Background: The use of diverse therapies combined with a multidisciplinary approach and prevention initiatives for patients with chronic non-malignant pain (CNMP) can improve health and have a positive impact on psychotropic drug use and the self-management of pain. Purpose: This purpose of this study has been two-fold: to conduct a literature review with a view to selecting best evidence recommendations for CNMP and to prioritize self-care recommendations using a participatory methodology for the analysis and selection of interventions. Methods: A qualitative, descriptive, and documentary method based on participatory action research was used. Findings: Based on the study results, a multimodal psychosocial intervention program has been designed for CNMP that includes psychoeducational therapy, pharmacological therapy, physical exercise, and health assets. Discussion: The findings are consistent with previous studies underlining the need to invest in resources for the management of CNMP, including strategies for good differential diagnoses and pharmacological treatments combined with non-pharmacological treatments to confer greater well-being for people living with pain who want to participate in their own recovery. Chronic non-malignant pain (CNMP) is considered a public health problem due to its high prevalence among the population. The condition has a significant impact on the quality of life of patients and their families and is largely managed in the primary care setting . Pain isUnder the maxim “constant pain needs constant control,” the nurse, social worker, and physician Cicely Saunders 1918–2005) introduced the concept of “total pain” as a multidimensional construct that includes the social environment and emotional processes of patients with chronic disease. In a similar line, expanded gate control theory of pain posited that sensory-discriminative, cognitive-evaluative, and motivational-affective factors affect how patients experience chronic pain. Pain catastrophizing and acceptance are two interrelated psychological constructs that also influence the perception of chronic pain. These constructs mediate the relationship between the unpleasant experience of pain and suffering  and are  introducIn the treatment of chronic pain, early detection is key as it can reduce catastrophizing thoughts and depression and improve patients’ ability to perform activities of daily living . Given tAmong the factors associated with pain in women, highlighted the greater frequency of chronic diseases, especially musculoskeletal disorders, poorer functional status, higher levels of psychological stress, and less physical activity ,12.Combined therapy programs based on a multidimensional and multidisciplinary approach should be developed to improve the health of the general population and treat chronic pain.These therapies should be coupled with prevention initiatives, information, physiotherapy, clinical guidelines, as well as psychotherapeutic and pharmacological treatment, rehabilitation, and psychoeducation for both patients and families. Such interventions, whose efficacy and effectiveness can be evaluated, can also have an impact on the use of psychotropic drugs and the self-management of pain ,14.The salutogenic model, which is based on resistance and resilience in response to everyday life situations, focuses on personal health assets to effectively manage conflictive situations . EvidencAs a conceptual framework to select the dimensions to be reviewed, the Patient-Reported Outcomes Measurement Information System (PROMIS) model was followed ,24, baseStudy has a three-fold purpose: (i) to review the literature on CNMP and select the best evidence recommendations for chronic pain; (ii) to prioritize self-care recommendations using a participatory methodology involving the analysis and selection of interventions; and (iii) design a multimodal treatment program for people suffering from chronic pain.These results are part of the development and evaluation of a multimodal intervention protocol through information technology in primary care, as part of a broader research program aiming to improve pain management. In this document we will focus on the second objective “to prioritize self-care recommendations, with participatory methodology”.A three-stage transformative, participatory, and qualitative approach based on participatory action research (PAR) was used, as a working methodology. A multimodal pain therapy (MPT) protocol was developed using the three-stage Emergence, Interaction framework .Ethical aspects of this study were approved by the Cordoba Research Ethics Committee of the Andalusian Public Health System. Informed consent (S0452) was approved by the Cordoba Research Ethics Committee and completed by the participants.In the initial emergence phase, a multidisciplinary team was formed. The team comprised clinical and scientific experts from different fields of knowledge with more than 15 years of experience . All of them actively participate in the follow-up of patients with chronic pain in the primary sector of care. Participants in each category were recruited to represent diverse care settings from various provinces of Andalusia, Spain  and clinical settings .The problem was analyzed using a biopsychosocial approach by people with CNMP.We conducted a systematic review, following SIGN guidelines. The literature was identified according to an explicit search strategy selected according to defined inclusion and exclusion criteria evaluated against consistent methodological standards. As a result, applying judgement allowed us to develop the synthesis of the main grounds of evidence and extract the recommendations in four dimensions: pharmacological therapy, psychoeducational therapy, physical exercise, and health assets, by consensus of the reviewers, which have been considered most applicable to clinical practice. All studies used for this review were ranked according taking into account their levels of evidence in accordance with the Scottish Intercollegiate Guidelines Network system .A literature review of the databases PubMed, Campbell Library and Cochrane Library Plus as well as the internet search in order to find guidelines or other documents related to the objective of the study. The websites of various official organizations and institutions were consulted: World Health Organization (WHO) and Pan American Health Organization (PAHO), National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), CPG Infobase: Clinical Practice Guidelines, Scientific societies, was performed using the following key search terms: Chronic Pain (MeSH terms), Mind-Body Therapies (MeSH terms), Pain Management (MeSH terms), Acceptance and Commitment Therapy (MeSH terms), Multidisciplinary (MeSH terms), Pharmacological (MeSH terms) and Biopsychosocial Model (MeSH terms).The search was limited to publications from Janury 2018 to October 2020. The indicator for locating the documents was that they had been published in the last 5–10 years. Priority was given to secondary research documents followed by primary research.Manuscripts were retrieved and reviewed utilizing the following inclusion criteria: subjects with CNMP, defined as pain lasting for more than three months; adult participants (aged ≥ 18); experimental intervention aimed at reducing chronic pain that involves a physical component and a psychological and/or social component; multimodal intervention, pharmacological and non-pharmacological treatment; studies with more than 20 subjects in each treatment arm to reduce the bias that can occur in small samples; studies with statistical significance; mixed studies , randomized controlled trials, and non-randomized longitudinal studies (prospective and retrospective). Exclusion criteria included the following: patients with acute pain (duration < 3 months); patients with palliative, cancer-related or post-surgical pain; pediatric population; interventions involving surgery; studies with insufficient samples (<20 subjects), studies without abstracts and/or incomplete text, dissertations, editorials, letters, and non-English articles.The recommendations were adapted to the level of understanding and cultural environment of the expert patients who participated in the selection and prioritization of the recommendations for their subsequent implementation and to evaluate their effectiveness.The nominal group comprised patients diagnosed with CNMP, caregivers, experiential experts, as well as the expert professionals who conducted the literature review, drafted the questionnaire, and participated as observers and moderators of the nominal group. They were recruited to participate in a 1-day workshop held in Cabra, Córdoba, Spain, on 14 February 2019.To select and validate the priority recommendations for the target population, two actions were carried out as follows.A 5-point Likert scale questionnaire containing closed and open questions was designed to measure the expert participants’ (patients and caregivers) degree of agreement with the items. The response anchors were: 5 (very high), 4 (high), 3 (moderate), 2 (low), and 1 (very low) see .The content of the questionnaire was validated using a variant of the Delphi method. Specifically, we used the modified Delphi, what is known as the Estimate, Feedback, Talk, Estimate (EFTE), conversational, or face-to-face Delphi . The DelThe main objective of the dynamics was to validate and prioritize the recommendations obtained in the bibliographic review, grouped into the four dimensions identified in that review. We also sought to ensure that the final wording of the recommendations provided by the questionnaires was accessible and easy to understand. All this was materialized through group discussion by asking questions such as: “Can postural hygiene, relaxation and stretching exercises improve the health and quality of life of a person with chronic pain? Can managing emotions such as fear or sadness in the face of pain help me feel better? Can identifying the resources (or lack of them) that we have in our environment  help me to improve my health? To what extent does not abandoning the prescription of medications affect our health?Through the completion of the questionnaires that included the recommendations which were the origin of these and other questions, and the feedback of the debate originated in the different rounds of the technique, the necessary degree of convergence of the individual estimates was reached, achieving consensus and stability in the panel’s responses, which guided the data analysis and decision making. The result was that a score was obtained for each recommendation within every dimension, which made it possible to estimate the consensus through the calculation of percentages, a measure agreed upon by the research group. It must be noted in this regard that there is not a single way of estimating consensus, according to the scientific literature on the subject.Regarding the stability of the panel, the members of the research team who assumed the roles of moderator and observer determined that, once no significant variability in the opinions of the experts was achieved between successive rounds, the process was to be finished.n = 36 participants from whom n = 8 were selected as principal investigators and co-researchers for their experience and management in the nominal group and n = 28 expert patients, including n = 20 women and n = 8 men who are familiar with and manage their CNMP process, who were intentionally selected.The nominal group consists of a total of To obtain heterogeneous responses, we partnered with the Local Health Action Network, Fibromyalgia Association, Socio-educational Groups, Trainers of The Patient School of the southern health area of Córdoba, to recruit patients and family members.Applying a theory called “Belbin’s team roles”, the team meets the ideal profiles for the development of this research work .Thus, we can find that in homogeneous groups, as in our case, the approximate size of a Delphi panel is generally less than 50; in heterogeneous groups, it can be hundreds.The inclusion criteria for patients in this study were: individuals with chronic musculoskeletal pain, patients ≥ 18 years of age with pain of any location, with a duration of ≥3 months, an intensity of ≥4 on the Visual Numerical Scale (VNS), and with one of the following characteristics: continuous pain, intermittent pain ≥ 5 days a week.All participants were asked to sign an informed consent form.The participants in the nominal group were randomly divided into four smaller groups of 7 participants each in different rooms. Each group was led by two professional experts (literature reviewers and those who designed the questionnaire). One of the experts acted as the moderator and the other as the observer. The moderator was responsible for informing the participants about the session and handing out the questionnaires with the recommendations selected for each dimension  so that each participant could analyze and present their ideas. The observer was responsible for taking observational notes on the behavior, interactions, and verbalizations of the group members.First, a small group discussion was held to reach consensus on the proposed priorities for each dimension, followed by a discussion with all participants. The group was asked to rate each idea using a previously defined 5-point quantitative scale in which the highest value was assigned to the approach considered most important. The scores obtained for each of the ideas were then transcribed. Once the scores were tallied, they were written down and a discussion was held on the points for which agreement had not been reached. The proposals were put to a new vote and the participants voted again for the factors they considered most important. The votes were then counted by factor, the responses were ordered from the highest to the lowest numbers of votes, and the results were read out loud to the participants. Given the substantial number of recommendations selected by the participants, the group agreed that there should be no more than 8 recommendations in each of the 4 dimensions of the approach to CNMP. Finally, specific recommendations were made for physical exercise, psychoeducation, health assets, and pharmacological therapy for the treatment of CNMP.A total of 225 citations were identified during the search, which after a first reading were excluded because they did not meet the objective of the study. After a second review, 42 citations were included. Eight documents were located in other databases, of which five were selected. The final review included 14 studies, of which six were systematic reviews, five were narrative reviews and three were clinical guidelines.In order to analyze the results, the statistical procedures were carried out according to the nature of the research conducted. With the total score obtained for each recommendation, as well as its maximum and minimum scores, the median was calculated, given the type of scale used (Likert) and the average to prioritize among the recommendations with the same median of the same dimension.As the questionnaires included open-ended questions, as well as the account provided by the observers, a critical analysis of the discourse was carried out, which provided a battery of suggested recommendations which could be included in the multimodal protocol and that had not previously been reflected in the questionnaire provided.Another result obtained thanks to the interaction between the members of the panel of experts was to adapt the wording of the recommendations or make it as adequate as possible to a clear, concise, accessible and understandable language for the target population.As regards psychoeducational therapy , the priThe experts’ priority recommendations regarding health assets are shown in In what follows, we present the responses of the nominal group to the open-ended question in the section titled “Other recommendations ”. The participants were asked to provide recommendations for aspects not reflected in the questionnaire but that could be included in the multimodal protocol. As regards exercise, the expert patients indicated that walking and receiving massages can improve their health. In relation to the psychoeducational component, they pointed to the need to combine therapies and work with professionals from different specialties. For the health assets component, they recommended engaging in cooperative community activities that provide CNMP patients with the opportunity to share their experiences, while in the pharmacological section, the participants referred to their lack of confidence in generic drugs and the importance of shared decision making and drug safety.This study has prioritized evidence-based interventions for the management of CNMP with a participatory methodology, a public health problem that entails a significant cost burden not only for patients and their families, but also for the health system as a whole as they frequently resort to primary healthcare and emergency services and may even require hospitalization.To gather the opinions and identify the demands of the CNMP patients, a participatory method was used. The aim was to place these patients at the center of their own transformation and empower them, as well as to give them the opportunity to create support networks and strategic connections among the community stakeholders.As the results have shown, the expert patients reached a consensus regarding the prioritization and choice of recommendations as a strategy for implementing the multimodal CNMP treatment program. Through collaboration between professionals and expert patients, as well as the application of diverse treatments that provide health benefits, practical solutions to complex problems have been found. The priority recommendations of the expert patients are in line with the reviewed literature, which has shown that multimodal treatments are preferable to single treatments . Other aIn the primary care setting, the prescription of medications, including opioids , is the Non-pharmacological therapy and non-opioid pharmacological therapy are preferred for chronic pain. If opioid therapy is considered, the expected benefits/risks should be assessed. If opioids are used, they should be combined with non-pharmacological therapy and non-opioid pharmacological therapy, as appropriate . MoreoveSelf-care programs under the guidance of health professionals may also influence health outcomes, such as preventing catastrophizing thoughts that modulate pain, such as the belief that pain cannot be controlled and exaggerating the threat. In this regard, self-care can improve patients’ capacity for self-management as they actively participate in their treatment. As Moore et al.  suggesteThe findings of this work are consistent with previous studies on the need to invest in resources for pain management that include strategies for good differential diagnoses and pharmacological treatments combined with non-pharmacological treatments, as they can be beneficial for patients not only in terms of improving pain, but also in reducing anxiety and depression, facilitating rest, improved well-being, and the desire to participate in their own recovery.For people with chronic pain, multiple non-pharmacological therapies are also available, such as physical activity to improve coordination, reduce pain, and improve mood.According to our results, the R4 statement, “it is important to be able to continue doing activities that are in my daily life  and help me feel better” is consistent with the evidence found on ACT . Thus, in a clinical trial conducted in Spain on the cost-utility of ACT and the clinical evolution of CNMP, the subjects employed a variety of methods to promote psychological flexibility, such as exposure-based techniques, metaphors, mindfulness, and training activities compared to pharmacological treatment. The results showed that ACT is a cost-effective treatment compared to recommended medications .Our results also found that the statement related to relaxation or meditation as a means of distancing oneself from pain and reducing suffering is in line with the results of studies on cognitive therapy and mindfulness-based stress reduction (MBSR), which comprises a state of awareness that has been characterized as non-elaborative, non-judgmental present-centered awareness and a form of acceptance and trust in one’s own experience; these studies have also reported reduced pain and physical well-being .Expert patients prioritized, regarding physical activity, evidence-based recommendations to prescribe different types of exercises for the management of CNMP. Although a wide variety of exercises are recommended, it is important to take into account factors such as the intensity, duration and amount of the exercise, as well as prescribe individualized exercise to improve adherence and achieve good outcomes ,47. The The evidence presented in the narrative review of Pumar-Méndez et al.  suggestsThe expert patient opinions regarding the prioritized recommendations on health assets highlight the benefits of the asset approach for the population and the effective practices that serve as a strengthening of its capacities that can serve for a better autonomy. The importance of identifying health assets  as a strategy lies in the fact that they can be a resilience factor for disease exposure and furthermore can be a positive health entity in their own right, with a focus on quality of life and well-being, necessary to promote physical, mental and social health. Another inherent idea is that of asset mapping, whose technique is based on the search for community capacities, using individual and organizational resources in order to achieve better health management ,34,36.The health assets model provides a health perspective that encourages people to reorient their gaze to the context and focus on what improves health and well-being, strengthening their decisions about the root causes of their health problems. The recommendations of this dimension, incorporated into the multimodal intervention program, favor this line of action ,49,50.To ensure patient satisfaction and lower risks, it is essential that health professionals and researchers work together to translate clinical outcomes into value-based healthcare. Moreover, care must be personalized, and each patient’s personal situation must be taken into account to ensure that the health professional and the patient address health problems jointly from both a practical and an emotional perspective.Our research on chronic pain has as its main strength the use of an active participatory methodology to prioritize the recommendations of the best evidence found in the review of the scientific literature. However, our manuscript also has some limitations, such as not developing a comprehensive systematic review of the recommendations. Therefore, here we aim to show the search strategy and the most important findings, with the review being itself separately dealt with and published due to its remarkable length.This article also does not focus on the applications and concrete interventions to be developed from these recommendations, but the research group of this paper is working on the development of intervention programs and their evaluation, including a clinical trial to evaluate the effectiveness of a mobile application based on these recommendations.The methodology used has the advantage that the opinion and experience of a nominal group provides higher quality compared to that of a single expert, but it must be taken into account that the bias of the participants due to their cultural background, age and gender, may have an impact in some cases. For this reason, the choice of experts was careful, inviting groups with a certain homogeneity. The use of the modified Delphi, called conversational or “face-to-face” Delphi, allows each participant to express him/herself freely, but also implies the possibility that some may be tempted to join the score closest to that of the total group, without their own argument. One of the limitations of this technique is that the results depend on the accuracy of the questions. That is, there must not be any doubt about their contents because the interpretation must be unique and real.The length and wording of the sentences must be estimated and assessed. The greater the number of words in a question, the greater the possibility of error in its interpretation. To mitigate this situation, the methodology used incorporated two members of the research team, one as a moderator/informant and the other as an observer, thus minimizing the aforementioned risk.The study focuses on those treatments for chronic pain available in the primary care setting. The interventions by invasive technique, are performed in the hospital setting in the pain units and will be derived if after 6 months of treatment and adequate follow-up with a comprehensive treatment plan the intensity of the pain and/or functionality have not reached the objectives, then it should be considered as a chronic pain picture of difficult control. In our health system, for the proper management and treatment of Chronic Pain, it has been proposed to integrate care into multidisciplinary teams  within a pain care network; it would be an integrated network of services that guarantee a continuous care that would include, in addition to a Hospital Pain Treatment Unit, other specialized units of the same hospital or a different one, of different complexity, as well as other health resources such as Primary Care, social and socio-sanitary services. For its development, resources are needed, as much as protocols that guarantee the continuity of care and clinical integration of care teams along with information systems.The results of this study are consistent with the reviewed literature and the expert patients’ knowledge and ideas for the treatment of CNMP.Based on the results of the first phase of the study, a multimodal therapy application was designed for use in mobile devices. A clinical trial was then carried out to evaluate the effectiveness of a personalized intervention program using the mobile device to improve self-management and self-care at home. The aim was to assess the effectiveness of the application in reducing catastrophizing behavior, acceptance, emotional distress, and symptoms in people with CNMP.Finally, we can say that chronic pain is one of the major problems that public health systems have to face and that the response that these systems give is very important and should be considered from a multidisciplinary and person-centered approach. Thus, in addition to the necessary individualized pharmacological treatment, other interventions focused on the psychological aspects of pain are necessary, favoring a response of acceptance and centered on values, but also interventions that include recommendations on physical activity and the strengthening of health assets.A central element of our reflection of the participatory action research strategy is the path that we must walk together, both health professionals as well as patients and health institutions are to be an active part of the process, including in the clinical pathsheet shared decision making, respect, humanization of care and personalization of treatments that best suit the needs of the patient, in order to improve quality of life and self-management of chronic pain.The results of this study may contribute to the implementation of new policies for the management of people with chronic pain in primary care, being of interest not only at the community level but also for health professionals who care for these patients. High quality clinical practice guidelines and clinical trials have been found in relation to pharmacological and non-pharmacological treatments for the coordinated management of patients with chronic pain. However, more research and resources are needed in primary care to provide more efficient and effective care with the best available evidence.


Upon their first presentation, 25.5% of patients had experienced drug-related side effects due to prolonged medication. Only 50% of patients were compensated by the universal health coverage (UHC) system. Seven patients spent ≥ 50 million rupiahs and eight patients had already lost their jobs. In conclusion, early contact with a neurosurgeon contributes to better management of TN, both for the patients and healthcare system in Indonesia. A refined understanding of TN nature is still needed in this country.Trigeminal neuralgia (TN) is a debilitating neuropathic pain involving the fifth cranial nerve. There has been no study investigating the clinical and socioeconomical characteristics of patients with TN in Indonesia. A total of 100 patients were included in this study. Symptoms indicating a later stage of the illness, namely, involvement of all the trigeminal nerve branches, numbness, and concomitant persistent pain, were the common presentations found in our cohort. Only one TN diagnosis was made by a general practitioner (GP). None were immediately referred to a neurosurgeon following their diagnosis. Access to our clinic took as long as 4.7 ± 5.1 years (mean ± SD) from the onset. Older age was a significant predictor of an increased likelihood of not knowing their illness upon the referral (21.9%,  Trigeminal neuralgia (TN) is a neurologic disease characterized by a sudden and triggered-bout severe pain in the sensory area of the fifth cranial nerve . Due to Since first described in 1756, treatment methods of TN have been continuously developing. One of the most significant changes was the establishment of surgical treatment of TN. The procedure, called microvascular decompression (MVD), was popularized by Peter Jannetta and has been the only definitive treatment of TN to date. The pain resolution after MVD is expected in more than 76% of patients, even at 10 years following the surgery . FurtherIn 2014, Indonesia, a developing middle-income country, introduced its novel universal health coverage (UHC) system, covering more than 203 million people . Also, wAn established epidemiological study is a vital foundation for clinical and public health practices. This basis is the gap of knowledge in achieving the utmost management of TN in Indonesia. Through epidemiological study, diagnostic accuracy can be improved and risk factors, disease progression pattern, and burden among the affected population can also be identified , 14. ThiConsenting patients diagnosed with TN by the International Classification of Headache Disorders-3rd Edition (ICHD-3) criteria were enrolled in this study between April 2014 and January 2021. Consecutive sampling was employed. All of them were attending the Indonesian National Brain Center neurosurgery clinic in Jakarta, Indonesia.This study has been done with prior written consent after an information sheet has been provided to all the subjects. Approval by the Indonesian National Brain Center Hospital Ethics Committee was obtained.Data were collected through a checklist-guided interview by an attending neurosurgeon (MP), which consisted of the socioeconomic, demographical, and clinical characteristics of patient. Prior medical consultation and treatment concerning the facial pain were also noted including who made the diagnosis, frequency and economic burden of prior treatment, its effect, and knowledge of patient with respect to their illness. The pain history was also collected: onset, duration, side of pain, trigger, frequency, pain quality, severity, and progression. Effect of TN on the social-economical domain of patient was also documented. Data from electronic medical record (EMR) of patient was also included as an addition.U, Spearman's, Pearson's, and linear regression tests were used accordingly. A p < 0.05 was considered to indicate a statistically significant association or correlation.Statistical analyses were conducted by independent physicians in R statistical environment (version 1.3.1093). The socioeconomic and clinical characteristics of patient were descriptively presented. The mean was expressed with ±SD, while the median was expressed with interquartile range (IQR) (first quartile to third quartile). The Shapiro–Wilk test was employed for normality testing. The chi-squared, Fisher's exact, Mann–Whitney n = 22/100) either had less than a high-school diploma or illiterate and 90% of patients (n = 90/100) lived within the island. A total of 90 patients  of the cohort were head of the family and 24% of patients (n = 24/100) were full-time workers. Hypertension was found in 42 patients , where more than half patients  were females. No multiple sclerosis was identified and 10 patients  were smokers.A total of 100 subjects were included, with some variables were missing for some of patients. The demographical data are given in n = 51/97, 52.6%), with involvement of all  the trigeminal branches being the most common to be seen in our cohort . The patients with episodes of paroxysmal pain mostly experience 2–10 episodes of daily pain , with a duration of 2–30 mins seen in 57.1% of patients (n = 52/91). A total of 77 patients  complained of having paroxysmal pain lasting more than 2 min, which was significantly associated with a longer duration of illness .The right side was most commonly affected , even though only two of them had undergone invasive procedures (one patient underwent MVD and one patient underwent percutaneous radiofrequency rhizotomy). However, 30% of patients with TN with numbness had a previous history of ischemic stroke, which was statistically significant  vs. 3% in patients with TN without numbness. The mean duration from the onset was longer among patients with numbness (5.3 vs. 4.6 years), although it was not statistically significant. Numbness in any division of trigeminal nerve was observed in 28 patients (n = 71/99) were having severe pain according to verbal rating scale (VRS) classification. A total of 40 patients  had either severe pain without any relief with medication or not adequately controlled by medication [Barrow Neurological Institute (BNI) pain scale IV or higher]. Pain progression in terms of frequency and severity was seen in 76.5 and 74.7% of patients, respectively. An increase in severity and frequency was significantly associated with one another . A progression in pain frequency was significantly associated with younger age . However, younger age was not significantly associated with a progression in the pain intensity and no other clinical or socioeconomical factors were significantly associated with pain progression. In 40.4% (n = 40/99) of patients, a period of complete remission for at least 2 weeks was seen.n = 99/100) of the diagnoses were made by specialists at a secondary or tertiary healthcare facility, with most of them  were made by a neurologist. Even though 56% (n = 56/100) of all the patients had a previous history of consultation with a general practitioner (GP) at a primary healthcare facility, only one patient was diagnosed by them. Before referral, 31% of patients (n = 31/100) had more than four consultations with a healthcare professional. Even though, 43 patients  of the cohort had a previous visit with a neurosurgeon and none of them were immediately referred to a neurosurgeon upon diagnosis  were referred 10 years or longer after the pain onset. In total, 37 of our patients  who had ≥ 20 years of life expectancy (≤ 51 years) had a mean duration of 5.6 years from onset to first contact with our clinic, which is 0.9 years longer than the entire cohort, although it is not statistically significant.In total, 99% (iagnosis . The mean = 21/96) of the cohort did not know their diagnosis. The logistic regression analysis was performed to ascertain the effects of demography, clinical characteristics, and previous consultation factors. The model was statistically significant  and increasing age was significantly associated (p = 0.018) with an increased likelihood of not knowing their diagnosis.At the first contact in our neurosurgery clinic, as much as 21.9% . Five patients  had no previous history of medication for pain relief. More than a quarter patients  had already experienced drug-related side effects upon referral. In total, 24 patients  had a previous history of invasive procedures, with percutaneous radiofrequency rhizotomy being the most frequent . Previously prescribed drugs and invasive procedures performed for pain relief are given in n = 6/99, 6.1%) reported complete relief of pain from previous treatment. Most of them only had partial pain relief , while 22 patients  had no resolution and 13 patients  experienced worsening of pain.Carbamazepine was the most prescribed drug among the patients initially treated with medication  reported significant disturbance in work productivity, with 11 patients  losing jobs due to the facial pain. In total, 52 patients  reported no effect on working productivity, while 26 patients  complained of decreased work productivity. Effect of pain on work was significantly associated with the previous treatment outcome . Five patients  who lost their jobs reported pain worsening as previous treatment outcomes.A total of 13 patients (n = 48/96) in our cohort. Among the UHC-uncovered patients, 31 patients  had spent more than 5 million rupiahs  and 7 patients  spent more than 50 million rupiahs  for their treatment. There was a moderate, positive correlation between health expenditure and duration from onset to referral, which was statistically significant .The coverage ratio by the Indonesia UHC scheme was only 50% . This difference may be related to the low prevalence of multiple sclerosis (MS) in Indonesia and other Asian populations compared to the Caucasian population . BilaterInvolvement of all the trigeminal nerve branches was distinctly the most common presentation. It is contradictory to many previous findings, which stated that only the second and third trigeminal nerve branches were affected in most cases , 21, 22.Moreover, we encountered a surprisingly high proportion (29%) of patients who complained of numbness in the sensory area of the trigeminal nerve. It was presumably another sign of progression of TN observed in our cohort. Numbness has been previously depicted as a sign of deteriorated TN in several studies –26. WithFurthermore, paroxysmal pain lasting more than 2 mins was documented in 35.7% of patients. Haviv et al. postulated that more prolonged paroxysmal pain is related to the duration of the illness , a pattePoor recognition of TN among patients and physicians is an issue that we faced in supporting an ideal healthcare system. Poor recognition of their illness from the side of patient is a barrier for medical practitioners in providing the necessary medical services at proper timing. Almost a quarter of our patients did not recognize their illness at the first contact in our neurosurgery clinic. Older age was identified as an independent risk factor for lack of recognition of their disease in this study. Previous studies have shown that literacy of a person on their disease is crucially determining how they cope with pain and affecting their treatment outcome –31. Our The financial aspect of managing TN is remarkably worrisome in our country. In our cohort, the UHC covered only 50% of patients. This finding was contradictory with the national data of coverage of the system, which has been reported to reach 82.51%. We found no explanation for this matter, as all the expenditures were supposed to be covered, including dental and oral-maxillofacial surgery treatment . Since 1All of the issues we encountered here, namely, advanced TN at initial presentation, underdiagnosis by GPs at primary healthcare facilities, poor disease knowledge among patients, and high socioeconomic burden, points to ineffective management of TN at a public health level. The shortage of neurosurgeons and an unequal geographical distribution are issues that limit neurosurgical access for patients with TN. According to the Indonesian College of Neurosurgeons, our country has a ratio of one neurosurgeon for every 687.5 thousand people, compared to one for every 60–80 thousand people in developed nations . More thThe UHC stakeholders must provide at least one comprehensive consultation with a neurosurgeon upon diagnosis. A consensus when to perform an MVD must also be reached. According to a study by Linskey et al., we advocate that all the patients with TN should immediately be referred to a neurosurgeon upon diagnosis. This would allow for judicious surgical decision-making including considerations on risks and appropriate timing . We beliComplex MVD surgery, such as in cases such as vertebrobasilar dolichoectasia, must be conducted centrally at a national referral center such as ours and a clear referral pathway must be constructed by the UHC stakeholders. The current system seems to underutilize our resources to perform complex MVD surgeries. Regionalization for simple MVD cases is ideal, but an unequal distribution of neurosurgeons, surgical instruments, and MRI facility prevents the realization of such schemes . We beliIn this study, we present a clinical and socioeconomical landscape of patients with TN in a developing country, with unusual features of disease progression and a high socioeconomic burden. The challenges and lessons learned at a public health level can be applied to other developing countries, allowing them to design effective healthcare schemes for comprehensive management of TN. However, differences in geographical barriers and healthcare systems must be considered while interpreting our results and opinions.In conclusion, we presented the characterization of TN in Indonesia including the impact and challenges we faced at social, economic, and healthcare system aspects. However, it was only conducted in a tertiary healthcare setting, making our findings may not be representable to all the populations with TN in Indonesia. Our sample size was also limited. A further study was conducted at every healthcare facility level, with larger sample size, using validated instruments, assessing deeply on its health economy domain, including follow-up until the postoperative period is still needed. Current system in Indonesia has enabled an ideal scheme for management of TN to be applied, yet its realization remains a challenge to be addressed.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Indonesia National Brain Center Ethical Committee. The patients/participants provided their written informed consent to participate in this study.MP, AS, and PA contributed to the conception, design, and acquisition of the study. MP, PA, and TI conducted the data analysis and wrote the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version of the manuscript.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Abdominal surgery is one of the most definitive and mainstay treatment options for abdominal pathologies in clinical practice. Acute postoperative pain is a major challenge in the postoperative period. Although opioids are commonly used for analgesia after major abdominal surgeries, they can lead to side effects, such as nausea and vomiting, constipation, pruritus, and life-threatening respiratory depression. Regional anesthetic techniques are commonly used to prevent or minimize these side effects. The objective of this meta-analysis is to assess the effectiveness of erector spinae plane block (ESPB) and standard medical (no block) pain management after major abdominal surgeries.We searched for articles reporting the results of randomized controlled trials on ESPB and no block in pain control published before May 2021.The systematic search initially yielded 56 publications, 49 articles were excluded, and seven randomized clinical trials were included and analyzed. We extracted the data on postoperative opioid consumption, the efficacy of pain relief, time to the first opioid demand, and the rate of postoperative complications in the ESPB group and no block group.Opioid requirement and time to first analgesic request were significantly reduced in the ultrasound-guided ESPB group, but pain scores, nausea, and vomiting did not differ significantly after pooling the results of the block and no block studies. There were no reports on serious complications related to ESPB. Abdominal surgery is a common and definitive treatment option for abdominal pathologies in clinical practice. Acute postoperative pain is a major challenge in the postoperative period and is often not optimized. Inadequate perioperative pain management may result in complications such as delayed mobilization, nausea, ileus, prolonged hospital stays, and the development of chronic pain syndromes . A U.S. Therefore, to prevent or minimize these side effects, regional anesthetic techniques are commonly added to postoperative pain management .Although epidural anesthesia can provide effective pain control after major abdominal surgeries, postoperative hypotension caused by epidural block, and hypocoagulability are frequent concerns .Regional interfascial plane blocks recently introduced into clinical practice can improve the quality of postoperative pain control. Erector spinae plane block (ESPB) was first performed and described by Forero “as a successful interfascial plane block for thoracic neuropathic pain”  and is nESPB is performed by administering local anesthetic in the erector spinae plane and produces an effective and wide sensory block in the ipsilateral thorax .ESPB has been shown its value and efficacy in acute as well as in chronic pain management , 9.Since the number of ESPB performed for postoperative analgesia in recent years is increasing rapidly, we decided to conduct a systematic review.The primary objective of this systematic review and meta-analysis is to compare postoperative opioid consumption between ESPB and no block. The secondary objectives include the efficacy of pain relief, time to the first opioid demand, and the rate of postoperative nausea and vomiting.We developed a protocol with the inclusion and exclusion criteria for relevant articles. The method of analysis was established and approved by all authors. This is a meta-analysis investigating ESPB vs. No block in patients who underwent abdominal surgeries. This quantitative systematic review was conducted in accordance with the PRISMA guidelines.Using PubMed, Google Scholar, and the Cochrane Library, we conducted a search for relevant articles available in these databases from their inception to May 2021. The search terms included the combination of “erector spinae plane block,” “erector spinae block,” “ESP block,” “ESPB” AND “abdominal surgery,” “abdominal cancer surgery.” We searched the journals and references for all articles relevant to the study. Neither ethical approval nor patient consent was required.Inclusion Criteria:1) Randomized controlled trials (RCT);2) Age—18 years old and older;3) ESPB  in acute pain management after abdominal surgery and no block pain management methods assessed using the standard scales, VAS  and NRS .4) Both open and laparoscopic abdominal surgery.Exclusion Criteria:1) Non-RCTs: case reports or series, editorials2) Cadaver studies, retrospective studies, technical reports.Patient, Intervention, Comparison, and Outcomes (PICO) Criteria:We included studies that fit the following criteria:Population: Adults (>18 years) undergoing abdominal surgeries;Intervention: bilateral erector spinae plane blocks for abdominal surgeries (ESPB);Comparator: No block or placebo (sham);Outcomes:Primary—to compare ESPB and no block in opioid consumption during the first 24 h following surgery;Secondary—comparison of pain scores after surgery ; time to first rescue opioid administration; side effects of opioids (nausea and vomiting); side effects and complications related to ESPB including local anesthetic systemic toxicity (LAST).Studies to be included: randomized controlled clinical trials.Ultrasound-guided ESPB was performed in the interventional group, whereas the control group received a placebo or “no block”.Comparisons between the groups were made. The main outcome of the meta-analysis was to compare opioid consumption during the first 24 h following surgery. The secondary objectives included comparing pain scores after surgery, time to first rescue opioid administration, side effects of opioids (nausea and vomiting), and other complications if any.Three reviewers independently screened the titles and abstracts to identify articles that meet the review inclusion criteria.We extracted and entered data in a systematic review data table. The extracted data included the following rubrics: authors, reference, year of publication, surgery type, sample size, time of the block, and adverse events  –14. We cThe systematic search initially yielded 56 publications, of which 49 articles were excluded. A total of 373 patients [187 patients in ESPB and 186 patients in the control (no block) group] undergoing abdominal surgeries from 7 randomized clinical trials were analyzed . The dathttps://www.mdanderson.org/)  groups. In particular, the studies reported the total pethidine consumption , 16, theon.org/) .2 = 82%) and that is significant . The total number of individuals in each group is 121. In addition to the above five studies, Prasad et al.  was lower than in the control group ; however, this study was not included into our meta-analysis because it did not report the sample standard deviation for the ESPB group.For the total opioid consumption meta-analysis, we used the random-effects model with a standardized mean difference since the studies reported the use of multiple different opioids. The study heterogeneity is high  did not show a significant pain score reduction (VAS/NRS) at the first 24 h following the surgical procedure. Another finding is that ESPB was better than no block in assessing the time to first demand rescue analgesia. Finally, ESPB was not better than no block in reducing the rates of postoperative nausea and vomiting.Several recent clinical trials and systematic reviews demonstrated the positive effect of ESPB in non-abdominal surgeries in reducing early postoperative opioid requirement and time to first opioid requirement . ESPB caThe following drugs and methods are usually used for postoperative pain control: non-steroidal anti-inflammatory drugs with opioids, and regional techniques, such as ESPB. Combining these drugs can lead to an additive effect increasing the effect of individual analgesic agents and reducing their side effects. Unfortunately, in many cases, drug therapy is insufficient to maintain appropriate postoperative analgesia; therefore, regional techniques, such as ESPB, are commonly used.Previous trials and our meta-analysis have demonstrated that ESPB reduced postoperative opioid requirements . AlthougThe current opioid crisis requires new approaches allowing the reduction of opioid use. Moreover, despite the fact that opioids have been shown to be one of the most effective approaches for pain management, the majority of patients report incomplete pain relief and side effects after surgery. Laparotomy is known to induce intense nociceptive stimulation by surgical injury to the skin, parietal and visceral peritoneum, and visceral structures .Erector spinae plane block (ESPB) is a type of facial plane block in which local anesthetic is administered in the plane located between the erector spinae muscle and thoracic transverse process . ESPB blNo major complications related to ESPB were reported. More trials and data on safety and complications related to ESPB are needed . AlthougESPB has low risks of complications associated with hypocoagulable states, which might be an issue for epidural anesthesia. Because there are no major vessels in close proximity to the erector spinae plane, the risks of intravascular injections of local anesthetics or hematoma are lower than in other regional anesthetic blocks .Nevertheless, like other types of interfascial plane blocks, especially if high volumes of local anesthetics are used, LAST recognition and management algorithms should be exercised . For exaThe use of lower concentration and high volume solutions was proposed to minimize the risk of LAST; a higher volume of local anesthetics improves the efficacy of the block by covering more segments, whereas low volume theoretically reduces the risks of LAST . The ideAlthough the use of low local anesthetic concentration can reduce the risks of LAST, more opioid anesthetic might be required to provide sufficient pain control. It can, in turn, increase the risks of opioid-related side effects . The incidence of nausea and vomiting after surgery was reported to be significantly lower in the group with high bupivacaine concentration, possibly due to reduced tramadol administration .A major limitation of this meta-analysis is that there was a limited number of matched clinical trials focused on ESPB in pain control after abdominal surgeries. The lack of significance is then attributed to inadequate amounts of studies included in the analysis. The second limitation is due to the heterogeneity of the structure, style, and rubrics of the studied and published results. The next major limitation is high heterogeneity in types and extends of surgeries  and approaches . Another limitation is that our literature search might have failed to find all publications related to the review objectives.This meta-analysis demonstrated that opioid requirement and time to first analgesic request was significantly reduced in the ultrasound-guided ESPB group, but pain scores, nausea, and vomiting did not differ significantly after pooling the results of the block and no block studies. No serious complications related to ESPB were reported. Future RCTs with more standardized reporting rubrics are warranted to verify and consolidate the results of previous RCTs and this meta-analysis.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.DV: protocol, screening, writing, revision, and final approval. YA: statistical analysis, writing, and final approval. MA: data extraction, revision, and final approval. All authors contributed to the article and approved the submitted version.This work was supported by the Nazarbayev University Faculty Development Competitive Research Grant 2021-2023. Funder project reference: 021220FD2851.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Fibromyalgia syndrome (FMS) is a pain disorder characterized by chronic widespread pain, fatigue, and sleep disturbance, in the absence of any well-defined underlying organic disease. The exact pathophysiology and the mechanism which links different factors related to the disease is still unknown. Due to unknown precise pathogenesis, the coexistence of other diseases, and overlapping clinical features, FMS diagnosis may be laborious. Various treatment strategies are used, only a few Food and Drug Administration (FDA) approved, still we are facing challenges regarding effective treatment. Recently, medicinal cannabis has proven to be effective in chronic pain conditions such as osteoarthritis, neuropathic pain, and other non-cancer chronic pain. However, further research is needed about how the cannabinoid system works with the pain pathway. Using the fact that medicinal cannabis is effective in the treatment of chronic pain and certain rheumatic diseases, in this review, we aim to analyze the role of the cannabinoid system in fibromyalgia syndrome.We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines in searching PubMed, MEDLINE (through PubMed), PubMed Central, and Google Scholar using keywords "fibromyalgia, chronic pain, cannabis, cannabinoids, pharmacotherapy, alternative therapy" and Medical Subject Heading (MeSH) words.After applying inclusion/exclusion criteria and checking for the quality assessment, 22 articles were retrieved and used for the analysis of the role of cannabis in the treatment of fibromyalgia. The two main compounds of cannabis with analgesic and anti-inflammatory properties are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), and their ratio determines the effect on various symptoms of FMS. We included studies regarding the use of cannabinoids in the treatment of fibromyalgia, investigating the use of nabilone, dronabinol , Bedrocan , Bediol , and Bedrolite .In the era of the coronavirus disease 2019 (COVID-19) pandemic and opioid crisis, many adverse outcomes are observed in the patients suffering from FMS due to lack of any definitive treatment and promising outcomes from the known treatment options, which led to the need for effective and safer treatment alternatives.Although the studies reviewed in this article suggest that medical cannabis is a safe and effective treatment for fibromyalgia pain, several limitations regarding dosage, length of treatment, adverse effects, long-term follow-up, and dependence needs further investigation. Fibromyalgia syndrome (FMS) is a pain disorder with an estimated prevalence of 5-7% in the world, with a mean prevalence among the American and European populations of 4% . It is mThe syndrome is characterized by chronic widespread pain, fatigue, and sleep disturbance. The exact pathophysiology is still unknown, but the most accepted pathology is the alteration of central pain pathways, which results in hyperalgesia. There is also evidence that supports the role of mast cells in musculoskeletal pain and central sensitization. The mast cells can mediate the activation of microglia through the production of cytokines like interleukin 1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor (TNF) alpha. Despite all the known facts, the mechanism that links different pathological features including stress, central sensitization, and dysregulation of innate and adaptive immune response is still unknown, making the treatment approach more challenging .A recent study also showed a link between autoantibodies and FMS, as one-third of FMS patients with xerostomia tested positive for Sjogren's syndrome biomarkers and the majority of them were positive for one or more tissue-specific autoantibodies. The diagnosis of FMS is also challenging due to the coexistence of other conditions. FMS is rarely a stand-alone diagnosis, as most patients meet the criteria of other overlapping chronic pain conditions or mental disorders. Once diagnosed, the treatment is also challenging. Various treatment options are available including memantine, naltrexone, tapentadol, duloxetine, palmitoylethanolamide tablets, and cannabinoids. But none of them have 100% promising results .Formulations using cannabis have been used in clinical settings to study its efficacy in reducing pain when traditional options have failed . CannabiFinally, despite considerable uncertainty regarding the mechanism of action and its exact role in the management of pain and non-pain symptoms of fibromyalgia, medical cannabis has become a very important focus for research and controversies in the last few years but it also represents hope for many patients . In thisMethodsThe Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) was used for this study . We idenResultsA total of 363 articles were retrieved after title screening. A total of 250 less relevant articles were excluded, and 163 articles were retained. A total of 114 more articles were excluded after checking the eligibility criteria and 49 articles were retrieved and checked for the quality assessment using AMSTAR  for systematic review and meta-analysis, Cochrane risk bias assessment tool for clinical trials, Newcastle-Ottawa Scale for observational studies, and SANRA  for review articles, and 49 final full-text articles were retrieved for study. A total of 25 more articles were excluded after reading the full text, assessing the quality appraisal and relevance related to the research question. Finally, 22 articles were retrieved for study. Figure DiscussionFibromyalgia (FM) is a syndrome characterized by chronic pain with multiple tender points, increased pain sensitivity, and other systemic symptoms like cognitive dysfunction, sleep disturbance, anxiety, chronic fatigue, and depression, in the absence of any well-defined underlying organic disease . In mostWith the recent coronavirus disease 2019 (COVID-19) pandemic situation, the patients with FM syndrome reported adverse mental and physical outcomes, and this exacerbation of symptoms can be related to the increasing level of anxiety, economic hardships, and social isolation , which lPathophysiology and DiagnosisThe etiology of this disease is still unknown, and the research in this field has expanded considerably, exploring the genetics, immune system, autonomic system, inflammatory response, neurotransmitters, and psychological factors . InitialIn addition to the stress regulation and inflammatory response, the HPA axis and the sympathetic adrenal-medullary axis are also involved. Some studies in animals also suggest the involvement of T-cells autoimmune response in hyperalgesia; nevertheless, the results of the studies indicating the changes specific to T-cell are inconclusive . One intIt is also hypothesized that lack of endocannabinoids activity is the possible pathophysiology of fibromyalgia ,9,11, anThe exact diagnosis requires certain guidelines that reflect not only the classification criteria but also explain the pathogenesis. Due to still unknown pathophysiology, the diagnosis is even more challenging and about 75% of patients remain undiagnosed ,9. As itTreatment StrategiesVarious pharmacological and non-pharmacological therapies can be used for the treatment of FM. Pharmacological therapy is primarily aimed at lowering the level of pro-nociceptive neurotransmitters. There are only a few drugs approved by the Food and Drug Administration (FDA) for FM: pregabalin, duloxetine, and milnacipran . As therDue to the complex nature of the disease, a multidimensional approach is proposed, including non-pharmacological methods in addition to pharmacological treatment, which include acupuncture, cognitive behavioral therapy, hyperbaric oxygen therapy, mindfulness, massage, and transcranial magnetic stimulation. Although outcomes are encouraging, further studies are required to assess the effectiveness of these methods alone or in combination .New treatment options are under investigation: mirtazapine, an alpha-2 antagonist with serotonergic and noradrenergic effects, milnacipran, a serotonin-norepinephrine reuptake inhibitor, and opioids. The mentioned treatments have been assessed for effectiveness, but the results are so far controversial. The cannabis plant seems to be a promising tool to fight fibromyalgia chronic pain [Cannabinoids for FibromyalgiaGiven the fact that we are in the era COVID-19 pandemic and an ongoing opioid crisis, there is an absolute need for effective and safer treatment alternatives for chronic pain syndrome including FM. With a high margin of safety and proposed regulatory effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) on major endogenous pain circuitry systems, cannabis is emerging as a promising alternative treatment option for the management of chronic pain .Regarding the complex function of the endocannabinoid system in pain modulation, it is hypothesized that lack of endocannabinoids activity is among the underlying pathophysiology of FM but there is no clear evidence to support this assumption ,9,11,15.The analgesic effects of cannabinoids and their ligands are primarily mediated by the CB1 receptor via inhibition of presynaptic gamma-aminobutyric acid (GABA) and glutamatergic transmission, which suppresses neuronal excitability . AlthougThe results of several old studies showed certain limitations as most of them involved the use of nabilone and dronabinol (a synthetic delta-9-THC), and concluded with the certain incidence of noticeable adverse effects and low tolerability depending upon the patient’s conditions and loss of follow-up with most of the patients ,15,16. HIn one other recent study, nabilone and dronabinol showed improvement in pain and anxiety in several randomized controlled trials and meta-analyses. Tetrahydrocannabinol to cannabidiol ratio (THC:CBD) therefore determines the overall effect. It also concluded that manipulating the endocannabinoid system is gradually emerging as another fascinating strategy for treating pain and suggested future research into the clinical utility of endocannabinoid metabolism manipulation in FMS .Therapeutic Use of Cannabis for FibromyalgiaFindings regarding the use of cannabinoids in the treatment of fibromyalgia consisted of several studies, investigating the use of nabilone, dronabinol, a synthetic analog of THC, Bedrocan , Bediol , and Bedrolite  . The cliIn one experimental study designed to examine the effect of adding medical cannabis to analgesic treatment, which consisted of 38 patients treated for three months with standard analgesic therapy with minor improvement in the symptoms, treated with medical cannabis therapy for a minimum of six months, which resulted in higher improvement in all patient-reported outcomes (PROs), which included Fibromyalgia Impact Questionnaire (FIQ), visual analog scale (VAS), Oswestry Disability Index (ODI), and lumbar range of motion (ROM), which was recorded using the modified Schober’s test .Another study, consisting of 20 patients carried on the same principle but different cannabis compounds, showed the complex behavior of different inhaled cannabinoids compound in chronic pain patients with just small analgesic responses after a single inhalation. Four different cannabis varieties were tested including Bedrocan , Bediol , Bedrolite , and a placebo variety without any THC or CBD. The study results showed that none of the treatments had an effect greater than placebo on spontaneous or electrical pain responses, although more subjects receiving Bediol displayed a 30% decrease in pain scores compared to placebo. It also showed antagonistic pharmacodynamic interactions of THC and CBD. So further studies are needed to determine long-term treatment effects on spontaneous pain scores, THC-CBD interactions, and their effects on pain relief. In this study, two experimental pain tests were performed, the electrical pain test and pressure pain test; pressure pain threshold increased significantly in patients treated with Bedrocan and Bediol. In addition, Bediol had notably greater effects than Bedrolite so significantly more patients responded to Bediol. Bedrolite, a cannabis variety with a high CBD content, was devoid of analgesic activity in any of the spontaneous or evoked pain models .About further studies, one study consisting of 367 patients conducted to investigate the safety and efficacy of medical cannabis in fibromyalgia was conducted on patients who were willing to answer the questionnaire in a specialized medical cannabis clinic between 2015 and 2017. It concluded that medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms with certain limitations like standardization of treatment compounds and regimens, which require more research. This study included patients with six months follow-up and the response rate was 70.8%. The pain intensity reduced from a median of 9.0 at baseline to 5.0 on a pain scale 0-10 (p < 0.001), and 194 patients (81.1%) achieved treatment response. The most common adverse effects were mild and included dizziness, dry mouth, and gastrointestinal symptoms .With previous knowledge on two different compounds (Bedrocan and Bediol), another study carried out to study further outcomes, included 102 FM patients to assess any clinical improvement following the addition of medical cannabis treatment (MCT) to the stable (≥ three months) standard analgesic treatment of FM patients. Patients were prescribed two oil-diluted cannabis extracts: Bedrocan , and Bediol . FM severity was periodically assessed using the Fibromyalgia Impact Questionnaire (FIQ), Fibromyalgia Assessment Scale (FAS), Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score, Pittsburgh Sleep Quality Index (PSQI), and Zung Depression and Anxiety Scales. During the study, patients were allowed to reduce or stop their concomitant analgesic therapy. Finally, 50% showed a moderate improvement in anxiety and depression; besides, analgesic treatment was reduced or suspended in 47% of the patients. In general, only one-third experienced mild adverse events. Overall, it showed that adjunctive MCT offers a possible clinical advantage in FM patients [In another study, a double-blind randomized placebo-controlled clinical trial consisting of 17 women that were conducted for eight weeks to determine the benefit of THC-rich cannabis oil on symptoms and quality of life, concluded that cannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. The Fibromyalgia Impact Questionnaire (FIQ) was applied at pre- and post-intervention moments and in five visits over eight weeks. After the intervention, the cannabis group presented a significant decrease in FIQ score in comparison with the placebo group .A study on the effect of cannabinoids on chronic pain patients including 132 FM patients out of a total of 751 patients with chronic pain with other underlying conditions, also showed promising results, but the percentage of patients with fibromyalgia included in this study is 17.6%, which is very low to make a relevant assumption. Nevertheless, results concluded over patients were promising with improved pain scores over 12 months. Moreover, the medical cannabis (MC) treatment course in this study was not associated with increases in the frequency of undesired adverse events, but rather decreased the frequency of headaches, fatigue, feelings of anxiety, and nausea .Recently a retrospective, open-label case series consisting of 38 patients was conducted to study the efficacy and adverse events (AEs) of short- and long-term MC treatment for FM concluded that MC may be used as an alternative treatment for patients with FMS who are unresponsive to conventional therapy. However, its application may be limited by the incidence of non-serious adverse effects. The study was conducted for 12 months with follow-up at 1, 3, and 12 months. The results were interpreted based on certain scales including Numerical Rating Scale (NRS), Oswestry Disability Index (ODI), Hospital Anxiety and Depression Scale (HADS), Widespread Pain Index (WPI), and Severity Score (SYS). The most common side effects were mental confusion, dizziness, nausea/vomiting, and restlessness/irritation .All these studies showed the significant advantage of MC in treating pain in patients with FMS with a few non-serious adverse effects. Medical cannabis appears to be a safe and effective alternative for the treatment of fibromyalgia symptoms.As FM is a syndrome of symptoms with still not completely known pathogenesis, it might pose additional difficulty in treating it. Also, with the recent advancements and studies regarding lack of endocannabinoid activity as a possible cause of the disease process, cannabis is considered a future hope for treating FM syndrome as it has shown a significant advantage in treating this condition with very few adverse effects. Future studies are still needed to assess long-term benefits, THC-CBD interactions, and their effects on pain relief, to determine and standardize treatment regimens, to assess long-term benefits, dose-response relationship, and dependence.LimitationsThere are certain limitations in our study, as we only used articles in the English language, conducted only on humans, and published in the last five years; hence, certain valuable studies could have been excluded.Our main aim was to assess the safety and efficacy of cannabinoid compounds for the treatment of FMS. At this point, the data suggest that the use of cannabinoids and cannabis carries limited side effects in the treatment of FM, and they can also improve some common and debilitating symptoms associated with FM, thus making them an adequate potential treatment option, when other treatment lines have been exhausted.Ultimately, we believe that the use of cannabis and cannabinoids for pain relief in fibromyalgia has shown great potential and maybe a source of hope for those suffering from chronic pain associated with this condition, and for the physicians treating them; however, benefits need to be weighed against the harmful effects, and more research into this area should be conducted, for longer periods, to assess for long-term efficacy, adverse effects, and dependence. The ratio of TCH:CBD also seems to be an important factor in the outcome, which needs further research. So more clinical trials with long-term follow-up and study on the dose-response relationship and dependence need to be done.


Analyzed data comprised general demographics, presenting symptoms, comorbidities, spinal infection location, and amount of spinal involvement. While average age (62.4 vs. 65.0) and sex distribution was similar between the two groups, a significant diagnostic delay was noted in the control group . Patients in the no pain group were more likely IV drug abusers or have had liver failure/cirrhosis. Anatomic distribution  of the infection did not differ between the two groups, but a higher number of post-surgical infections was noted in the no pain group . E. coli and Pseudomonas spp. were more commonly seen in no pain group patients, and mortality was also higher in this group .Study design: Retrospective analysis of a single institution prospective, longitudinal database of spinal pyogenic infections. Diagnosis of pyogenic spondylodiscitis (PS) can be challenging. Although presenting symptoms are often non-specific, acute non-remitting axial back pain is the most striking feature. Nevertheless, several authors have reported on the uncommon occurrence of patients with PS without axial back pain. The aim of this study was to characterize presenting symptoms, causative agents, comorbidities, and treatment outcomes of patients presenting with painless pyogenic spondylodiscitis. A total of 214 patients diagnosed with PS were reviewed; patients were divided into two groups: patients presenting with no axial back pain ( Spinal infections represent 3 to 5% of all cases of osteomyelitis, with incidence ranging from 0.5 to 5.8/100,000 inhabitants/year ,3.Diagnosis of PS can be challenging; a significant diagnostic delay between the onset of symptoms and definitive diagnosis has been reported by several authors . PresentOnce a diagnosis of PS is established, the mainstay of treatment remains IV antibiotic therapy. In patients without neurological compromise or major spinal instability, conservative orthopedic treatment with rigid immobilization is indicated. In case of spinal instability or impending neurological deficit, surgical decompression and debridement are advised.In 2008, we established a prospective, longitudinal database for all patients with spinal infections treated at our institution [Following Institutional Review Board (IRB) approval, we retrospectively reviewed all consecutive patients with a confirmed spinal infection enrolled in a longitudinal, single-center, prospective database from January 2008 to December 2018. All patients gave their written consent at the enrolment into the database. For the current analysis, only patients with a diagnosis of pyogenic spondylodiscitis and a minimum 2-year follow-up were enrolled. A diagnosis of pyogenic spondylodiscitis was made on clinical , radiological , and microbiological  grounds. All data were collected by independent researchers not involved in data analysis or clinical care of the patients.no pain group), and patients presenting with axial low back pain (control group).For the current analysis, patients were divided in two groups: patients presenting without low back pain at diagnosis  qualified recovery, survival, and disappearance of all sign and symptoms but with a residual disability such as motor weakness or chronic pain due to spinal imbalance, spinal instability, bone destruction, residual spinal canal stenosis, (3) death, either caused by the infection or by associated comorbidities [A healed infection was considered after a complete course of antibiotic therapy (minimum 6 weeks), negative blood inflammatory markers, absent clinical findings  12 months after the end of treatment. A relapsed infection was defined as a pyogenic spondylodiscitis presenting at the same spinal level of the previous infection within 12 months. Treatment failure was defined as persistence of symptoms  and raised inflammatory markers  at the end of antibiotic treatment . Treatmebidities .2 test, while continuous variables were compared using Student’s t-test. A p level ≤ 0.05 was considered significant. Data were analyzed using the SPSS Statistics software, v23  and Microsoft Office Excel 2016 Professional .Data are expressed as mean with ranges unless stated otherwise; counts and percentages are used as appropriate. The normality distribution of the data was assessed using the Shapiro–Wilk test. Categorical variables were compared using χno pain group), while 198 patients  presented with back pain (control group). With the exception of back pain, presenting symptoms were not statistically different between the two groups  were included in our institutional database from January 2008 through December 2018. Among these, 16 patients  presented with no axial back pain at the time of diagnosis (o groups .p = 0.693), weight loss in 31.3 and 24.7% (p = 0.564), and radiating pain in 18.7 and 41.4% (p = 0.074) of the no pain and control groups, respectively. The average C-reactive protein level was also not significantly different between the two groups . The average time to diagnosis in the control group was 53 days (range 2 to 300). This was significantly longer than the diagnostic delay observed in the no pain group   .p = 0.010) and liver failure/cirrhosis (18.8 vs. 3.0%) in the no pain group. Prevalence of diabetes , immunodepression , and cancer (37.5 vs. 20.7%) was similar in the two groups. The average number of comorbidities per single patient was on average higher in the no pain group (2.5 vs. 1.8) but not statistically significant (p = 0.153)  .p = 0.936), followed by thoracic spine . In 56.2% (no pain group) and 73.2% (control group) of cases a single level infection was observed (p = 0.145). The number of multiple level infection and the extent of spinal involvement  was not statistically different between the two groups (p = 0.026).The level of the infection was more commonly located in the lumbar spine in both groups . A higher number of E. coli  and Pseudomonas  infections was observed in the no pain group.p = 0.322) [p = 0.391). The observed mortality was 12.5% in the no pain group and 6% in the control group, and this was statistically significant (p = 0.004) , while a posterior stabilization was required in 50 and 30.4% of patients in the no pain and control groups, respectively (= 0.322) . The ave= 0.004) .Even today, with modern medicine and novel antibiotic therapies available, pyogenic spondylodiscitis remains a difficult clinical diagnosis and a severe disease to the patient. Presenting symptoms are frequently non-specific . Back pap = 0.348) and WBC (p = 0.289) compared to pain-presenting patients. Furthermore, prevalence of diabetes among the two groups in our case series was also similar . Hence, we were not able to identify any specific factor related to no pain presentation in patients with PS. Therefore, maintaining a high grade of suspicion remains the most important aspect in the early identification of patients with pyogenic spondylodiscitis.Several authors have previously reported on patients with PS presenting without back pain. The percentage of no pain patients varies in the literature from 2.5 to 15%, and it was 7.5% in our case series . The mecp < 0.001). A significant diagnostic delay in the diagnosis of PS has been reported by several authors [Interestingly, no pain presentation was associated with a reduced diagnostic delay in our patients . Wang et al. have specifically looked at clinical features of patients with PS and IV drug abuse. In their report, 40% of IV drug abusers presented without pain but with neurological involvement in 61% of cases [In our case series, the prevalence of IV drug abusers was significantly higher in the no pain group . The overall mortality rate for PS is 5–10% [Arguably, the most important finding in our study was the higher mortality rate observed in PS patients presenting without back pain  does not allow us to draw definitive conclusions about this varied population of patients.E. coli and Pseudomonas isolates. Although the percentage of patients requiring surgery was similar between no pain and control PS group, mortality from PS was significantly higher in patients without back pain (12.5 vs. 6.0%).In conclusion, our study confirms previous reports that back pain can be absent in up to 7.5% of patients with PS. Patients presenting without pain are more commonly IV drug abusers or have liver cirrhosis. The average number of comorbidities per patient tends to be higher in patients without back pain. A higher number of post-operative infections were observed in these patients with a higher number of


Objective: This study was designed to investigate preoperative anxiety situations and postoperative pain degree in Chinese patients undergoing laparoscopic hysterectomy and to analyze the related factors of preoperative anxiety and the correlation between preoperative anxiety and postoperative pain to provide a reference for effective postoperative analgesia management.Methods: A total of 100 female patients undergoing laparoscopic hysterectomy were enrolled in this study and randomly divided into two groups . In group A, the patients were treated with dexmedetomidine and sufentanil for postoperative analgesia. In group B, the patients were treated with sufentanil alone for postoperative analgesia. All patients were evaluated with a self-rating anxiety scale (SAS) 1 day before the operation. The patients’ pain was evaluated using the numerical rating scale (NRS) 1 day after the operation, and data were recorded.Results: In these 100 patients, the highest preoperative SAS score was 48, and the average score was 40.99 ± 4.55 points, which is higher than the norm in China. There were significant differences in preoperative SAS scores among patients with different occupations and previous surgical experience (P < 0.05). There was no significant difference in SAS scores among patients with different education levels (P > 0.05). The postoperative NRS score of group A was significantly higher than that of group B, and the difference was statistically significant (P < 0.05). The correlation coefficients between SAS scores and NRS scores in groups A and B were 0.836 and 0.870, respectively, presenting with a significantly positive correlation.Conclusion: Preoperative anxiety is an important predictor of postoperative pain. Patients undergoing laparoscopic hysterectomy have preoperative anxiety. The degree of anxiety is influenced by the occupation and previous operation experience of the patients, and patients with higher preoperative anxiety have greater postoperative pain. In addition, we should not neglect the management of postoperative pain because of the small trauma of laparoscopic surgery, and dexmedetomidine combined with sufentanil can improve the postoperative analgesic effect. Anxiety as a disorder is defined as a neurosis characterized by anxious overconcern extending to panic and frequently associated with somatic symptoms . AnxietyPrevious studies on the correlation between anxiety and pain were mostly based on open surgery . In receThe ethics committee of Shanxi Provincial People’s Hospital approved the present study. A total of 100 female patients who underwent elective laparoscopic hysterectomy from 2019 to 2020 in our hospital were enrolled in this study. The inclusion criteria were ASA grade I-II, age 45–55 years, and a weight of 50–80 kg. The exclusion criteria were patients with chronic pain, malignant tumors, and severe complications. These patients were randomly divided into two groups: dexmedetomidine postoperative analgesia pump group (group A) and sufentanil postoperative analgesia pump group (group B), with 50 patients in each group. Eligible patients were screened 1 day before surgery and informed of the investigation protocol in written and oral form. After signing the consent form, the patients filled in the questionnaire form about their medical history, socio-economic status, and SAS . For thecis-benzene sulfonate and sufentanil were used for injection. Anesthesia was maintained with continuous infusion of propofol and remifentanil, and atracurium cis-benzene sulfonate and sufentanil were intermittently added on time and on-demand. Anesthesia was stopped at the end of the operation. The formula of postoperative analgesia pumping in group A was 1 μg/kg of dexmedetomidine, 1.2 μg/kg of sufentanil, and 10 mg of azasetron. The formula of postoperative analgesia pumping in group B was 1.2 μg/kg of sufentanil and 10 mg of azasetron. All the anesthetics were diluted with normal saline until the total volume was 100 mL. The loading dose was 2 mL, the background dose was 2 mL/h, the bolus dose was 2 mL/time, the lockout time was 15 min, and the limit dose was 10 mL/h.After the patients entered the operating room, routine electrocardiographic monitoring was performed. All patients were given total intravenous anesthesia. Propofol was used for anesthesia induction. Atracurium General information included medical insurance status, marital status, education level, occupation, and previous surgery history.The SAS was developed by Numerical rating scale is a widely used pain assessment method worldwide. It has the characteristics of high reliability and sensitivity. On this scale, a scale of 0–10 is used to mark the pain intensity of different degrees, which the patient identifies. A score of 0 represents no pain, and 10 represents the most severe pain. A score below 4 indicates mild pain (pain does not affect sleep). A score of 4–7 indicates moderate pain, and a score of >7 indicates severe pain (pain leads to an inability to sleep or waking from sleep).T-Test” in SPSS was used to compare the average values. All data were expressed as mean ± SD. The statistical significance was P < 0.05. A t-test was used to compare the anxiety status of the subjects and the Chinese norm and compare the analgesic effects of the two analgesic schemes. One-way analysis of variance was used to find the independent factors related to preoperative anxiety. Pearson’s correlation analysis was used to explore the correlation between preoperative anxiety and postoperative pain.The sample size was determined based on our preliminary data. The statistical analysis was performed using the SPSS 25.0 software. The “Summary Some demographic characteristics are also associated with a higher incidence of mental illness . Table 1P < 0.01, The results of the SAS of 1,158 average Chinese patients measured by the Scale Collaboration Group were used as the norms in China . In thisIn addition, the results of the present study revealed that for these 100 patients, the SAS score was 32–48. No patients had SAS scores lower than 30, and no patients had SAS scores higher than 50 .P < 0.01). The education level of patients had no impact on preoperative anxiety (The influence of education level (three categories), occupation (four categories), and previous operation experience (three categories) on preoperative anxiety were analyzed. The result revealed that unemployed patients had higher preoperative anxiety. The lowest SAS score in this category was 40. Patients with previous painful surgery experience had the highest degree of anxiety. The lowest SAS score in this category was 45. The patient’s occupation and previous surgical experience affected their preoperative anxiety, and the difference was statistically significant . Pearson’s correlation analysis was performed on SAS scores and NRS scores of the two groups. R values were 0.836 and 0.8709, respectively. All were greater than 0.5; that is, there was a positive correlation between postoperative pain and preoperative anxiety, and the correlation was significant. Patients with higher preoperative anxiety have stronger postoperative pain (The SAS score was 40.56 ± 4.72 points in group A and 41.42 ± 4.18 points in group B, and a ive pain .Anxiety is the most common negative emotion and mental disorder in the perioperative period. Disease, hospital environment, preoperative examination and treatment, operations, and postoperative pain may cause anxiety. The results of our survey revealed that the preoperative SAS scores of patients undergoing laparoscopic hysterectomy were significantly higher than the Chinese norm, suggesting that the patient had anxiety before the operation.In addition, the results of the present study revealed that in these 100 patients, no patient had a SAS score lower than 30, suggesting that anxiety is common in patients. The reason may be related to the fact that the subjects were all women. A related study revealed that female patients were more likely to have anxiety . AnotherThe SAS scores of all patients in this study were less than 50. The highest preoperative SAS score was 48, and the patients with SAS scores of 48 accounted for 5% of all patients . This shThere are few studies on the influence of educational levels on preoperative anxiety and postoperative pain. Lanitis revealed that  patientsThis study revealed that the preoperative SAS scores of patients with different occupations were different. The SAS scores of unemployed people, farmers, workers, and personnel of enterprises and institutions were ordered from high to low in turn, and the anxiety level of unemployed people was the highest. The difference in occupation led to the difference in income, and patients with poor financial status were more likely to be anxious.The patient’s previous surgical experience affected their preoperative anxiety. The SAS scores ranged from high to low in patients with painful operation experience, patients who have had surgery but no painful experience, in patients without operation experience. Patients with previous painful surgery experiences were more prone to anxiety, and the distressing memory of the previous operation aggravated the anxiety.Pain is an unpleasant sensation and an emotional experience caused by tissue injury or potential injury . It is aThis survey revealed that the NRS scores of both groups A and B were above 4, and the goal of postoperative pain management was postoperative pain score <3. A total of 72% of patients experienced moderate postoperative pain, suggesting that the acute postoperative pain of patients with laparoscopic hysterectomy has not been effectively controlled.Acute pain was the most common problem after surgery and has not been effectively controlled . A reporTraditional concepts believed that laparoscopic surgery has less body surface damage and less postoperative acute pain. Therefore, the postoperative analgesia needs of these patients are often ignored. The results of the study conducted by The results of this study revealed that preoperative anxiety situations were significantly positively correlated with postoperative pain degrees in patients undergoing laparoscopic hysterectomy. That is, preoperative anxiety is a predictor of postoperative pain. The higher the preoperative anxiety is, the greater the postoperative pain. This is consistent with the results of many previous studies . It is wAn important part of breaking the cycle of anxiety is to strengthen postoperative pain management. The results of previous studies revealed that physical therapy, music , psycholIn this study, dexmedetomidine and opioids were used for postoperative analgesia in patients undergoing laparoscopic hysterectomy. The degree of pain was lower in patients in group A who were treated with dexmedetomidine combined with sufentanil than patients in group B, who were treated with sufentanil alone. In group A, the scores of all patients were below 6, and in group B, the scores of all patients were below 7. This is related to the sedative, analgesic, and anti-anxiety effects of dexmedetomidine . Chen etIn summary, preoperative anxiety is an important predictor of postoperative pain. Patients with higher preoperative anxiety have greater postoperative pain. Patients undergoing laparoscopic hysterectomy have preoperative anxiety, and the degree of anxiety is influenced by the occupation and previous operation experience of the patients. Early and accurate identification of anxiety-prone people before operations will be of great significance to the use of a more optimized analgesia scheme to reduce postoperative pain. Effective postoperative analgesia is conducive to the recovery from disease. We should not neglect the management of postoperative pain because of the small trauma of laparoscopic surgery. The combination of dexmedetomidine and opioids can play an important role in analgesia and improve the quality of anesthesia.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by Ethics Committee of Shanxi Provincial People’s Hospital. The patients/participants provided their written informed consent to participate in this study.LZ and L-JH conceived the idea and conceptualized the study. X-LH collected the data. Y-LW, L-SJ, and R-NS analyzed the data. LZ drafted and reviewed the manuscript. All authors read and approved the final draft.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.