with the referring ED physician. At a minimum, the RIPAP team comprised a physician with focused expertise in pain management, nurse, social worker, and health psychologist. Patients who screened positive for risk of opioid abuse as a result of a high score on the opioid risk tool administered during the clinical interview and/or signs of opioid aberrancies (requests for early prescription) were also referred to addiction medicine. Results from the comprehensive assessment and subsequent treatment recommendations were discussed with the patient to engage them in decisions about their healthcare and ensure that their values, preferences, and goals were reflected in a comprehensive treatment plan. The treatment plan was sent to PCPs and ED physicians with whom outpatient pain case conferences were convened, and input to the plan was concurrently sought. The finalized treatment plan served as an individualized chronic pain care plan that detailed the approach that would be taken to assist the patients in managing their pain on an outpatient basis, as well as recommendations for the management of pain in the event of further ED visits. The care plan was uploaded to the hospital's electronic medical record system; refer to supplementary file for a sample care plan. Patients met with their care team bi-weekly during the first month of intervention and monthly thereafter; additional visits with different members of the team were scheduled as required . Notes from these visits were also uploaded to the hospital's electronic records for members of the patient's circle of care to access. Care plans were “living documents” that were individually tailored and evolved as the study progressed.Patients enrolled in RIPAP were offered all services and specialized programs available at the Hospital Pain Centre (HPC) . Further, patients were provided with access to phone advice from an experienced nurse on the interdisciplinary team. Pain fellows, Acute Pain Services, and experienced HPC physicians worked together to ensure that patient care was optimized as rapidly as possible during admissions. Patients completed questionnaires at baseline and every 3 months during a 1-year follow-up.As recommended by IMMPACT , pain anSecondary outcomes included number of chronic pain-related visits to the ED and healthcare providers, emotional function, sleep disturbance, health-related quality of life, opioid risk, and global impression of change.(1) Chronic Pain-Related Visits to Healthcare Providers. They were assessed using two methods. First, objectively measured visits to the ED in the previous 12 months was assessed at baseline and 12-month follow-up using the electronic medical records of the hospital. Second, during each visit, patients completed a self-report questionnaire reporting on the number of times they visited the ED, PCP, and specialists for chronic pain over the previous 3-month period.(2) Emotional Function. Symptoms of depression were measured using the Patient Health Questionnaire-9 (PHQ-9 [9 (PHQ-9 ), a self9 , a selfα = 0.93–0.95 in undergraduate, community, and outpatient pain samples) [α = 0.75–0.95 in undergraduate and outpatient pain samples) [Anxiety related to pain was measured using the Pain Catastrophizing Scale (PCS ), a 13-isamples) , 46 and samples) .(3) Sleep Disturbance. It was measured using the Insomnia Severity Index , a , a (3) Sdex (ISI –52.(4) Opioid Risk. It was assessed using the Screener and Opioid Assessment for Patients with Pain–Revised (SOAPP-R [(SOAPP-R ), a 24-i(SOAPP-R . The SOA(SOAPP-R . The SOA(SOAPP-R .(5) Health-Related Quality of Life. It was measured using the EuroQol , a EQ-5D-5L . Index s(6) Global Change. Across the course of the study, global change was assessed using the Patients' Global Impression of Change scale (PGIC [le (PGIC ). This mle .One purpose of this pilot study was to establish a proof of concept and obtain information about feasibility of recruitment and retention in preparation for a definitive study. We established our sample size based on resource availability and estimated a capacity to enroll 20 patients.Twenty-one patients with chronic pain were referred between January of 2014 and June of 2015; refer to M = 12.43, SD = 7.25, mild symptoms of generalized anxiety, M = 9.28, SD = 6.41, and moderately severe symptoms of insomnia at baseline. Patients also scored at risk for future aberrant opioid use, M = 23.36, SD = 10.84. All patients had a primary care provider.Patients presented with a diverse range of chronic pain conditions, including neuropathic pain, temporomandibular joint pain, abdominal pain, complex regional pain syndrome, and pain related to inflammatory bowel disease. There was no particular pattern of comorbid medical conditions; we had patients with rare conditions  as well as more common medical problems such as diabetes, hypertension, hyperlipidemia, and asthma. Patients had high healthcare utilization within the 12 months preceding baseline, with a mean 28.6, SD = 18.3, visits to the ED, and 1.2, SD = 1.5, inpatient hospital admissions lasting a mean 7.7, SD = 11.7, days. On average, patients reported moderately severe symptoms of depression, n=1), an unstable relationship with the team (n=1), and rupture in the relationship with the team (or a team member) relative to prescription opioids (n=3).Fourteen patients completed baseline assessment. Five of these patients did not complete the 12-month assessment: three (21%) patients discontinued participation following baseline assessment, one following 3-month assessment, and one following 6-month assessment. Nine patients completed baseline and 12-month assessments. Reasons for attrition included pregnancy , with all but one patient experiencing a reduction in ED visits of more than 50%. Similarly, mean reductions of more than 1-point were observed for pain interference, MDiff = −1.41 , and average 24-hour pain, MDiff = −1.97 , from baseline to 12 months. Five (56%) of the nine patients who completed the study reported a mean reduction in pain interference greater than 1 point, and six (67%) reported a mean reduction in average 24-hour pain that exceeded 1 point. The mean reduction in symptoms of depression was 5.12  points with all but one patient reporting fewer symptoms of depression at 12-month follow-up relative to baseline. Eight of the nine patients who completed the study reported a reduction in risk of future aberrant opioid use with a mean reduction of 7.53  points at 12 months  were identified and provided with rapid access to a comprehensive interdisciplinary assessment and the development and implementation of an individualized chronic pain care plan. Patients were assessed at 3-month intervals over a 12-month follow-up period. The intervention resulted in clinically significant improvements in ED visits, medical visits, pain, physical and emotional function, sleep, and risk for future aberrant opioid use.Rapid interdisciplinary chronic pain assessment and development of a patient-specific care plan reduced self-reported and objective indices of chronic pain-related healthcare utilization by more than 20 visits (>80%) per year from pre- to postintervention. A recent review of prospective cohort trials evaluating the effect of interventions on ED visits among high frequency visitors with varied health conditions reported a mean reduction of 1.91 visits per year across 10 studies, though significant variability was noted between studies (range from +2.79 to −37) . PreviouIntervention effects were evaluated across the core clinical outcomes important for chronic pain trials as recommended by the IMMPACT task force . PatientResults from the present study suggest that rapid interdisciplinary chronic pain assessment and development of an individualized care plan can reduce the risk of opioid misuse. Analysis of patient reported SOAPP-R data indicated clinically relevant improvements in risk of future aberrant opioid use. On average, patients were at high risk (scores ≥ 22) of opioid misuse at baseline and moderate risk (scores 10–21) at 12-month follow-up . ImportaSeveral patients experienced a ruptured relationship with the team regarding opioid prescribing. Three patients were not ready to reduce their opioid use despite efforts made by the team to engage patients in open and nonjudgmental conversations about the risk and benefits of opioid use for chronic noncancer pain and offer opioid substitution as well as agents to mitigate symptoms of withdrawal in case an opioid wean was indicated. This was highlighted by two patients who described feeling as though they were treated as “drug seekers” in the independent program evaluation. Better attention to the team's approach may be needed to effectively work with patients on opioids for whom a different pain management strategy is required due to the high risk of harm, limited benefits observed, or signs of opioid aberrancies.This study has important implications for public health. Chronic pain is rated by family physicians as the second most difficult condition to treat after mental health , 76, andThe results of this prospective cohort study must be interpreted with caution due to several limitations. First, a single-sample prospective cohort design was employed. Without an adequate control group, it was not possible to control for confounds, such as selection bias, expectation, increased attention, or maturation. Further, attrition appears to be a hallmark of frequent ED use , with frAn intervention consisting of rapid interdisciplinary assessment and development of an individualized care plan targeting high frequency users of the ED with chronic pain may be effective at reducing ED use and improving clinical outcomes. Rapid assessments and individualized care plans uploaded to an electronic medical record system may be worth implementing in hospital EDs for high frequency visitors with chronic pain. Additional methodologically rigorous randomized controlled trials are needed to confirm the beneficial effects observed in this study.


Diagnosis of neuropathic pain (NP) can be challenging. The ID Pain (ID-P) questionnaire, a screening tool for NP, has been used widely both in the original version and translated forms. The aim of this study was to develop an Arabic version of ID-P and assess its validity and reliability in detecting neuropathic pain. The original ID-P was translated in Arabic language and administered to the study population. Reliability of the Arabic version was evaluated by percentage observed agreement, and Cohen’s kappa; and validity by sensitivity, specificity, correctly classified, and receiver operating characteristic (ROC) curve. Physician diagnosis was considered as the gold standard for comparing the diagnostic accuracy. The study included 375 adult patients . Overall observed percentage agreement and Cohen’s kappa were >90% and >0.80, respectively. Median (range) score of ID-P scale was 3 (2–4) and 1 (0–2) in the NP group and NocP group, respectively (p<0.001). Area under the ROC curve was 0.808 . For the cut-off value of ≥2, sensitivity was 84.3%, specificity was 66.7%, and correct classification was 73.9%. Thus, the Arabic version of ID-P showed moderate reliability and validity as a pain assessment tool. This article presents the psychometric properties of the Arabic version of ID Pain questionnaire. This Arabic version may serve as a simple yet important screening tool, and help in appropriate management of neuropathic pain, specifically in primary care centers in the Kingdom of Saudi Arabia. Accurate assessment of the type of pain is the first and the most important step for optimal management of chronic pain and improving therapeutic outcome. Chronic pain can be classified into three main categories: nociceptive pain (NocP), neuropathic pain (NP), and the coexistence of NocP and NP, xed pain , 2.The International Association for the Study of Pain (IASP) defines NP as “pain caused by a lesion or disease of the somatosensory nervous system” , 4. A laUnlike NP, NocP is caused by damage to body tissues leading to activation of nociceptors. Pathologically, it is distinguished from NP by a normal somatosensory nervous system and clinically by a sharp, aching, or throbbing pain .et al. (2004) in 10 centers in the Middle East Region reported the prevalence of NP as 41% and NocP as 59% in the patients with chronic low back pain [A pilot study conducted by Hassan ack pain .NP does not respond to the conventional pain treatment. However, it can be managed with specific therapeutic agents such as tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, antiepileptics, opioids, and topical lidocaine.  ThereforThe ID Pain questionnaire (ID-P) is a six-item screening questionnaire . It inclThe study was conducted on Saudi adult patients attending pain management and diabetes clinics at King Fahad Medical City (KFMC), a tertiary hospital in Riyadh, the central region of Saudi Arabia, over a period of one year from March 2016 to March 2017. Patients suffering from moderate to severe NP or NocP pain  for at least three months were included in the study. Patients with pain of unknown origin, mixed-type pain, and diffuse pain which includes fibromyalgia syndrome, myofascial pain, complex regional pain syndrome, cancer pain, and headaches were excluded. Also, patients with substance abuse, chronic alcoholism, severe depression, as well as those incapable of understanding the questionnaire were excluded.The study was approved by the Institutional Review Board at KFMC, Riyadh, Saudi Arabia. Written informed consent was obtained from the participants who met inclusion criteria and agreed to participate in the study.The adaptation procedure was monitored by a seven-member expert panel including two specialists in pain management, an expert in methodology, an expert in clinical research, and an expert in linguistics. The International Guidelines for Cross-Cultural Adaptation of Health Questionnaires and Diagnostic Tests were followed ,22. An iThe first step was the forward translation of the questionnaire to the Arabic language by bilingual translators, whose mother tongue was the Arabic. The first translator was informed about the questionnaire and its applications. The second translator was neither aware nor informed of the concepts being quantified and had no medical or clinical background. Each translator independently produced a translated version of the questionnaire, and then the two versions were synthesized into a single translation.The second step was the backward translation into the original language, which was conducted by two individuals with the source language (English) as their mother tongue. The two translators were neither aware nor informed of the concepts explored, were from non-medical background, and were totally blind to the original version.A meeting, which included the experts and the two translator teams (forward and back translators), was then conducted to assess the semantic and conceptual equivalence between the original and the translated versions. The expert committee’s role was to consolidate all the versions of the questionnaire and develop what was considered to be the pre-final version of the questionnaire for field-testing. All the translations were, thus, reviewed by the committee and a consensus was reached.The final stage of adaptation process was the pretest, which involved administration of the pre-final version of questionnaire to a sample of 30 patients  to detect potential conceptual problems. After completing the form, each subject was interviewed to probe his/her understanding regarding each questionnaire item and the chosen response.Patients were divided into two groups. First group included patients diagnosed with NP by a pain specialist in pain clinics as per the guidelines established by the IASP,  whereas . During the first examination, the participants were interviewed to gather information about socio-demographic and clinical characteristics, and were asked to fill-in the ID-Pain questionnaire. All the subjects were re-evaluated two to four hours later for second examination. The ID-P was again filled by the subjects to assess the time stability of measurements. The assessment of the psychometric properties of the ID-Pain focused on reliability and validity.The Arabic version of the ID-Pain was administered twice to the study population, by the same investigator Sample size was calculated assuming α = 0.05 and p = 41% with power = 0.95 and maximum difference = 0.5. The sample size that is needed to validate the questionnaire for the two groups was 376 patients.Socio-demographic and clinical characteristics of patients were summarized for the whole sample (NP group and NocP group) using frequency (%) for categorical variables and mean  for continuous variables. For continuous variables, normality was assessed using Shapiro Wilk test and histograms. The socio-demographic and clinical characteristics were compared between the two groups using chi-square test for categorical variables and t-test or Mann Whitney’s U test for continuous variables.The ID-P responses were collected in two sessions, one pre-assessment and the other post-assessment. Therefore, for test-retest reliability of the ID-P scale, the percentage observed agreement and Cohen’s kappa statistics were computed and reported. Intra-class-correlation coefficient  between pre- and post-ID-P scale total scores was also computed. To check the internal consistency of the six items of the ID-P scale, Cronbach’s α was computed for the pre- and post-measures of the scale.Initially, median (interquartile range) of the total scores for ID-P were computed and Mann Whitney’s U test was used to compare the scores between NP and NocP groups. Thereafter, to assess the discriminant validity of ID-P in identifying the NP, we used receiver operating characteristics curve (ROC) analyses. A binary variable with physician diagnosis of (NP = 1) versus (NocP = 0) was created. With this binary variable, separate ROC analyses were conducted for the total scale scores of ID-P. These ROC analyses provided the best cut-off points of the scales total scores of ID-P with respect to the corresponding diagnostic values. For each cut-off-point of the scores, sensitivity, specificity, correctly classified, positive likelihood ratio, negative likelihood ratio, were also calculated. Based on Youden’s index , a best p<0.05 was used to reject the null hypothesis. The analyses were conducted using statistical software of SPSS software version 17.0  and Stata version 12 .A statistical significance level of Table 1.The study included 375 adult patients, of which 153  patients were diagnosed with NP and 222  with NocP by expert pain physicians. Demographic and clinical characteristics of the patients are depicted in Table 2).The majority of NP patients had low back pain/referred pain , diabetic polyneuropathy , and lumbo-sciatic pain , whereas, the majority of NocP patients had osteoarthritis , inflammatory chronic arthritis  and mechanical low back pain  , meloxicam , and diclofenac sodium . In the NocP group, 56 (25.2%) patients used paracetamol, whereas diclofenac sodium and meloxicam were used by 40 (18.0%) and 34 (15.3%) patients, respectively.Table 3). The intra-class correlation coefficient (ICC) between pre- and post-ID-P scale total scores for the overall sample was 0.979 , whereas, for NP and NocP groups, the ICC were 0.960 , and 0.976 , respectively. Cronbach’s α for the pre-assessment were 0.506, 0.354, and 0.446 for the overall sample, NP, and NocP respectively. Similar values of the Cronbach’s α were observed for the post-assessment measures of the ID-P scale.The observed percentage agreement and Cohen’s kappa statistics computed for examining the test-retest reliability of the pre-post assessment of the items of the ID-P scale ranged from ‘limited to joints: 93.6%, CK = 0.872’ to ‘feel like hot/burning: 97.9%, CK = 0.956’ in the overall sample; while, it ranged from ‘feel like pins and needles: 95.4%, CK = 0.886’ to ‘feel like hot/burning: 97.4, CK = 0.944’ in the NP group (p<0.001). Using the physician  diagnosis (NP versus NocP) as the gold standard, when the discriminant validity of the ID-P scale was examined using the receiving operating characteristics (ROC) curve analyses, the area under the ROC curve was estimated to be 0.808  for ID-P total score .The medians (interquartile range) for the total score of ID-P scale were 3  and 1  in the NP group and NocP group, respectively  for each of the possible cut-off values of the ID-P total scores are presented in Table 4. For the cut-off value of ≥2, the sensitivity was 84.3%, the specificity was 66.7% and the correct classification was found to be 73.9%. The positive likelihood ratio and negative likelihood ratio were found to be 2.529 and 0.235, respectively. The adjusted odds ratio of the clinical diagnosis of the NP for the per unit increase in the total score of ID-P was 2.58 , p<0.001 (Table 5).Further discriminant statistics (The main advantages of the six-item ID-P questionnaire include its extreme brevity (takes only few minutes to complete) and simplicity . Moreover, it has been found to be of high sensitivity and specificity . Thus, IIn the present study, Arabic version of ID-P was developed to assess its validity and reliability in improving patient care. In order to ascertain that the translated version accurately reflected the original one, a robust approach was followed including a panel of experts and bilingual translators. All the versions were then considered by the expert panel to formulate the final version. Additionally, a pretest was carried out to ensure that the adapted version retained its equivalence in an applied situation. The results of the present study demonstrated that the Arabic version of ID-P is a reliable and efficient method to detect NP. Percentage agreement and Cohen’s kappa statistics showed that there was a high test-retest reliability of the scale in the overall sample as well as in the two sub-groups. The intra-class correlation coefficient between pre- and post-ID-P scale total scores also showed a high level of test-retest reliability. Further, an area under the ROC curve of 0.808  indicated a good diagnostic value. Most importantly, the results showed a good sensitivity and moderate specificity of the Arabic version of ID-P in evaluating patients with chronic pain.p<0.0005) with a cut -off value of ≥3 points, area under the ROC curve of 0.89; p<0.0005, sensitivity value of 0.81, specificity of 0.84, and kappa coefficient of agreement with reference clinical diagnosis of 0.65 [Previous translated and adapted versions of ID-P have also been validated as useful screening tools –20. A cr of 0.65 . Another of 0.65 . In our  of 0.65  of Click here for additional data file.


The benefits of extreme lateral interbody fusion (XLIF) as a minimally invasive lumbar spinal fusion treatment for lumbar degenerative spondylolisthesis have been unclear. We sought to evaluate the invasiveness and tolerability of XLIF with percutaneous pedicle screws (PPS) compared with traditional open posterior lumbar interbody fusion (PLIF).Fifty-six consecutive patients underwent open PLIF and 46 consecutive patients underwent single-staged treatment with XLIF with posterior PPS fixation for degenerative lumbar spondylolisthesis, and were followed up for a minimum of 1 year. We analyzed postoperative serum makers for muscle damage and inflammation, postoperative surgical pain, and performance status. A Roland–Morris Disability Questionnaire (RDQ) and Oswestry Disability Index (ODI) were obtained at the time of hospital admission and 1 year after surgery.Intraoperative blood loss (51 ± 41 ml in the XLIF/PPS group and 206 ± 191 ml in the PLIF group), postoperative WBC counts and serum CRP levels in the XLIF/PPS group were significantly lower than in the PLIF group. Postoperative serum CK levels were significantly lower in the XLIF/PPS group on postoperative days 4 and 7. Postoperative recovery of performance was significantly greater in the XLIF/PPS group than in the PLIF group from postoperative days 2 to 7. ODI and visual analog scale (VAS) score (lumbar) 1 year after surgery were significantly lower in the XLIF/PPS group compared with the PLIF group.The XLIF/PPS procedure is advantageous to minimize blood loss and muscle damage, with consequent earlier recovery of daily activities and reduced incidence of low back pain after surgery than with the open PLIF procedure. Spinal fusion is a surgical procedure used to fuse two or more vertebrae and to stabilize unstable spine segments. Lumbar spinal fusion surgery has been widely used to manage the pain and neurological symptoms in patients with low back pain (LBP) . TraditiAlternatively, more modern, less invasive approaches for lumbar interbody fusion have gained in popularity, one such approach being the mini-open lateral transpsoas approach  . BenefitBy contrast, a comparatively high complication rate of XLIF including postoperative thigh symptoms (range 1–60.1%) has been reported . A recenPatients were candidates for surgery if fusion was indicated because of degenerative lumbar spondylolisthesis and if a full course of conservative care, in particular, drug and brace treatments, had been exhausted. The following criteria were applied: (1) no history of previous lumbar surgery, 2) severe low back and leg pain, and no improvement with conservative therapy for at least 6 months, (3) fusion length ≤3 intervertebral segments, (4) spondylolytic spondylolisthesis or spinal deformities, or both, were excluded . The demographic details of the patients are shown in Table  severe lWe included 102 consecutive patients with degenerative spondylolisthesis grade I and II treated at a single institution by two board certified spinal surgeons who have gained expertise in the XLIF procedure before beginning of the study. From April 2012 to March 2014, 56 consecutive patients underwent open PLIF, and from April 2014 to March 2016, 46 consecutive patients underwent single-staged treatment with XLIF, with posterior PPS fixation and intraoperative CT (O-arm) image-guidance navigation as previously described  without Preoperative and postoperative baseline patient health status were evaluated (for pain-related factors) using the Roland–Morris Disability Questionnaire (RDQ), Oswestry Disability Index (ODI) measured on a 50-point scale, Japanese Orthopaedic Association (JOA) score , and theOn postoperative days 1, 4, and 7, serum creatine kinase (CK) and C-reactive protein (CRP), and white blood cell (WBC) counts were measured. The postoperative pain regimen for all patients included a daily dose of celecoxib (200 mg) for the duration of admission. Use of any analgesic regimens except celecoxib was an exclusion criterion for this study. On postoperative day 1, all patients were asked to state their level of pain using a 10 cm VAS with 10 cm indicating the worst pain imaginable. Additionally, on postoperative days 2 through 7, all patients were asked to state their level of pain using a numerical rating scale (NRS) ranging from 0 to 10, with 0 indicating no pain and 10 indicating the pain of surgery on the first postoperative day. On postoperative days 1 through 7, a physiotherapist recorded the performance status (PS) for all patients established by the Eastern Cooperative Oncology Group (ECOG). All personnel involved with the study patients during admission, including the nursing staff and physiotherapists, were blinded to the approach used and objectives of the study. All adverse events during and after surgery were reported. The total perioperative blood loss was estimated as the total of the intraoperative record and drainage output.Preoperative slip (%) of fused levels was evaluated using lateral X-ray images obtained with the patients in a free-standing posture. Bony fusion was assessed by 2 independent physicians using 3-dimensional computed tomography (CT) at 1 year postoperatively, with the grading of fusion classified according to the system described by Bridwell et al.  . For all tests, P < 0.05 was considered significant.Data were analyzed using the unpaired There were no drop out cases and no revision surgery was needed because of implant failures or adjacent segment disease in either group at 1 year follow-up.P < 0.0001)  and day 7   Fig. .Fig. 2PoThe postoperative surgical pain (VAS score) on day 1 was 6.7 ± 2.2 and 6.9 ± 2.3 for the XLIF/PPS and PLIF groups respectively, with no difference between the groups Fig. . AdditioPostoperative PS scores were significantly greater in the XLIF/PPS group than in the PLIF group from postoperative day 2 to day 7 Fig. .The surgery-related complications encountered in our study (8.6%) were minor and acceptable . There were 5 patients who showed a temporary thigh sensory change and 4 patients who showed a temporary hip flexion weakness in the XLIF/PPS group. There was 1 patient who showed superficial disturbance of wound healing and 1 patient in the PLIF group required repair for durotomy. None of the patients in either group required reoperation for surgical site infection, inadequate decompression or instability at the operative levels.Table Degenerative lumbar spondylolisthesis is one of the disorders most responsive to lumbar fusion. Because of the ability of the interbody fusion technique to correct the listhesis through realignment and stabilization, high rates of improvement on multiple clinical outcome measures after surgery for degenerative lumbar spondylolisthesis have been reported . Recent Open PLIF with instrumentation requires extensive soft tissue and back muscle dissection, which is considered to be problematic in the procedure for conventional lumbar fusion , 20. IndUnexpectedly, we did not find any difference in postsurgical pain from postoperative days 1 to 7 between the groups in the present study. By contrast, the postoperative recovery of activities of daily living (PS) in patients in the XLIF/PPS group was significantly greater than that in patients in the PLIF group from postoperative days 3 to 7. These findings may result from the difficulty and limitations of accurate self-reported acute pain evaluation using simple pain rating scales , 24. DesThis study has limitation that requires further investigation. There was a difference between the two groups in using allograft or autologous bone. This difference could strongly influence postoperative pain, serum creatine kinase and inflammation markers.However, to our knowledge, this is the first study to indicate the comparative invasiveness and tolerability of XLIF compared with traditional open PLIF as a minimally invasive lumbar spinal fusion method to treat degenerative lumbar spinal disease; not only by surgical blood loss and complication rates, but also by evaluating muscle damage, surgical pain, postoperative recovery of daily activities (performance status score), and incidence of low back pain 1 year after surgery. The XLIF/PPS procedure is advantageous to minimize blood loss and muscle damage with consequent earlier recovery of daily activities (performance status) and a lower incidence of low back pain after surgery, but does not result in less surgical site pain than the open PLIF procedure.The XLIF/PPS procedure is advantageous to minimize blood loss and muscle damage, with consequent earlier recovery of daily activities and reduced incidence of low back pain after surgery than with open PLIF.


We explored differences in postoperative pain relief achieved through decompression of the trigeminal nerve compressed by arteries and veins. Clinical characteristics, intraoperative findings, and postoperative curative effects were analyzed in 72 patients with trigeminal neuralgia who were treated by microvascular decompression. The patients were divided into arterial and venous compression groups based on intraoperative findings. Surgical curative effects included immediate relief, delayed relief, obvious reduction, and invalid result. Among the 40 patients in the arterial compression group, 32 had immediate pain relief of pain (80.0%), 5 cases had delayed relief (12.5%), and 3 cases had an obvious reduction (7.5%). In the venous compression group, 12 patients had immediate relief of pain (37.5%), 13 cases had delayed relief (40.6%), and 7 cases had an obvious reduction (21.9%). During 2-year follow-up period, 6 patients in the arterial compression group experienced recurrence of trigeminal neuralgia, but there were no recurrences in the venous compression group. Simple artery compression was followed by early relief of trigeminal neuralgia more often than simple venous compression. However, the trigeminal neuralgia recurrence rate was higher in the artery compression group than in the venous compression group. Trigeminal neuralgia is characterized by pain along the anatomical areas innervated by the trigeminal nerve . The cauOf the 40 patients with arterial compression, the trigeminal nerve was compressed by the superior cerebellar artery in 21 cases, the anterior inferior cerebellar artery in 13 cases, the posterior inferior cerebellar artery in 3 cases, the vertebral artery in 1 case, and by unknown-derived vessels in 2 cases. Venous compression of the trigeminal nerve was relatively complex. Of the 32 patients with venous compression, the trigeminal nerve was compressed by the pons-transverse vein in 13 cases, the pons-trigeminal vein in 7 cases, the cerebellopontine fissure in 5 cases, the middle cerebellar peduncle vein in 3 cases, the petrosal vein in 3 cases, and by an unnamed vein in 1 case.In the arterial compression group, 32 cases had immediate relief of postoperative pain (80.0%), 5 cases had delayed relief (12.5%), and 3 cases had an obvious reduction (7.5%). In the venous compression group, 12 cases had immediate relief of postoperative pain (37.5%), 13 cases had delayed relief (40.6%), and 7 cases had an obvious reduction (21.9%). Immediate pain relief was greater in the arterial compression group than the venous compression group . After operation in the arterial compression group, 6 cases (15.0%) were accompanied with facial numbness and superficial hypoesthesia, 1 case (2.5%) had hearing loss, and 1 case (2.5%) had temporary facial paralysis. After operation in the venous compression group, 5 cases (15.6%) were accompanied with facial numbness and superficial hypoesthesia, 3 cases (9.38%) had hearing loss, and 3 cases (9.38%) had temporary facial paralysis. Statistical analysis showed no difference in facial numbness , hearing loss , or temporary facial paralysis  between the two groups.In the arterial compression group of 40 patients, 37 cases agreed to follow up for 2 years, and 3 cases were missed during the first year of follow up. Trigeminal neuralgia recurred in 6 cases, which is a recurrence rate of 17.6%. Among the 6 cases, 2 cases in this study had severe pain and underwent the operation again, and the other 4 cases had mild pain so they chose an oral carbamazepine treatment. In the venous compression group of 32 patients, 29 cases agreed to follow up, 3 cases were missed during the first year of follow up, and there were no cases of trigeminal neuralgia recurrence. Fisher analysis showed a difference between the two groups (P=0.036), which implied that the long-term recurrence rate in the venous compression group is lower than that in the arterial vascular compression group.Vascular compression is the main pathophysiology mechanism of trigeminal neuralgia. When the compression of blood vessels on the nerve root accumulates, demyelinating change of the nerve root directly affects the afferent impulse of trigeminal nerve fibers , 7. ThisMicrovascular decompression is the first choice of treatment for trigeminal neuralgia , 11. TheAmong the 40 cases in this study with simple artery compression, pain was immediately relieved in 32 cases, which is an early remission rate of 80.0%. Of the 32 cases with simple venous compression, pain was immediately relieved in only 12 cases, an early remission rate of 37.5%. It can be concluded that patients with trigeminal neuralgia caused by simple artery compression saw more immediate pain relief after microvascular decompression than those patients whose neuralgia was caused by simple venous compression.The most common postoperative complications included facial hypoesthesia and hearing loss, while temporary facial paralysis, cerebrospinal fluid leakage, brain stem or cerebellum infarction or hemorrhage and ataxia were also reported. Most cranial nerve injuries are mild, and can gradually resolve. This study found there are more patients with facial numbness, superficial hypoesthesia, hearing loss, and temporary facial paralysis in the artery compression group than in the venous compression group. The cause may be that venous compression is often closely related with the trigeminal nerve, so its separation process has more operations than simple artery compression, thus causing wider range of surgical imaging of trigeminal nerve. Literature reported postoperative recurrence of MVD was 3% ~ 20%, and the recurrence often occurred 2 years after the operation . This stWhile patients with trigeminal neuralgia caused by simple artery compression reported more immediate pain relief after microvascular decompression compared to patients whose neuralgia was caused by simple venous compression, the long-term recurrence rate of the latter was lower than that of the former. There were no differences in postoperative complications between the two groups.This study included 40 male and 32 female cases, and the average age was 63.7 ± 6.60 years old. There were 56 cases above 60 y, and the disease course was 3 - 16 y. Patients of the arterial compression group all showed lateral facial paroxysmal pain, including first branch pain in 6 cases, second branch pain in 9 cases, third branch pain in 7 cases, 1+2 branches pain in 5 cases, 2+3 branches pain in 10 cases, and all three branches pain in 3 cases. Patients of venous compression group all showed lateral facial paroxysmal pain, including first branch pain in 3 cases, second branch pain in 10 cases, third branch pain in 6 cases, 1+2 branches pain in 3 cases, 2+3 branches pain in 8 cases, and all three branches pain in 2 cases.All patients were given surgical treatment after failed preoperative treatments including oral administration of carbamazepine or acupuncture, etc. All compressions of the trigeminal nerve were due to simple arterial or venous compression. The study was approved by the Ethics Committee of each hospital. Written informed consent was obtained from all the patients prior to surgery, and all the patients consented to the submission of this report for publication.Microvascular decompressions were all carried out via a routine suboccipital retrosigmoid approach. Cerebrospinal fluid was drained slowly under a microscope, and when the cerebellum collapsed, the area was explored. Adhesion between arachnoid and cranial nerves was sharply separated and fully released. The arteries responsible for the compression were found, and Teflon cotton was placed to block the blood vessel in the brain cistern of the trigeminal nerve.For the larger responsible veins, especially the trunk of super petrosal vein complex, they were retained. Small veins and branches of super petrosal veins were blocked with electric coagulation, adhesion, and compression to withdraw venous compression, and then the same operation was carried out between the responsible veins and the trigeminal nerve. None of the patients were given drainage tubes, and the meninges were sutured tightly. Dura mater defect was repaired with autologous fascia, and the scalp was sutured. Intraoperative photographs of trigeminal nerve lysis is shown in Figure Recovery from trigeminal neuralgia was regularly inspected and recorded after operation, and the improvement was divided into four types: (a) Postoperative pain was relieved immediately, and entirely disappeared within 1 day after the operation; (b) pain relief was delayed, and postoperative pain gradually decreased to zero within 1 month; (c) the pain decreased, but still a small dose of carbamazepine was needed to control pain after operation; (d) the pain was not obviously improved. Recurrence referred to the repetition of pain after a period of complete relief.P < 0.05 was considered statistically significant.SPSS 16.0 software was used for the statistical analysis. For the data analysis, the mean ± standard deviation was employed. We used the χ2 or Fisher analysis to test associations between categorical variables, and the t-test for continuous variables.


Fibromyalgia is a common chronic pain condition that exerts a considerable impact on patients' daily activities and quality of life.Objectives: The main objective of the present study was to evaluate kinematic parameters of gait, functional performance, and balance in women with fibromyalgia syndrome.Methods: The study included 26 female patients with fibromyalgia (49.2 ± 8.0 years) according to the criteria of the American College of Rheumatology, as well as 16 pain-free women (43.5 ± 8.5 years). Gait and balance parameters were extracted from video recordings of participants performing several motor tasks. Non-linear dynamic of body sway time series was also analyzed by computing the Hurst exponent. In addition, functional performance and clinical pain were obtained by using standardized motor tests  and self-report questionnaires .Results: Walking speed was significantly diminished (p < 0.001) in FM patients as compared to pain-free controls, probably due to significant reductions in stride length (p < 0.001) and cycle frequency (p < 0.001). Analyses of balance also revealed significant differences between fibromyalgia and pain-free controls on body sway in the medial-lateral and anterior-posterior axes . Several parameters of gait and balance were significantly associated with high levels of pain, depression, stiffness, anxiety, and fatigue in fibromyalgia.Conclusion: Our data revealed that both gait and balance were severely impaired in FM, and that subjective complaints associated with FM could contribute to functional disability in these patients. These findings suggest that optimal rehabilitation and fall prevention in fibromyalgia require a comprehensive assessment of both psychological responses to pain and physical impairments during postural control and gait. Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain sensitivity and fatigue, as well as by cognitive and affective symptoms . Furthermore, considering that activity and balance fluctuations have well defined fractal properties in a wide range of time scales, we also aimed to apply nonlinear analyses to evaluate the dynamic of these balance fluctuations in pain-free controls and FM patients. This nonlinear approach allows an evaluation of the autocorrelation in successive displacements, giving us information about possible disturbances in motor control mechanism to correct balance.n = 18), followed by antidepressants (n = 16), and anxiolytics (n = 9). For medical and ethical reasons, medication was not discontinued during the study. At the time of recruitment, all participants were verbally informed about the details of the study and provided written consent. The study was approved by the Ethics Committee of the Balearic Islands (Spain) (reference IB-1284/09).Twenty-six women diagnosed with fibromyalgia and 16 pain-free women with comparable age and sociodemographic characteristics were recruited from different health centers and patients' associations in Majorca (Spain). The average duration of FM diagnosis was 10.8 ± 7.7 years Patients were included in the study if they fulfilled the 1990 classification criteria of the American College of Rheumatology for fibromyalgia. Participants were excluded from the study if they reported any other musculoskeletal rather than fibromyalgia, or any neurological disorder. Regarding medication intake, most FM patients were taking analgesics, relaxants, or NSAIDs  : The 6MWT is a functional walking test in which subjects are instructed to walk for 6 min as quickly as possible. This test has been used to assess individuals with mobility deficits : This task is a standardized test for assessment of functional mobility. The task is performed by using an ordinary armchair (45 cm in height) and a stopwatch. Subjects are seated with their back against the chair and instructed to stand up, walk three meters, turn around, walk back to the chair, and sit down at an ordinary comfortable speed  , and on the tip of the hallux. Subject's motion was digitally recorded with a video camera at 210 frames per second (Casio Exilim EX-FS10). The camera was positioned at a distance of 3 meters from the carpet to visualize changes in position, velocity, and acceleration of anatomical points along the x-axis. Gait velocity (cm/second), walking duration (seconds), cadence (number of steps/minute), percentage of time in the two phases of the gait cycle (stance and swing phase), and percentage of time with single and double support were computed.- Gait and balance parameters were obtained in FM patients and pain-free controls by using the following functional tasks:Raw scores obtained from self-report questionnaire (FIQ).Performance scores on standardized motor function tasks .Kinematic parameters extracted from video recordings: gait velocity (cm/sec), gait duration (sec), cadence (steps/min), stride, and step lengths (cm), percentage of time in the stance/swing phase, and body sway variability in the anterior-posterior and medial-lateral planes (cm). Open-source software for computer vision analysis of human movement  method  to the scaling function .The null hypothesis that data were sampled from a normally distributed population was examined by using Shapiro-Wilk tests, and differences between patients and pain-free controls were analyzed by using parametric Student of Cohen : 0.2 ≤ d2 ± 4.2 vs. 25.5 kg/m2 ± 4.1) . Mean and standard deviation of FIQ scores in fibromyalgia patients are displayed in Table Fibromyalgia patients and pain-free controls were comparable on age , weight (68.6 kg ± 10.9 vs. 64.2 kg ± 10.9), height (161.1 cm ± 6.4 vs. 163.3 cm ± 7.0), and body-mass index (26.5 kg/mt(29) = −8.3, p < 0.001], and took more time to stand-up and to walk a distance of 3 meters (TUG) as compared with pain-free controls . Moreover, ratings on self-perceived effort  after performance on 6MWT  and TUG tests  were significantly higher in fibromyalgia than in pain-free controls. Finally, FM patients reported increased risk of falls  in comparison with pain-free controls . The effect sizes were medium-to-large for all group comparisons.Table t(31) = −8.3, p < 0.001], cadence (steps/minute) , stride length , and percentage of single support  and swing phase , as well significant increased gait duration  in comparison with pain-free participants. Same effects were also yielded when values were referenced to each subject's legs  (Table t(27) = 4.6, p < 0.001] and medial-lateral directions  than pain-free controls.Analyses of kinematic parameters further indicated that FM patients had significant deficits in gait and balance. Again, the effect sizes were medium-to-large for all group comparisons. FM patients displayed significant reductions in gait velocity  and medial-lateral axes . In both cases, the H exponents were close to 0.5 in fibromyalgia patients and around 0.3 in pain-free controls , increased time to perform the TUG test , reduced distance to walk in 6 min in 6MWT test , gait velocity , cadence  and stride lengths , as well as increased gait duration  and body sways in the medial-lateral axis . High ratings on fatigue and stiffness were also associated with reduced percentage of single support . In addition, high ratings on stiffness were related to enhanced perceived effort after completion of the 6MWT test , and reduced stride  and step lengths during the gait cycle . High ratings on the physical function scale were significantly associated with high risk of falls  and increased perceived effort after completion of the TUG , as well as with reduced distance walked in 6 min during performance of 6MWT test . The number of missed days of work were significantly associated with high risk of falls , enhanced perceived effort after completion of the 6MWT test  and reduced distance to walk in 6 min in 6MWT test . Low ratings on ability to do job were significantly associated with high risk of falls  and increased body sways in the medial-lateral axis . High ratings on the rested scale were significantly associated with reduced distance walked in 6 min during performance of 6MWT test . Finally, ratings on depression were correlated with risk of falls , increased time to perform the TUG test , enhanced perceived effort after completion of TUG , and reduced stride  and step lengths . High ratings on anxiety were significantly associated with high risk of falls  and increased body sways in the medial-lateral axis .In order to further assess if altered motor function was related to clinical symptoms in fibromyalgia, Pearson correlations were computed between motor performance scores and ratings on the different FIQ scales. Results indicated that high ratings on pain intensity were significantly associated with enhanced risk of falls  during performance on several motor and balance tasks in fibromyalgia patients and age-matched pain-free controls. Our results indicated that both gait and balance were severely impaired in FM, and that several parameters of motor performance were linked to clinical symptoms associated with FM.Gait parameters such as speed, cadence, stride and step lengths, percentage of stance, and swing phases, and support base were significantly impaired in FM patients. These findings are in accordance with previous studies showing that FM patients displayed slower cadence during gait compared to pain-free controls  than in FM patients . These findings were in agreement with previous data observed in healthy individuals  might contribute to reduce physical activity and to alter gait and balance parameters  in chronic back pain (Vlaeyen and Linton, The present study has some limitations that should be taken into account for the interpretation of the results. Two-thirds of our FM patients were currently taking analgesic and antidepressant medication during data collection and, therefore, the possible side effects of these drugs on balance and gait cannot be completely discarded. In this sense, a recent study has shown that antidepressant use was one of the possible mediators for the association between obesity and risk of falls in community living older persons (Mitchell et al., In conclusion, our results point toward significant impairments in balance in FM patients as compared with pain-free controls, as assessed by self-reports, standardized motor function tests and kinematic parameters extracted from participants' video recordings. We found that pain intensity, stiffness, fatigue, depression and anxiety were the most relevant factors in explaining some gait and balance deficits in FM. We have also found that FM patients displayed an abnormal pattern of body sways during a balance task, which could be associated with changes in the motor control system and explain a higher risk of falls. All these findings highlight the relevant role of postural control and balance for daily activity functioning in FM. Thus, specific activities directed toward the modification of these altered gait and balance patterns may be included in regular physical intervention programs for FM. This represents a relevant contribution considering that most of previous research on functional disability in FM was based on retrospective reports or on self-report measures rather than on objective measures of gait and balance.IdSC designed the study, conducted the experiments and wrote the first version of the manuscript. All the authors contributed substantially to data analysis, interpretation of the results and critical revisions of the manuscript. The final version was approved by all authors. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Classical trigeminal neuralgia (TN) is a severe neuropathic facial pain disorder associated with increased risks of anxiety and depression. Converging evidence suggests that chronic pain pathophysiology involves dysfunctional pain-related and emotion-related networks. However, whether these systems are also among the culprit networks for TN remains unclear. Here, we aimed to assess TN-related anatomical and functional brain anomalies in pain-related and emotion-related networks. We investigated differences in gray matter (GM) volume and the related resting-state functional connectivity (rsFC) between 29 classical TN patients and 34 matched healthy controls. Relationships between brain measurement alterations, clinical pain and emotional states were identified. A longitudinal observation was further conducted to determine whether alterations in the brain could renormalize following pain relief. Reduced GM volumes in the bilateral amygdala, periaqueductal gray (PAG) and right insula were found in TN patients compared with healthy control subjects. Whole-brain rsFC analyses with the four above-mentioned anatomical regions as seeds identified three significantly altered functional circuits, including amygdala-DLPFC, amygdala-mPFC and amygdala-thalamus/putamen circuitry. The amygdala-DLPFC and amygdala-mPFC circuits were associated with clinical pain duration and emotional state ratings, respectively. Further longitudinal analysis found that rsFC strength abnormalities in two fronto-limbic circuits  were resolved after pain relief. Together, structural and functional deficits in pain-related and emotion-related networks were associated with TN patients, as demonstrated by our multimodal results. Pain relief had protective effects on brain functional connectivity within fronto-limbic circuits. Our study provides novel insights into the pathophysiology of TN, which may ultimately facilitate advances in TN intervention. Trigeminal neuralgia (TN), a severe neuropathic pain disorder, is estimated to affect one in 15,000–20,000 people worldwide  scheduled to undergo MVD surgical procedures for the treatment of classical TN and 34 control subjects  with similar distributions of age, gender and years of formal education . All patients had right-sided pain and met the criteria of the International Headache Society for TN. No patients had undergone prior MVD surgery or other treatments  for TN or received tricyclic antidepressants, opioids, or serotonin/norepinephrine reuptake inhibitors. Individuals were excluded if they had a history of other chronic pain conditions, psychiatric disorders, stroke/cerebrovascular ischemia, any other neurological or sensory deficits or TN attributed to another disorder. Written informed consent was obtained from each participant prior to study inclusion, and the study was approved by the local ethics committee of the Chinese People’s Liberation Army (PLA) General Hospital.All subjects were asked to draw the extent of their neuralgia on a visual analog scale . The 17-item Hamilton Depression Rating Scale (HAMD) and the 14-item Hamilton Anxiety Rating Scale (HAMA) were used to quantify the depression- and anxiety-related symptoms of the subjects, respectively. The HAMD was administered to each participant by a psychiatrist using the Structured Interview Guide for Hamilton-Depression interview format  of pain-relieved patients was subjected to pain ratings, emotional evaluations and MRI scans similar to the preoperative protocol approximately 4–6 months after MVD surgery.Additionally, a follow-up subset  sequence with the following parameters: repetition time = 2000 ms, echo time = 30 ms, flip angle = 90°, thickness/gap = 3.5 mm/0.5 mm, slices = 36, field of view = 224 × 224 mm2, voxel size = 3.5 × 3.5 × 3.5 mm3, and a total of 240 volumes. During the scan, participants were fitted with soft earplugs and instructed to keep their eyes closed, to remain motionless, and not to think of anything in particular. After the scanning, a simple questionnaire indicated that no participants had fallen asleep.TN patients stopped their pain medication for at least 24 h prior to MRI scan. MRI data acquisition was performed on a GE750 3.0 T scanner with an eight-channel phase array head coil. High-resolution structural images were collected using a sagittal Fast Spoiled Gradient-Echo (FSPGR) sequence with the following parameters: repetition time (TR), 6.7 ms; echo time (TE), 2.9 ms; flip angle, 7°; slice thickness, 1 mm; no gap; 192 sagittal slices; field of view (FOV), 256 × 256 mmP < 0.05. Because of the small anatomical size of brainstem nuclei, we further conducted a region of interest (ROI) approach to restrict analyses to the brainstem using the Harvard-Oxford subcortical structural mask, a correction for multiple comparisons was performed within this mask separately.Structural data processing and analysis was performed with Statistical Parametric Mapping SPM12. Subsequ1) and Data Processing and Analysis for (Resting-State) Brain Imaging . Group-level rsFC maps were obtained by performing one-sample t-tests on the z-maps for each individual seed. The significance level of one-sample t-tests was determined by the cluster-forming threshold of P voxel < 0.001 with an FWE corrected cluster of P < 0.05 using SnPM under SPM12.Then, we performed functional connectivity analysis using the seed-based approach. Regions with significantly morphological differences between TN patients and HCs (see “Results” section) were used as seeds in the subsequent rsFC analysis. The rsFC map for each seed region of interest was obtained by computing whole-brain voxel-wise correlations associated with the mean time course of the seed. The correlation coefficient maps for each individual seed were further normalized with Fisher’s P < 0.05.Differences in rsFC z-maps between TN patients and HCs for each region of interest were separately examined using a general linear model . Similar to anatomical analysis, multiple comparisons were also corrected using the nonparametric method in SPM12, we also set the significance level of the cluster-forming threshold to 0.01 with a FWE corrected cluster of To explore the relationships between altered brain imaging indices (GM volume and rsFC) and behavioral measures , correlation analyses were performed using mean values of GM volume or rsFC strengths within regions showing significant group differences against behavioral measures, controlling for age, gender and education level.t-tests were performed to compare pre- and post-treatment (4–6 months after MVD) brain imaging indices (GM volume and rsFC) using region of interest (ROI)-based VBM and rsFC analyses. Values of GM volumes and rsFC strengths for each follow-up participant were extracted from ROI masks derived from the above-identified clusters that showed significant structural and functional alterations in TN patients. We further investigated whether the reversibility in functional connectivity correlated with TN duration.To determine whether GM volume and rsFC strength abnormalities associated with TN are resolved after pain relief, paired sample Table P < 0.05, FWE corrected; Figure Compared with HCs, the TN patient group showed smaller GM volumes in the bilateral amygdala, PAG and right insula  resolved such that the rsFC strengths were no longer significantly different from those of the HCs Figure . No signIn this study, we initially identified structural markers of TN in pain-related and emotion-related regions of the human brain, including the PAG, right insula, and bilateral amygdala. Using these four regions as seeds in subsequent rsFC analyses, three amygdala-related functional circuits that differed between TN patients and HCs were identified and associated with clinical pain duration and emotional state ratings. Further longitudinal analysis of patients with pain relief following effective treatment revealed that brain abnormality normalization is restricted to functional fronto-limbic circuits. As the pain- and emotion-related regions are involved in TN, further attention to these regions as potential therapeutic targets and therapeutic strategy guides are warranted.Growing evidence supports the concept that chronic pain is associated with dysregulation in descending pain modulation  the organization of the pain-related pathways predominately target the contralateral hemisphere; and (2) from the functional lateralization of amygdala potentially involving differential rsFC patterns in left- and right-sided hemisphere (Baas et al., For the rsFC analysis, we utilized ROIs derived from VBM results as seed regions. Although the structural changes did not significantly correlated with changes in functional connectivity, findings supported by these two modalities, would take advantage of the cross-information from each modality, thereby potentially enhancing power to detect imaging signature for TN (Geng et al., First, because the subjects were relatively heterogeneous and the sample size in each cohort was small, the detection power was considerably reduced. Indeed, in the analysis of detecting GM and functional differences between TN patients and HCs, no clusters survived at the voxel-wise thresholds of 0.001. Thus, we used the voxel-level correction threshold of 0.01 to balance the control over false positives and the maintenance of sufficient power to detect differences. This exploratory investigation of GM and functional changes needs to be replicated in larger cohorts. Second, functional brain networks constructed from the rsfMRI data were largely constrained by structural white matter pathways (Honey et al., By combining structural and functional imaging data from a cohort of TN patients and matched HCs, we identified GM volume differences in the pain- and emotion-related networks. Functionally, three altered fronto-limbic circuits were identified and associated with clinical pain duration and emotional state ratings. Further longitudinal analysis of brain alterations following pain relief resulted in the reversal of functional mPFC-amygdala and DLPFC-amygdala circuitry. Taken together, these multimodal results support the previously reported pain- and emotion-related networks deficits in TN patients. Perhaps more importantly from a therapeutic perspective, the directionality of TN-related effects observed at the brain level differed from those previously reported on peripheral trigeminal injury alone in TN patients.YZ, ZM, LP, ZL, XL, JZ and XY contributed to the conception of the study and to acquisition, analysis and interpretation of data. All the authors drafted the work and revised it critically for important intellectual content. Final approval of the version to be published was performed by all authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.