Despite its prevalence, there is no clear-cut diagnostic path or treatment paradigm for fibromyalgia; this can lead to a multiplicity of symptoms and comorbid conditions that complicate care. “Overlapping symptoms” describe conditions that can occur concomitantly with fibromyalgia and include migraine, irritable bowel syndrome, obesity, and pelvic pain syndromes. A variety of pharmacologic and nonpharmacologic treatments are available for fibromyalgia, but treatment is best personalized for an individual and recognizes potential comorbidities. Opioids are not the recommended front-line treatment, cannabinoids hold promise but with limitations and nonpharmacologic options, such as aerobic or resistance exercise and cognitive behavior therapy, can play a very important but often underestimated role. Amitriptyline appears to be safe and effective in treating six of the main fibromyalgia domains: pain, disturbed sleep, fatigue, affective symptoms, functional limitations, and impaired cognition (“fibro fog”). Very low-dose naltrexone (2.5-4.5 mg) may offer analgesic and anti-inflammatory benefits to fibromyalgia patients, but further studies are needed. Fibromyalgia can be a devastating and debilitating condition for patients, and clinicians are challenged with its diagnosis and treatment as well. Further research as well as compassionate approaches to offering personalized care to those with fibromyalgia are required. Despite its global prevalence, fibromyalgia is associated with protracted diagnostic delays, on average 2.3 years . PatientThe etiology of fibromyalgia is not elucidated, but this condition may be part of a larger metabolic deficiency in the serotoninergic system . LackingThis article is a review of materials presented at the “Past, Present and Future in Pain Medicine, Second Edition” congress held in Tunis, Tunisia, from May 11 to 13, 2023. Materials were presented by the authors based on their research and clinical experience. The aim of this review is to describe the findings of this panel of experts on fibromyalgia.Pain signaling in fibromyalgiaThe neurotransmitters associated with pain signaling include glutamate, substance P, nerve growth factor (NGF), and serotonin (5HT-2A and 5HT-3A). The neurotransmitters that inhibit the transmission of pain signals are norepinephrine-5 serotonine , dopamine, endogenous opioids, endocannabinoids, and gamma-aminobutyric acid (GABA) . A patieComorbidities and overlapping symptomsCompared to the general population, a higher proportion of fibromyalgia patients experience psychiatric and rheumatologic conditions, and these comorbidities can obscure diagnoses and complicate care . Among tIt is far more accurate to talk about “fibromyalgia syndrome” that includes so-called “overlapping symptoms” of multiple conditions. A new nosology has been proposed with the recognition of central sensitivity syndrome in fibromyalgia . This isOur understanding of these fibromyalgia comorbidities remains limited. For example, obesity has been recognized as a common fibromyalgia comorbidity that exacerbates symptoms. In a study of 215 fibromyalgia patients, obesity in fibromyalgia patients was related to higher sensitivity to pain, reduced physical strength, less sleep, and increased restlessness during sleep compared to controls . The oveAmong patients with rheumatoid arthritis, axial spondylarthritis, and psoriatic arthritis, the incidence of fibromyalgia is higher than in the general population . These cIn fibromyalgia patients, the symptoms of comorbid conditions can be more severe than symptoms that occur in isolation. For instance, patients with fibromyalgia and comorbid migraine have more intense headaches, a greater likelihood of severe headaches, and more symptoms of depression compared to those with migraine alone . About 2Since fibromyalgia patients are at an elevated risk for comorbid conditions, such as psychiatric disorders and rheumatic conditions, it is important to screen fibromyalgia patients for such conditions rather than assuming that somatic symptoms are all attributable to fibromyalgia. Identifying comorbidities can delineate effective treatment strategies, improve outcomes, and may even reduce symptoms of fibromyalgia itself .Differential diagnosis is complicated by the fact that fibromyalgia mimics the symptoms of other conditions, such as lupus, multiple sclerosis, rheumatoid arthritis, polymyalgia rheumatica, axial spondyloarthritis, thyroid disease, T2DM, anemia, and chronic fatigue syndrome . PatientThe pathway to care typically starts with a first-level clinician, such as a general practitioner, with a subsequent referral to a rheumatologist or other specialist . The maiTreating fibromyalgiaFibromyalgia is usually treated with a multipronged approach that includes patient education, nonpharmacological strategies such as exercise or cognitive behavioral therapy, and pharmacological treatments such as gabapentinoids, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, low-dose naltrexone, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and cannabinoids Table  27]. A . A 27]. Advances in fibromyalgia studies caused the European League Against Rheumatism (EULAR) to issue the 2017 recommendations that shift away from reliance on expert opinion to more evidence-based recommendations ,32. DespGabapentin and PregablinThe gabapentinoids, pregabalin and gabapentin, are anticonvulsants that act by reducing the calcium-dependent release of glutamate, norepinephrine, calcitonin gene-related peptide, and substance P. As such, they treat neuropathic pain as well but with some well-known limitations. Their analgesic benefit may be modest; also, there are potentially treatment-limiting side effects and not all patients respond to them . There iAmitriptyline and Other AntidepressantsAmitriptyline is a tricyclic antidepressant that is often recommended as monotherapy or part of a combination regimen to treat fibromyalgia pain. One of the first tricyclic antidepressants to be approved for the market, amitriptyline inhibits serotonin and norepinephrine reuptake and may be active at histaminergic, muscarinic, and norepinephrine receptors . AmitripSerotonin and norepinephrine reuptake inhibitors have been shown to be effective in decreasing pain intensity in fibromyalgia patients. Duloxetine is described as a balanced serotonin and noradrenaline reuptake inhibitor and is indicated to treat diabetic peripheral neuropathy, major depressive disorder, and urinary stress incontinence . It has Milnacipran, at doses of 100-200 mg/day, is a serotonin-norepinephrine reuptake inhibitor and is one of only a handful of agents expressly developed to treat fibromyalgia . While iThere are a few head-to-head studies on fibromyalgia agents. A meta-analysis of various fibromyalgia treatments indirectly compared pregabalin, amitriptyline, and duloxetine at various dosages and reported that amitriptyline 25 mg had superior results, followed next by pregabalin 450 mg .OpioidsA study, including 14 fibromyalgia, 10 chronic low back pain, and 6 healthy control patients who received lumbar puncture, was conducted to analyze the amount of Met-enkephalin-Arg6-Phe7 (MEAP) and nociceptin immunoreactive materials in their cerebrospinal fluid. The fibromyalgia patients had higher MEAP concentrations in their cerebrospinal fluid, more systemic symptoms, and lower pain thresholds compared to the back pain patients and the control group . Thus, eTramadol, considered a weak opioid agonist, is the exception to the rule. Tramadol has a mechanism of action related to serotonin reuptake inhibition. In a 91-day study of fibromyalgia patients taking a fixed-dose combination product of 37.5 mg tramadol and 325 mg of paracetamol (acetaminophen), the tramadol-paracetamol patients had significantly less pain and better function than control patients and no serious adverse events were reported .Low-Dose NaltrexoneAt doses of 50-100 mg, naltrexone is approved in the United States to treat opioid or alcohol use disorder and opioid dependence, but at very low doses of 2.5-4.5 mg, the agent has analgesic and anti-inflammatory properties, confirmed in a study of 31 fibromyalgia patients . In a stNonsteroidal Anti-inflammatory DrugsNSAIDs are typically not effective in treating fibromyalgia pain because they have peripheral rather than central mechanisms of action -56. SincCannabinoidsDespite legalization efforts and a wealth of new research, clinicians are still not confident about how to prescribe cannabinoids, what forms of cannabinoids and routes of administration to recommend, or how well cannabinoids will work for fibromyalgia symptoms . CannabiThe endocannabinoid system is active in both central and peripheral nervous systems and modulates pain at the spinal, supraspinal, and peripheral levels ,61. CannIt should be noted that cannabinoids are relatively contraindicated for those under the age of 21 years and in people with a history of or active substance use disorder, mental health condition, congestive heart failure or cardiovascular disease/risk factors, and in people suffering from palpitations and/or chest pain. Cannabinoids may be associated with mild to severe adverse events, such as dizziness, drowsiness, hypotension, hypoglycemia, disturbed sleep, tachycardia, cardiac palpitations, anxiety, sweating, and psychosis .When used in a balanced way, cannabinoids may rightly be considered for managing fibromyalgia symptoms despite the lack of evidence, particularly in patients suffering from chronic painful symptoms for which there is little other source of relief. When effective, cannabinoids may be opioid-sparing pain relievers.When considering cannabinoids for a fibromyalgia patient, the clinician must be open and empathetic to the patient while still being frank about potential risks and benefits. Many people regard cannabis products as essentially harmless, which is not the proper attitude for analgesic treatment . CliniciNonpharmacologic ApproachesExercise, particularly aerobic exercise and resistance training, improves function in fibromyalgia patients and can reduce pain intensity, in addition to the other well-known benefits of exercise such as improved mood, enhanced flexibility, and weight loss. The general recommendation is exercising for at least 20 minutes once a day, two or three times per week. For those who cannot exercise 20 minutes, two 10-minute exercise periods per day may be substituted, but patients should strive for 20 minutes in one day. Strength training at intensities of 40%-80% with 4-20 repetitions per exercise is recommended two to three times weekly ,69,70.Cognitive behavioral therapy (CBT) uses a paradigm whereby fibromyalgia is regarded as a biopsychosocial phenomenon in which an overactive emotional system overwhelms a less functional coping system. This so-called salience network means that the body is continuously on a high alert against threats that it cannot manage . CBT canComplementary and alternative medicine offers approaches that may be helpful for those patients interested or open to these treatments. Such treatments include yoga, T’ai Chi, Qi Gong, acupuncture, cupping, traditional Chinese medicine, mindfulness, transcranial stimulation, and others -79. TherDiscussionDespite our progress and ongoing studies, there remain a couple of unanswered questions about our approach to fibromyalgia.Who Should Care for Fibromyalgia Patients?People with fibromyalgia complain about poorly coordinated care and it is known that they can experience diagnostic and treatment delays . FibromyWhat Kinds of Combinations Are Best in Combination Therapy for Fibromyalgia?Despite limited studies in this important area, it appears that exercise is a foundational component of all combination approaches. To this, educational interventions, CBT, mindfulness exercises, and in some cases pharmacologic therapy with pregabalin and/or an antidepressant can be added -87. WhilHow Do We Best Care for Fibromyalgia Patients?The best approach is to assure the patient gets a rapid and accurate diagnosis and can move forward to treatment. It is important to be pragmatic and open with the patient and explain that the diagnosis can be difficult and, once diagnosed, there is no simple treatment for fibromyalgia. A differential diagnosis is complicated by the fact that fibromyalgia mimics the symptoms of other conditions and often occurs in a comorbid relationship with other conditions. During the diagnostic process, clinicians should be professionally empathetic to patients and careful not to dismiss their reports of symptoms, even if they seem unusual or improbable. If fibromyalgia is the appropriate diagnosis, it is imperative that the clinical team work to educate the patient on treatment options, the role of combination therapy, the importance of exercise, medications, and the nature of overlapping symptoms.Fibromyalgia can be a devastating diagnosis, often exacerbated by diagnostic delays, clinical skepticism, and a lack of first-line treatment options. Fibromyalgia often exists embedded in a web of overlapping symptoms, confounding diagnosis and treatment. Optimal treatment options seem to involve combination approaches based on a foundation of exercise, weight loss, CBT, and drug therapy. Further studies are needed to better diagnose and treat this perplexing condition that is associated with pain, functional deficits, depressed mood, and disability.


Trigeminal neuralgia (TN) is a chronic pain condition that affects the trigeminal nerve, the largest of the cranial nerves. It is characterized by severe, sudden, and recurrent facial pain, often triggered by light touch or a breeze. Treatment options for TN include medication, nerve blocks, and surgery, but radiofrequency ablation (RFA) has emerged as a promising alternative. RFA is a minimally invasive procedure that uses heat energy to destroy the small portion of the trigeminal nerve responsible for the pain. The procedure is performed under local anesthesia and can be done as an outpatient procedure. RFA has been shown to provide long-term pain relief for TN patients with a low complication rate. However, RFA is not suitable for all TN patients and may not be effective for those with multiple pain sites. Despite these limitations, RFA is a valuable option for TN patients who are not responding to other treatments. Furthermore, RFA is a good alternative for a patient unsuitable for surgery. Further research is needed to fully understand the long-term effectiveness of RFA and identify the best candidates for the procedure. Trigeminal neuralgia (TN) is defined as a chronic condition characterized by the presence of unilateral neuropathic facial pain that involves the fifth cranial nerve and might result in physical and/or psychological disability ,2. The pTN is typically characterized by the presence of sudden, sporadic, intense burning or stabbing-like unilateral facial pain in the distribution of one or more branches of the affected trigeminal nerve . The paiThe treatment of TN pain can often be achieved through the use of medications such as anti-epileptic drugs or tricyclic antidepressants ,6. NeverMethodsA series of databases were searched for relevant articles published between January 2019 and December 2022. A review of recent literature indexed in PubMed, Medline, the National Library of Medicine, and Google Scholar was conducted. Our review included 27 retrospective and prospective studies investigating the role of RFA as a treatment strategy for TN. Inclusion criteria included patients >18 years old, with evidence of TN, and receiving RFA therapy. Exclusion criteria included other forms of non-trigeminal facial pain . Prospective trials were favored over retrospective studies, and large-scale cohorts were favored over smaller case series.DiscussionAccording to the International Headache Society, trigeminal neuralgia (TN) is “a disorder characterized by recurrent unilateral brief electric shock-like pain, abrupt in onset and termination, limited to the distribution of one or more than one division of the trigeminal nerve and triggered by innocuous stimuli” . AlthougTN is classified into two types, namely, (1) classical TN, purely paroxysmal, and (2) classical TN with concomitant persistent facial pain. Pain is described as superficial, sudden, severe, sharp, lancinating, and shock-like, associated with tic-like cramps of the facial muscle. Triggered by non-noxious stimuli, pain attacks occur several times daily and may worsen over time. Reportedly, the right side of the face is more affected than the left side and has a higher incidence of involvement of the V2 division of the trigeminal nerve than V3 ,10.Effective TN treatment started 40 years ago; before that, the most effective treatment was the destruction of the affected nerve branch by the injection of caustic substances or the resection of the sensory trigeminal root behind the Gasserian ganglion . CurrentThe most invasive surgical approach in treating TN is microvascular decompression, a vascular compression on the trigeminal root as the cause of TN because it removes the suspected nerve compression by the artery or vein . AnotherRFA is the most effective minimally invasive technique for treating TN. It has been recognized for its safety, efficacy, success rate, and patient satisfaction compared to balloon and microvascular decompression ,11. TherRFA may be applied in two ways at the Gasserian ganglion level, namely, thermal radiofrequency or CRF and PRF. The main difference between the two is that thermal RF causes structural damage, whereas PRF does not cause structural damage but can cause microscopic damage to the microfilaments of C-fibers . Both inNewer studies have tried to implement CT guidance instead of fluoroscopy to increase the precision of the procedure. CT guidance was used in these clinical trials as a part of a new approach focusing on targeting the peripheral trigeminal branches instead of the Gasserian ganglion itself -18. HoweAs the probe temperature during intervention is set between 60°C and 80°C, CRF by high-frequency alternating currents can lead to coagulative tissue necrosis, neuronal injury, and a higher risk of complications. On the other hand, PRF uses short high-voltage bursts, followed by a silent phase, allowing heat elimination. Reduced exposure to heat may decrease the complications, but it will also restrict the effectiveness of therapy. Some studies mentioned that combined CRF and PRF show better results ,15. RegaRF temperature is an additional factor that affects the effect of RFA. However, no current standard exists for understanding the accurate CRF temperature required for TN. According to the systematic review, few studies reported that 68°C was the optimal RF temperature for treating the maxillary (V2) and mandibular (V3) division of idiopathic TN and bilateral idiopathic TN. Others mentioned 70°C was the optimal temperature. Patient satisfaction was improved when the temperature range was 68‑70°C, and efficiency was improved at a temperature range of 66-80°C. In other studies, using temperatures of 60-65°C for V1, 72°C for V2, and 75°C for V2/V3 TN resulted in significant patient satisfaction. For PRF, a temperature range of 45-50°C has been recommended for elderly patients. The percentages of patients with initial pain relief were 77.8% to 100%. Pain recurrence was observed in 8-40 months on average .In another study, Wassim et al. treated patients with three lesions at 70° for 60 seconds each for up to three months and reported a 67% rate of recurrence-free interval after the first three months. This rate significantly increased over the years. After one year, 85.3% of patients were symptom-free, 74.6% were symptom-free at three years, and 68.0% at five years, translating to approximately 32% recurrence of symptoms at the end of five years . One stuDespite its effectiveness, RF is not free from complications, including hypoesthesia, masticatory muscle weakness, visual disturbance, keratitis, dysacusis, temporal muscle atrophy, and facial hematoma . In all On the other hand, more severe complications such as masticatory muscle weakness, facial hematoma, and corneal reflex weakness are not uncommon. Gunduz et al. have reported that out of 209 patients treated with RF, 19 patients experienced intrabuccal hematoma (9.1%), five patients had masseter muscle weakness (2.39%), and seven patients had either corneal hypoesthesia or weakened corneal reflex (3.35%) . In oldeOur review concluded that multiple factors might affect the severity of RF complications. For example, Wu et al. focused on the effect of procedure technique on these complications. On comparing PRF vs. CRF, they found that CRF was associated with a higher rate of complications  . In anotMany of our research studies introduced different approaches to mitigate the potential complications. Huang et al., Zeng et al., and Ran et al. studied the effects of applying the thermal waves extracranially at the affected trigeminal branches  instead of Gasserian ganglion to decrease the risk of intracranial infection or hemorrhage associated with penetrating the cranium -18. ZengAlthough RFA is a minor procedure, some contraindications should be carefully examined. Anesthesia was a determinant factor in a few studies, as patients were excluded if they could not medically tolerate the anesthesia. However, most studies used deep sedation only. Many studies did not include patients to avoid the risk of bleeding and hematoma. Especially in GRF procedures, patients are at a greater risk of sepsis and intracranial infections if they have local facial infections. The most common contraindication to this procedure is a mental or behavioral disease in which patients cannot express subjective feelings because the central part of the procedure is the placement of the needles, which is confirmed by nerve stimulation confirmed by the patient .Although RFA has shown to be an effective treatment for TN, it does have certain limitations. One of the main limitations of RFA is that it is not a cure for TN or other types of chronic pain. RFA can provide significant pain relief but does not address the underlying cause and is not a permanent solution. Sometimes, the pain may return after the procedure, requiring repeat treatments or alternative therapies . AnotherAdditionally, RFA is not recommended for patients with certain medical conditions, such as bleeding disorders or certain tumors . RFA alsRFA is a promising treatment option for patients with TN, providing significant pain relief and improved quality of life. Further studies are needed to compare the long-term outcomes of RFA with other treatments and determine the optimal patient selection criteria. However, it is a safe and effective alternative to other surgical procedures and should be considered a treatment option for patients with TN.


Pulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients’ daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program.Patients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables.A total of 16 patients underwent different type of resection. The majority were male  with a mean age of 44 years (19–81). Most common clinical stage was stage I  with typical carcinoid features recorded in more than half of the cases . Almost all patients underwent surgical excision  with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure  and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients  were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10.Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients’ lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented. Pulmonary carcinoids account for 27% of carcinoid tumors and less than 1% of all lung cancers . HoweverThe anatomical location of these carcinoid tumors within the bronchus and bronchioles poses a threat to the surrounding parenchyma. The majority of bronchial carcinoids are malignant and capable of metastasizing. This is more distinctive of atypical carcinoids which display aggressive behavior and spread both locally and distally. Therefore, surgical resection might lead to shortness of breath and exercise induced fatigue knowing that the decrease in lung function is clinically irrelevant. Additionally, resection may impact patients’ ability to undertake daily activities due to decreased lung reserve and postoperative pain. Morality with pulmonary carcinoid following resection is around 4.1% with a high overall 15-year survival of 77.5% , 7. ThesThe aim of this study is to analyze postoperative quality of life, pain and pulmonary function of patients at our institution when a good peri-operative pulmonary and physical rehabilitation programs as well as pain management service were adopted and strictly implemented on these surgical patients. To our knowledge, no study to date specified the quality-of-life evaluation for lung carcinoid patients following surgical resection with extensive pain score evaluation.From a prospectively maintained electronic health record registry, data encompassing demographics, tumor characteristics and treatment outcomes was gathered for patients who underwent surgical treatment for localized pulmonary carcinoid tumors between (August 2017- March 2020) at the King Hussein Cancer Center (KHCC). The study was approved by the institutional review board (IRB) with the number 19KHCC146. Data of tumor characteristics included histological subtype, mitotic rate (per high power field), Ki67, staging, lymphovascular invasion, largest tumor diameter (cm) and the presence of positive lymph nodes. All patients underwent primary curative surgical resection without neoadjuvant chemoradiotherapy. None of the patients were diagnosed with carcinoid syndrome. Oral consent to conduct the quality of life and pain questionnaires was obtained through an IRB approved phone script.We designed the perioperative pulmonary care bundle on multiple stages starting at the time of diagnosis. If a patient was an active smoker, cessation guidance and counseling was provided. On admission, the patient was educated and trained by a respiratory therapist about aspiration prevention, deep breathing exercises, incentive spirometer use, and chest physiotherapy. Minimally invasive approach was utilized when feasible. Early post-operative mobilization was accompanied by adequate pain control achieved by specialized pain team .A pulmonary function test (PFT) was conducted pre-operatively and repeated after surgery to document a change in lung capacity and ventilation using values of Forced Expiratory Volume (FEV1) and diffusing capacity of the lungs for carbon monoxide (DLCO). Post-operative PFT was performed at an average of 2 years.After obtaining an oral consent, the Arabic version Activity of Daily Living (ADL) instrument  was condThe Arabic version of Short-form McGill Pain Questionnaire (SF-MPQ) by Terkawi et al.  was perfAll statistical analysis has been conducted on SPSS version 24. The findings of the study have been presented as descriptive statistics. The relationship between categorical data has been tested using the Chi-square test, while continuous data associations were evaluated using ANOVA. A value of ≤ 0.05 (CI = 95%) is considered statistically significant.Our study included 16 patients with the majority being male  and a mean age of 44 years (± 19.53). Patients stratified according to stage as: stage I  and stage II . Histopathological features showed typical carcinoid in 11 patients (69%) and atypical histology in 5 patients (31%). Only one patient (6%) received adjuvant chemotherapy. Two patients (13%) were found to have positive lymph nodes, each one of them with only one hilar lymph node involved. No major postoperative morbidity or mortality was observed. Pain management is maintained by shoulder block, intercostal block, and paravertebral block intra-operatively, followed by close observation by the pain team who administer patient controlled analgesia then transition into oral pain medication. All patients were alive when contacted with no local or distant tumor recurrence (Table Fifteen of the patients (94%) underwent complete tumor resection which included: parenchymal preserving, wedge resection, lobectomy, bilobectomy, sleeve lobectomies and pneumonectomy. Bi-lobectomies were performed on tumors located at the bifurcation of middle and lower lobe bronchi with an average size of 2.3 cm. A single patient required endobronchial debulking is an 82-year-old with multiple comorbidities who cannot tolerate lung resection. Complete microscopic resection with negative margin was achieved in all cases. The use of minimally invasive video-assisted thoracic surgery (VATS) was reserved for 8 patients (50%) who were deemed eligible Fig. .The collective mean preoperative DLCO was 105.07 as compared to 95.92 postoperatively (p = 0.437). In terms of FEV1, the mean preoperative value was 88.00 ± 20.785 and became 75.75 ± 19.82 postoperatively (p = 0.133). Changes in FEV1 and DLCO were not statistically significant  scored an average intensity of 1.625 out of 10. The mean sensory pain was 0.085 out of 3 and affective pain was 0.078. The most common type of pain described by patients was cramping in 4 patients scored as mild to moderate. This was followed by moderate to severe throbbing mean in 3 patients  were totally independent and only one patient (6%), who had undergone endobronchial debulking due to his multiple comorbidities, was partially dependent.Based on our data, carcinoid tumor resection modality does not seem to have an effect on pulmonary function test if patients were conditioned properly in the peri-operative period. All of our patients, with exception to one were found to have that surgery had no effect on their daily activities and function. Those who reported minimal pain after surgery, did not require any form of analgesia and were able to function normally.An interest in patient-centered outcomes is witnessing an escalation in healthcare management. It is pivoted on long-term outcomes like health-related quality of life, residual dysfunctions, and chronic pain rather than focusing on endpoints such as morbidity and mortality. Hence, we call for informing patients about the effect of lung resection on postoperative residual function and quality of life (QoL).A number of studies investigate risk factors leading to a decline in postoperative QoL after lung resection, predicting and evaluating models to predict postoperative QoL , 12. AdvWith adequate peri-operative pain control, chronic post-operative pain can be avoided. Chronic post-surgical pain (CPSP) is defined as persistent pain three months after thoracic surgery, different in nature from preoperative pain, and is not caused by other conditions . The majVariability exists in the radicality of surgical approaches for resection of bronchopulmonary carcinoids. Current options including parenchymal preserving; where the bronchus is resected and anastomosed while the lung remain intact, wedge resection, lobectomy including sleeve lobectomy, bilobectomy and pneumonectomy. When tumors are located at the bifurcation of lobe bronchi, a sleeve resection to preserve any of the lobes is necessary. The effect of pulmonary resection on lung function is attributed to the magnitude, site and modality utilized for resection. Moreover, postoperative pulmonary rehabilitation and the prevention of lung fibrosis influence the extent of diminished lung function. Keenan et al. found that less radical resection of pulmonary tumors offers preservation of lung function compared to a more aggressive approach . SimilarFollowing surgery to remove pulmonary carcinoid tumors, long-term outcomes including higher survival rates, controlled symptomatology, and decreased likelihood of tumor recurrence may be achieved. Our data reported a minimal effect of extensive lung resection on postoperative lung function, quality of life and pain when we adopt a good peri-operative pulmonary and physical rehabilitation programs as well as pain management service. Despite the limited number of patients analyzed, we believe our findings support the use of aggressive surgical resection for this rare entity.


PurposeThe objective of this study was to investigate whether cryotherapy is effective in reducing pain, opioid consumption, and length of stay (LOS) in hospital following total knee arthroplasty (TKA).MethodsThis prospective cohort study included 191 consecutive patients who underwent TKA without having access to cryotherapy, followed by 193 consecutive patients who underwent TKA and received automated cryotherapy as part of the recovery phase. All patients had their surgical procedures performed by the same surgeons and received post-operative care by the same nursing, medical, and physiotherapy team. The pain score using the visual analog scale (VAS)and the amount of opioid used on the first three post-operative days were recorded along with the length of hospital stay.ResultsThere was no difference in baseline characteristics between the two groups. The use of cryotherapy was associated with a reduced pain score on all three days compared to when cryotherapy was not used: Day 1 pain score was 5.2 versus 6.1 (p < 0.01), Day 2 was 3.6 versus 4.8 (p = 0.03), and Day 3 was 2.8 versus 3.8 (p < 0.01). Cryotherapy was also associated with a significant reduction in analgesia consumption on all three days. The median amount of Oramorph used on all three days in the cryotherapy group was 15.0 mg compared to 40.0 mg in the control arm (p < 0.01). Additionally, the LOS was shorter in the cryotherapy group, with a mean of 3.86 days versus 4.20 days in the control group (p = 0.02).ConclusionThe use of cryotherapy following TKA was associated with decreased pain and opioid consumption along with a reduced time to hospital discharge compared to when no cryotherapy was used. Total knee arthroplasty (TKA) is a well-established procedure for managing end-stage osteoarthritis, providing significant relief from pain and improved joint function . Over 80Patient selectionThis prospective cohort study was conducted at an elective orthopedic teaching hospital between March 2022 and February 2023. The hospital review board reviewed the study and advised that further assessment by the institutional board for ethical approval was not required. Patients aged 18 to 80 years undergoing primary, unilateral TKA were invited to participate in the study, and written consent was obtained. The exclusion criteria included patients undergoing unicompartmental, bilateral, or revision knee arthroplasties. Of the 457 patients identified, 400 met the inclusion criteria. The use of automated cryotherapy at our hospital was introduced in September 2022. Patients undergoing TKA from March to August 2022 were assigned to the control group, while those operated on from September 2022 to February 2023 were assigned to the intervention arm, receiving cryotherapy routinely post-operatively. An additional seven and nine patients were excluded from the cryotherapy and control groups due to poor compliance in filling out pain questionnaires. In total, data from 193 patients in the cryotherapy group and 191 patients in the control group were analyzed. Figure Surgical techniqueAll patients received a primary unilateral TKA by experienced surgeons under general anaesthesia. At induction, they received 1g of tranexamic acid along with 1.5 g of cefuroxime as surgical prophylaxis. As per the surgeons’ approach, a pneumatic tourniquet was applied but not inflated unless they had trouble in achieving hemostasis. All knees were approached using a midline anterior incision with a medial parapatellar approach. The implant system used was the Stryker Triathlon Total Knee System®, which uses both cruciate-retaining (CR) and posterior-stabilized (PS) implants. Before skin closure, hemostasis was controlled using diathermy, and no wound drainage was used post-operatively. Patients received a further 500 mg of tranexamic acid six hours post-operatively, along with two further 750 mg doses of cefuroxime eight hours apart. Post-surgery, patients were also provided with two weeks of venous thromboembolism prophylaxis and were encouraged to commence early full weight-bearing activities under the guidance of a physiotherapist starting from the first day.InterventionFollowing TKA, patients in the intervention arm started receiving cryotherapy through an automated device. The device used was the Zamar Therapy Cube®, which allows a fixed temperature to be reached. The devices were set at 10 degrees Celsius, and patients started receiving cryotherapy within one hour of returning to the ward. The nursing staff applied the cryotherapy cuffs, and participants received four sessions daily, each lasting up to two hours. Participants in the control arm did not receive cryotherapy or any cold treatment.Post-operative inpatient careFollowing their return from the recovery unit, all patients were prescribed regular analgesia per the WHO analgesic ladder . They reData collectionData collected included patient demographics such as gender, age, and ethnicity. Information such as BMI, American Society of Anaesthesiologists (ASA) grade , and preStatistical analysisA sample size calculation was performed to recruit enough patients to detect a minimum pain score improvement of 25%. This proportion was agreed upon by consensus among the authors as significant enough to impact the population and warrant implementation in hospitals. With a 95% confidence interval and a margin of error of 0.05, a sample size of at least 289 patients was required. Following the recommendations of the senior author , this number was increased to 400 patients to account for potential non-compliance, technical issues with the cryotherapy devices, or patients rescinding their consent later.When comparing baseline characteristics and outcome measures between the two groups, an unpaired t-test was used for data that followed a normal distribution. For data not normally distributed, the Wilcoxon-Mann-Whitney test was used to determine the significance of differences between the two groups. Continuous variables that were normally distributed were expressed as mean and SD, whereas those not normally distributed were displayed as median and interquartile range (IQR). Categorical variables were presented as the number and percentage of patients. A p-value of less than 0.05 was considered statistically significant, and statistical analysis was performed using IBM® SPSS® Statistics software version 21.0 .There was no statistical difference in baseline characteristics between patients receiving cryotherapy and those in the control group, implying that both groups' populations were homogeneous Table . The stuPatients receiving cryotherapy also used significantly less Oramorph compared to those in the control arm, and again, the difference was statistically significant on all three days (Mann-Whitney U test). Figure The use of cryotherapy was associated with reduced LOS following TKA. The mean LOS was 3.86 days in patients receiving cryotherapy compared to 4.20 days for those in the control group. This difference of 0.34 days was statistically significant (p=0.02). Figure In this prospective cohort study, the baseline characteristics between patients in both groups were the same. The same surgeons performed patient operations and received peri-operative care from the same anesthetic team. During the post-operative recovery phase, the same team of nurses, medical doctors, and physiotherapists were involved in their care. The use of cryotherapy was associated with reduced post-operative pain, decreased analgesic requirements, and a decreased LOS compared to when cryotherapy was not used. Our findings suggest that implementing cryotherapy as part of the post-operative recovery phase would promote early functional recovery and reduce time spent in the hospital following TKA.When analyzing data from the National Joint Registry of England and Wales, pain following TKA was found to be the strongest predictor of patient dissatisfaction and reduced functional outcome, including the Oxford Knee Score . RegressThe use of high amounts of opiate following TKA is thought to have a negative influence on post-operative rehabilitation. This is due to side effects such as nausea and dizziness, which may prolong a hospital stay and contribute to poor patient experience ,17. Our When interpreting the results of our study, several limitations need to be considered. Firstly, this study did not evaluate long-term clinical outcomes. We only looked at pain score and analgesic usage within the first three post-operative days when it was assumed the pain would be at its highest. Nor did we follow-up patients on their discharge to assess for any post-operative complications that might develop in the community. Secondly, patients and observers reporting outcomes of interest could not be blinded as data was collected prospectively when patients had the cryotherapy device on. Thirdly, we did not consider the pre-operative grading of arthritis and radiological outcomes when assessing baseline characteristics of patients. This has the potential to influence a patient's tolerance of pain and thus have a direct effect on the outcomes measured.Despite the limitations, this study remains the largest one to date, assessing the effects of cryotherapy on pain, analgesic usage, and time to discharge. Cryotherapy was associated with reduced post-operative pain, decreased analgesia requirements, and a reduced LOS. Given the findings of our study, we would encourage the use of cryotherapy as part of standard recovery following TKA.The use of cryotherapy following TKA is associated with reduced post-operative pain, reduced analgesia usage, and early functional recovery. Establishing its usage should be incorporated in post-operative recovery following knee arthroplasty.


Neuropathic pain after spinal cord injury (SCI), both traumatic and non-traumatic, is refractory to various treatments. Spinal cord stimulation (SCS) is one of the neuromodulation therapies for neuropathic pain, although SCS has insufficient efficacy for neuropathic pain after SCI. The reasons are presumed to be inappropriate locations of SCS leads and conventional tonic stimulation itself does not have a sufficient analgesic effect for the pain. In patients with past spinal surgical histories, the cylinder-type leads are likely to be placed on the caudal side of the SCI because of surgical adhesions. Differential target multiplexed (DTM) stimulation is one of the latest new stimulation patterns that is superior to conventional stimulation.A single-center, open-label, randomized, two-way crossover trial is planned to investigate the efficacy of SCS using DTM stimulation placing a paddle lead at the appropriate site for neuropathic pain after SCI in patients with spinal surgical histories. The paddle-type lead delivers energy more efficiently than a cylinder-type lead. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). The primary outcome is rates of achieving pain improvement with more than 33% reduction 3 months after SCS system implantation. The secondary outcomes are to be evaluated as follows: (1) effectiveness of DTM and tonic stimulations during the SCS trial; (2) changes of assessment items from 1 to 24 months; (3) relationships between the result of the SCS trial and the effects 3 months after SCS system implantation; (4) preoperative factors associated with a long-term effect, defined as continuing for more than 12 months; and (5) whether gait function improves from 1 to 24 months.A paddle-type lead placed on the rostral side of SCI and using DTM stimulation may provide significant pain relief for patients with intractable neuropathic pain after SCI in patients with past spinal surgical histories.Japan Registry of Clinical Trials (jRCT) jRCT 1042220093. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is approved as a member of the Primary Registry Network of WHO ICTRP. Spinal cord injury (SCI) induces paralysis and other dysfunctions, typically pain symptoms, in 30–80% of SCI patients –4. Pain Spinal cord stimulation (SCS) is one of the neuromodulation therapies, and it has been used for decades to treat chronic neuropathic pain , 16. TheIn patients with past spinal surgical histories, the cylinder-type leads are likely to be placed on the caudal side of the SCI because of adhesions around previous surgeries. The pain relief mechanism of SCS is based on the gate control theory , 25. AccRecently, several new stimulation patterns without paresthesia have been developed –32. DiffWe hypothesized that DTM stimulation using a paddle-type lead placed on the rostral side of the SCI provides sufficient pain relief for patients with intractable neuropathic pain after SCI with past spinal surgical histories. In fact, we have reported three cases of good outcomes using this method . The aimThis is a prospective, single-center, open-label, randomized, two-way crossover, exploratory trial.Patients are selected based on the inclusion and exclusion criteria described below. The main criterion for enrollment is intractable neuropathic pain after traumatic or non-traumatic SCI with histories of spinal surgery at the site where the SCS lead will pass or be placed. Patients will be recruited from new patient from standard clinical practice at Nagoya University Hospital.▪ Patients with intractable neuropathic pain after SCI resistance to drug treatments▪ Patients with histories of spinal surgery at the site where the SCS lead will pass or be placed▪ 18 years of age or older▪ Visual analog scale (VAS) score for pain greater than 40 points▪ Patients classified as Frankel grade B–E▪ Patients in whom a paddle-shaped lead can be placed on the rostral side of the spinal cord lesion▪ Patients who have given written, informed consent.▪ Patients for whom local and general anesthesia cannot be performed▪ Patients classified as Frankel grade A▪ Patients receiving anti-cancer therapy▪ Patients with a history of drug abuse▪ Patients at high risk for surgery, such as patients with unstable angina pectoris and with end-stage liver disease presenting with hepatic encephalopathy▪ Patients with diabetes mellitus who are not well controlled (HbA1c ≥9%)▪ Patients with serious complications ▪ Pregnant or potentially pregnant patients▪ Patients considered inappropriate by a head of research or investigatorPotential participants will be identified from patients who visit Nagoya University Hospital. After assessment by clinical research physicians regarding inclusion and exclusion criteria, the study information will be given to potential participants. Written and verbal informed consent will be obtained. The right of a participant to refuse to participate in this trial without giving reasons for the decision will be respected. This trial does not involve collecting biological specimens for storage.This trial consists of a two-step procedure. The first step is an SCS trial, and the second step is SCS system implantation. The lead locations for the SCS trial and SCS system implantation are the sides caudal and rostral to the SCI, respectively. In the SCS trial, two cylinder-type leads  are to be inserted on the caudal side of the SCI under local anesthesia, so that the lead does not pass through the SCI. Once inserted, the two leads are directly sutured to the skin at the puncture sites without skin incision. The order of stimulation patterns of DTM or tonic is randomly assigned to two courses evenly  and pulse width (40–300 µs) are set by clinical research physicians so that the patient feels comfortable with paresthesia. The voltage is adjusted by the patient using a remote controller to the intensity level of eliciting comfortable paresthesia for 2 days.DTM stimulation delivers multiple electrical signals and stimulates multiple locations without paresthesia. DTM stimulation consists of one stimulation signal on the upper side of the lead, called the base program, and multiple stimulation signals on the lower side of the lead, called the prime program. For the base program, frequency (50 Hz), pulse width (200 µs), and voltage (approximately 70% of the paresthesia threshold) are set. For the prime program, frequency (300 Hz), pulse width (170 µs), and voltage (approximately 65% of the paresthesia threshold) are set. DTM stimulation delivers electrical signals from one base and three prime programs. DTM stimulation is set by clinical research physicians; the stimulation continues for 2 days, and the patient does not adjust the stimulation parameters.Any patients requesting to end their participation in the study can be withdrawn from the study regardless of the stage they have reached in the study process. Patients do not have to provide the reason of withdrawal. Patients found to be pregnant or those judged ineligible to continue participating in the study by the investigators will also be withdrawn from the study.All treatments will be administered to participants during their stay in the hospital by attending surgeons. Therefore participants’ adherence to interventions is assured.All other treatments will be allowed.All patients who will suffer harm from trial participation will be covered by the Japanese public healthcare system.At entry, clinical research physicians obtain information from patients regarding age, sex, past history, medications, cause of SCI (traumatic or non-traumatic), level of SCI , location of pain , degree of paralysis , sensory disturbance , duration of disease, and Frankel grade (B-E). During the SCS trial, the degree of pain is evaluated using a VAS according to the plan Table . After S®). Assessment of gait function is performed by functional ambulation category (FAC).Assessments of pain relief are performed by a VAS and the short-form McGill pain questionnaire-2 (SF-MPQ-2). Assessments of mental health and comprehensive health are performed by the pain catastrophizing scale (PCS), quick inventory of depressive symptomatology (QIDS-J), and the Short-Form 36-item health survey  taken before the initial spinal surgery for SCI. Before the SCS trial, whole spinal MRI is performed to rule out any other abnormal findings, and whole spinal X-rays are also performed to confirm the location and type of fixation devices implanted in previous spinal surgeries. After the SCS trial and SCS system implantation, spinal X-rays and computed tomography (CT) are performed to confirm the location of the SCS leads and to rule out postoperative complications.Pain improvement is defined as more than a 33% reduction in the VAS score. The primary outcome is rates of achieving pain improvement at 3 months after SCS system implantation.®, at 1, 3, 6, 12, 18, and 24 months from SCS system implantation; (3) relationship between the result of the SCS trial and the effect 3 months after SCS system implantation; (4) evaluation of preoperative factors associated with a long-term effect, defined as continuing for more than 12 months; (5) evaluation whether there is improvement of motor function using the gait function scale (FAC) at 1, 3, 6, 12, 18, and 24 months from SCS system implantation; and (6) adverse events related to this study 3 months after SCS system implantation.The secondary outcomes are as follows: (1) evaluation of effectiveness of DTM and tonic stimulations in the SCS trial; (2) evaluation of changes of assessment scores, VAS, SF-MPQ-2, PCS, QIDS-J, and SF-36There is no reference clinical data for the efficacy of DTM stimulation using a paddle-type lead placed on the rostral side of the SCI because there is only one case report . TherefoRegistration, randomization, and data collection are performed using an electronic data capture (EDC) system. Randomization is performed centrally through the web-based system with a minimization procedure. The allocation sequence using the web-based system is generated by YK and MA belonging to the Department of Advanced Medicine of Nagoya University Hospital. Enrolling participants and assignment to interventions are performed by TT. Data will be collected via research electronic data capture (REDCap). Statistical analyses are planned at the data center .The results of the allocation will be shown via the interactive web response system.Trial participants will be blinded to which group they are assigned.Not applicable. The study design is open label with only data analysts being blinded so unblinding will not occur.Medical interviews and adjustments of SCS will be booked for all patients.The form used to code patients will be stored in a locked cabinet with logged access only available to the researchers and administrators responsible for the study.Not applicable.A logistic regression analysis using stimulation timing , stimulation pattern , pre-VAS values for each stimulation, and interaction between stimulation timing and stimulation pattern as explanatory variables. The carryover effect is examined by testing the interaction term at a significance level of 10%. If a carryover effect is observed, an additional analysis will be performed using only Stim-1.®) are calculated for each evaluation time point including pre-implantation and post 1, 3, 6, 12, 18, and 24 months using linear mixed models with time points as fixed effects. The amount of change of each item at each time point is compared after using the Dunnet-Hsu correction for multiple comparisons.Adjusted means and 95% confidence intervals (CIs) of the rate of change or amount of change for each item  and the effectiveness for 33% improvement on the VAS at 3 months after implantation.Preoperative factors associated with long-term effects are examined using logistic regression analysis as explanatory variables for the following items: sex, age (<60 years vs. ≥60 years), disease duration, pain site , level of SCI , paralysis , sensory disturbance , and Frankel classification .Probability of gait improvement is estimated, defining an improvement as 1 point or more in the FAC category. The probability of improved cases and the 95% CIs will be calculated at each evaluation time point.The primary outcome will be estimated as the probability of patients achieving more than 33% pain improvement on the VAS at 3 months after SCS system implantation. The secondary outcome analyses are as follows:Safety analysis will be performed by tabulating the number and probability of each event.Interim analyses are not planned.No statistical methods will be used to compensate for missing data.Details of the full protocol, participant-level data, or statistical code will not be publicly available. Unpublished data will be made available upon reasonable request to the corresponding author of the publication.Nagoya University will serve as the coordinating center. Only the investigators and members of the data center will have access to the anonymized data in REDCap.Two participating researchers at Nagoya University Hospital will monitor the data. They have the responsibility of verifying patients’ eligibility, written informed consent, compliance with the protocol, and accuracy of the data in REDCap.Researchers will immediately report serious adverse events associated with the trial to the chief investigator. Then, the chief investigator will report serious adverse events to the director of the hospital and the principal investigator. Data about all serious adverse events will also be collected in REDCap.During the study period, monitoring will be carried out by the monitoring staffs to ensure that the study is conducted properly. Monitoring staffs are SM and YN, and they are member of the trial team. The monitoring will be conducted by visits, e-mail, etc. at an appropriate frequency. Check the following items: (1) consent acquisition, (2) conducted eligibility, (3) observance of the study protocol, (4) presence or absence of diseases, (5) consistency between source documents and case reports, (6) confirmation of serious illness, (7) clinical study procedures, and (8) storage status of documents.Any protocol modifications will be reviewed by the Certified Review Board of Nagoya University Graduate School of Medicine and then registered at jRCT. All relevant information will be shared among the researchers.The results of this study will be published in a peer-reviewed journal and presented at national and international medical congresses.In general SCS procedures, the SCS lead is placed at the same position in the SCS trial and in SCS system implantation. The appropriate SCS lead position for achieving pain relief is the rostral side of the SCI. However, in patients with past spinal surgical histories, adhesions around past spinal surgeries make it difficult to pass the cylinder-type leads through the SCI site. On the other hand, paddle-type lead placement is more invasive than insertion of cylinder-type leads because it requires laminectomy under general anesthesia. Therefore, an SCS trial using a paddle-type lead is not reasonable. In this study protocol, the SCS trial is planned using cylinder-type leads placed on the caudal side of the SCI. The SCS lead positions are not theoretically appropriate on that side and may not show sufficient pain relief effects. The reasons for performing this SCS trial are as follows. The first reason is to avoid the risk of bleeding or tissue damage by passing the cylinder-type leads through the SCI site. The second reason is to assess whether the result of the SCS trial with caudal stimulation of the SCI is a predictor of the long-term effects of SCS implantation with rostral stimulation of the SCI. The last reason is to provide patients time to decide on permanent SCS system implantation.The cutoff line for determining whether a treatment is a success or not is important. The 30% to 40% range in pain reduction is widely used as a standard for clinically significant improvement. Hanley et al analyzed the relationship of pain intensity and meaningful change in pain for chronic pain after SCI and amputations . They coThis manuscript is based on the protocol . The first patient will be recruited in 2023. Recruitment will be completed by March 2028


Temporomandibular joint disorders (TMDs) represent a group of conditions that cause pain and dysfunction in the joints and muscles responsible for jaw movement . These dThe societal implications of TMDs are substantial and often underestimated. The National Institute of Dental and Craniofacial Research estimates that over 10 million Americans are affected by TMDs . The disOn an individual level, TMDs are associated with reduced quality of life. The symptoms—persistent pain in the jaw, headaches, and difficulty eating and speaking—are distressing enough to dampen the spirits of even the most resilient patients . MoreoveIn light of these significant challenges, it is paramount to adopt a treatment approach that is effective and cost-efficient and poses minimal risk to patients. While surgical approaches are hindered by certain complications ,9,10,11,The conservative and non-invasive approach to TMD treatment is generally characterized by its emphasis on risk minimization and patient education. Rather than opting immediately for invasive procedures, the first line of therapy focuses on empowering patients by providing knowledge about their condition and equipping them with tools to effectively manage their symptoms .At the heart of this approach are physical and behavioral therapies. Physical therapy exercises can enhance jaw mobility, strengthen jaw muscles, and alleviate pain, while behavioral therapies are designed to help patients cope with their pain and may reduce stress, which is known to exacerbate TMDs ,15.Pharmacological treatments can also play a role in this conservative approach, as long as they are used judiciously. Non-steroidal anti-inflammatory drugs (NSAIDs) or muscle relaxants are often recommended to alleviate pain and muscle tension in the short term. However, these are not generally considered a long-term solution due to their potential side effects, and are best used as part of a broader, multifaceted treatment plan ,17.Dental appliances, such as occlusal splints or bite guards, are another key component of the conservative treatment arsenal. These devices can help protect the teeth from grinding or clenching—common habits amongst TMD patients—and can contribute to reducing muscle tension and pain ,19.Importantly, conservative treatments underscore the importance of counseling, self-care practices, and lifestyle modifications, which can have a considerable impact on TMD symptom management. Encouraging patients to adopt healthy habits, such as maintaining a soft food diet, practicing good posture, and avoiding extreme jaw movements, can play a critical role in managing and possibly preventing the progression of TMDs ,21,22. OThis Special Issue presents a comprehensive summary of all these research areas. De Almeida et al.  comparedThis Special Issue also includes four literature reviews. The review by Pihut and Kulesa-Mrowiecka  highlighWith its broad array of high-quality research and multidisciplinary perspectives, this Special Issue on the conservative treatment of temporomandibular disorders represents a critical and enlightening contribution to this important research field.


Most patients with lumbar spinal stenosis improve significantly within 6 months of lumbar decompression surgery, however, unfavorable long-term disability may persist in some patients. It was unclear which potential influencing factors were more likely to be associated with disability. This study aimed to assess the association between disability and physical performance, pain, and pain-related anxiety in patients after lumbar decompression surgery.Patients who underwent decompression for lumbar spinal stenosis were included. Participants completed the visual analog scale, Oswestry Disability Index, and Pain Anxiety Symptoms Scale-20 to collect pain intensity, disability, and pain-related anxiety information. For physical performance assessment, participants performed timed up and go (TUG), functional reach test (FRT), 6-min walking test, and modified Sorensen test, 6–12 months after lumbar decompression surgery. The associations were examined with bivariate and multivariable linear regression analyses.r = − 0.75) and multivariable  analyses confirmed that pain-related anxiety was the strongest indicator of disability. The association between disability and pain intensity, TUG, and 6-min walking test scores was not confirmed.A total of 80 patients were included. A significant association between disability and pain-related anxiety, the FRT, and the modified Sorensen test scores was confirmed in multivariable analyses. Both bivariate (Pain-related anxiety should be considered in the rehabilitation programs after lumbar decompression surgery. The evaluation of all aspects of physical performance following lumbar decompression surgery is also recommended. Lumbar spinal stenosis is a common source of low back pain (LBP). It refers to a central canal narrowing or foraminal stenosis leading to leg and back pain. If conservative management of lumbar spinal stenosis is unsuccessful, surgical decompression surgery may be advocated to relieve symptoms . AlthougLumbar spinal stenosis is an important cause of disability . DisabilPhysical performance tests are used to assess the functional capacity of people with chronic pain and in particular LBP . The objIt is unclear which of the potentially influencing factors  could be a stronger indicator of disability in patients after lumbar decompression surgery. Understanding the association of disability with physical performance, pain, and pain-related anxiety, can be helpful in the development of interventions aimed at modifying these determinants in patients after lumbar decompression surgery.The purpose of this study was to evaluate the association between disability and physical performance, pain, and pain-related anxiety in patients after lumbar decompression surgery.An observational cross-sectional study was performed from September 2021 to September 2022 in Tehran, Iran. The study was approved by the Ethics Committee of Iran University of Medical Sciences (IR.IUMS.REC.1398.806). All participants signed informed consent before enrollment in the study.Participants were recruited via convenience sampling from one university hospital in Tehran, Iran. Adult patients that underwent lumbar decompression surgery without fusion for spinal stenosis by a single surgeon, were included. Evaluation of disability, pain intensity, pain-related anxiety, and physical performance was performed 6–12 months following surgical treatment.The inclusion criteria were: adults aged 18–60 years, receiving primary lumbar decompression surgery without fusion, and being able to actively participate in the program. Exclusion criteria were: history of prior thoracic, lumbar, or lower extremity surgery, a body mass index (BMI) greater than 35, other neurological diseases, Cobb angle of > 30, pregnancy, decompression for trauma or malignancy, and more than 2-level operation.Functional mobility was assessed using the TUG test. TUG has demonstrated acceptable reliability and validity in subjects after surgery for lumbar degenerative diseases . To perfFunctional exercise capacity was measured using the 6MWT. 6MWT is a reliable and valid tool for the assessment of functional exercise capacity in chronic pain trials . The tesDynamic balance was assessed using the FRT. Participants were asked to stand next to the wall while keeping their arms straight at shoulder level and reach forward as far as possible, without stepping. The distance between the length of the arm and a maximal forward reach was recorded in the standing position. Longer reaching distances indicate better dynamic balance .Back muscle endurance was evaluated by the modified Sorensen test which is the most widely used test in the literature for evaluating the isometric endurance of back extensor muscle. Participants were positioned prone on an examination table with the upper edges of their iliac crests aligned with the table’s edge. Both lower extremities were fixed to the examining table using three straps at the levels of the pelvis, knees, and ankles. With their arms folded across their chest, participants were instructed to hold their trunks at a horizontal position relative to the ground as long as possible. The time that the participant was able to hold the test position was measured in seconds. Maximum holding time was considered as endurance performance .Pain intensity was assessed using the visual analog scale (VAS). The scale is a self-administered measure, ranging from 0 points which indicates "no pain" to 10 points which indicates "maximum intensity of pain." The participants rated their current pain intensity using VAS .Pain-related anxiety was assessed via the Persian short-form version of the Pain Anxiety Symptoms Scale-20 (PASS-20) . The scaDisability was evaluated by the Oswestry Disability Index (ODI). The ODI is a self-administered, 10-item questionnaire designed to assess pain-related disability in individuals with LBP. Each item is scored on a 0–5 scale, with 0 demonstrating no disability and 5 demonstrating the greatest disability. Total score ranged between 0 to 100 percent and higher scores mean higher disability. The Persian version of ODI has shown reliability and validity properties in LBP subjects . AccordiAge, sex, height, and weight were recorded at baseline. All participants completed the Persian version of the VAS, ODI, and PASS-20, to collect pain intensity, disability, and pain-related anxiety information. For physical performance assessment, participants perform TUG, FRT, 6MWT, and modified Sorensen test at the same session in a random order. A five-minute rest time was considered between each test to minimize fatigue. All tests were performed by one experienced physiotherapist.α = 0.05, the effect size of f = 2.5, and the total number of predictors and covariates as 8, the required sample size would be 69. Considering 15% dropout, 80 patients were included.The sample size was calculated with G*Power, version 3.1.9.2 for a linear multiple regression model. From a priori analysis, with a power of 80%, Data analysis was performed using SPSS software, version 26. Numerical data was expressed as mean and standard deviation, while categorical data was presented as frequency and percentage. The normality of the data was verified using a combination of histograms, the Shapiro‐Wilks test, and skew/kurtosis. The independent t-test was used to compare study variables between groups with high and low disability.To evaluate the bivariate correlation between physical performance, pain-related anxiety, and disability, Pearson’s correlation was used.A multivariable linear regression analysis was performed to evaluate the contribution of dependent variables  with the independent variable (disability) in patients after lumbar decompression surgery. To control for demographic variables  that could be associated with disability, these variables were selected priori as potential covariates. Only variables with significant bivariate correlation were included in the model. Before performing linear regression analysis, the required assumptions were tested: linearity (scatterplots), normality of dependent variable, and homoscedasticity were tested by plotting the residuals versus the fitted values, and the presence of multicollinearity was determined by a variance inflation factor > 3. The correlation between all independent variables used in the regression analysis was < 0.80. All variables with significant correlations with ODI score were included in a multivariable linear regression analysis. Standardized β values are presented to reflect the direction and strength of the association between each independent variable.p < 0.05.Finally, a stepwise regression analysis was performed with the disability as the dependent variable and only the significant independent variables from the preliminary multivariable analysis. The level of statistical significance was set at t-test showed that there was no significant difference in age and BMI between groups. Individuals with high disability showed significantly higher TUG test time, and lower FRT scores compared to low disability individuals. Moreover, individuals with a higher disability had lower modified Sorensen test times as well. No significant between-group differences were observed for 6MWT scores. In addition, higher PASS-20 scores and greater pain intensity in both low back and lower extremity regions were observed in high-disability individuals.Eighty individuals who underwent lumbar decompression surgery were included. According to the normality tests, the distribution of data was normal. Table r = − 0.75). Table The results of bivariate association revealed a significant relationship between physical performance (FRT and modified Sorenson), VAS, and PASS-20 with disability, except 6MWT which showed no significant association. In addition, the strongest association was observed between disability and PASS-20 , explaining around 68% of ODI variance. Among these predictors, PASS-20 was the strongest predictor of ODI.All tested assumptions met the criteria for conducting a linear regression analysis. Table Only the significant independent variables used in the multivariable regression analysis were included in the stepwise regression. Stepwise regression analysis Table  revealedThis study aimed to describe the association between disability and physical performance, pain intensity, and pain-related anxiety among patients 6–12 months post-lumbar decompression surgery. The results revealed significant relationships between disability and pain-related anxiety, the FRT, and the modified Sorensen test scores in patients after lumbar decompression surgery. Pain-related anxiety was the strongest indicator of disability.The findings showed that high levels of pain-related anxiety had the strongest association with disability. However, the level of pain intensity was not an indicator of disability. This might explain the importance of psychological factors as an indicator of long-term disability post-lumbar surgery. This finding is consistent with previous studies that reported a cumulative negative effect of different elevated psychosocial factors  on long-term disability , 18. MorAlthough the results of bivariate correlation support the association between disability and pain intensity, this association was not confirmed when other variables were entered into multivariable analyses. This finding demonstrates that high levels of pain-related anxiety, back muscle endurance (assessed by the modified Sorensen test), and dynamic balance (assessed by FRT) were more likely to be associated with disability. An assessment 6–12 months after lumbar decompression surgery may explain the lack of association between pain and disability. This may reflect that patients are experiencing symptom improvement, 6–12 months post-lumbar decompression surgery.Disability was found to be associated with back muscle endurance (assessed by the modified Sorensen test) and dynamic balance (assessed by FRT). Also, the results of bivariate analysis revealed a strong positive association between modified Sorensen test scores and FRT scores in patients' post-lumbar decompression surgery. Performance of the Sorensen test and FRT involves trunk control and depends on back muscle endurance and strength , 20. In The results also revealed that while modified Sorensen test and FRT scores were strongly correlated with disability, TUG and 6MWT scores had no statistically significant correlation with disability. This finding aligns with previous research, which identified TUG test scores after lumbar decompression surgery was within the normal population range . ModifieThe results confirm that pain-related anxiety has the potential to improve disability in patients after lumbar decompression surgery; however, there is a need for additional targets to also improve back muscle endurance and dynamic balance, which are important aspects of physical performance.The present study has some limitations. First, despite using valid and reliable questionnaires, the self-reported nature of the questionnaires might have led to recall bias. Second, the association of other psychological factors with disability  was not assessed. Finally, the cross-sectional design of the study limits the evidence level of the findings.The presence of an association between disability and pain-related anxiety, and some aspects of physical performance  was supported in patients 6–12 months after lumbar decompression surgery. However, the association between disability and pain intensity, and some aspects of physical performance  could not be confirmed.The results suggest that pain-related anxiety should be considered in the rehabilitation programs of patients after lumbar decompression surgery. Also, exercise programs that focus on back muscle endurance and dynamic balance may be crucial after lumbar decompression surgery. Moreover, a comprehensive evaluation of all aspects of physical performance is suggested in patients after lumbar decompression surgery.


Background and Objectives: Through a comprehensive meta-analysis of the pertinent literature, this study evaluated the utility and efficacy of perioperative infraorbital and/or infratrochlear nerve blocks in reducing postoperative pain and related morbidities in patients undergoing septorhinoplasty. Materials and Methods: We reviewed studies retrieved from the PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to August 2023. The analysis included a selection of seven articles that compared a treatment group receiving perioperative infraorbital and/or infratrochlear nerve blocks with a control group that either received a placebo or no treatment. The evaluated outcomes covered parameters such as postoperative pain, the amount and frequency of analgesic medication administration, the incidence of postoperative nausea and vomiting, as well as the manifestation of emergence agitation. Results: The treatment group displayed a significant reduction in postoperative pain , as well as a significant decrease in both the amount  and frequency  of analgesic medication use compared to the control. The incidence of emergence agitation  was notably lower in the treatment group. The incidence of postoperative nausea and vomiting  showed a trend towards reduction, although it was not statistically significant. While no adverse effects reaching statistical significance were reported in the analyzed studies, hematoma  and edema  after blocks appeared at rates of approximately 20%. Conclusions: Infraorbital and/or infratrochlear nerve blocks for septorhinoplasty effectively reduce postoperative pain and emergence agitation without notable adverse outcomes. Septorhinoplasty is a surgical procedure designed to improve the aesthetic features of the nasal region and correct any deformities. The postoperative phase can often involve significant discomfort, which arises from factors such as soft tissue trauma, irritation of periosteal tissues, and the effects of interventions on bones, including osteotomies ,2. MoreoThe infraorbital nerve, a branch of the maxillary division of the trigeminal nerve, plays a pivotal role in providing sensory innervation to the cutaneous areas around the nose and the nasal septum . The infHowever, the effect of infraorbital and/or infratrochlear nerve blocks on the peri-nasal region remains a topic of debate ,15. We hhttps://osf.io/r3jve/ (accessed on 13 August 2023).This systematic review and meta-analysis was conducted in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . The resThe criteria, based on Population, Intervention, Comparison, Outcomes, and Study (PICOS), are as follows: (1) Population: patients who underwent septorhinoplasty; (2) Intervention: perioperative infraorbital and/or infratrochlear nerve blocks; (3) Comparison: either a placebo or no treatment; (4) Outcomes: grading of postoperative pain as reported by patients, quantity, and frequency of administered analgesic drugs, instances of postoperative nausea and vomiting and emergence agitation, and any events of adverse effects related to the infraorbital and/or infratrochlear nerve blocks; (5) Study design: not specified. Clinical studies up until August 2023 were sourced from PubMed, SCOPUS, Google Scholar, Embase, and the Cochrane Register of Controlled Trials. Key search terms employed included ‘nerve block’, ‘rhinoplasty’, ‘septorhinoplasty’, ‘infraorbital nerve’, ‘infratrochlear nerve’, ‘pain’, ‘emergency agitation’, ‘nausea’, and ‘adverse effect.’ Detailed search terms and queries are listed in To qualify for the review, studies had to meet specific criteria: they needed to involve patients undergoing septorhinoplasty and the application of an intraoperative infraorbital block. Studies focusing on additional procedures, such as sinus surgery, were excluded, ensuring the emphasis remained on septoplasty. Any research not offering clear, measurable data related to the outcomes of interest, or where extracting valuable information from the published results was impractical, was not considered. Data from qualifying studies were extracted using standardized data collection forms ,18,19. Tp-values denoting the contrast between the treatment and control groups, as outlined in the chosen studies. This thorough data aggregation aimed to uncover the potential influence of the nerve block on postoperative complications and adverse effects.The data chosen for analysis encompassed patient demographics, pain intensity ratings given by patients, specifics regarding analgesic drug usage in terms of amount and regularity, rates of postoperative nausea and vomiting, events of emergence agitation, occurrences of side effects, and the stated A statistical evaluation of the included studies was performed using the R-4.3.1 program developed by the R Software 4.3.1 Foundation based in Vienna, Austria. For quantitative variables, the meta-analysis was performed using either the standardized mean difference (SMD) or mean difference (MD). Employing SMD as a summary statistic allowed for the alignment of study outcomes onto a consistent scale, particularly when evaluations of similar outcomes were achieved using varied methods. This approach was chosen to gauge the quantity of administered analgesic medication, due to the lack of a universal scale across all studies. MD, indicating the average variance between the treatment and control groups, was calculated when the outcomes across studies were consistent and conveyed in similar units within the patient-reported pain grading scale. For metrics such as the regularity of analgesic medication administration, the incidence of postoperative nausea and vomiting, events of emergence agitation, and recorded side effects, the odds ratio (OR) was determined.2 test, which describes the degree of variance across studies attributable to reasons beyond random chance, with values ranging from 0 (indicating no heterogeneity) to 100 (representing maximum heterogeneity). All reported findings were paired with a 95% confidence interval (CI), and p-values were cited for two-tailed tests. If significant heterogeneity in outcomes was detected, indicated by I2 > 50, the random-effects model, following the DerSimonian–Laird method, was adopted. This model assumes different variances in true treatment effects among studies and anticipates a normal distribution of these. Where needed, subgroup analysis was also undertaken. Situations where heterogeneity was not significant, indicated by I2 < 50, were examined using the fixed-effects model. This model, leveraging the inverse variance method, assumes a common source for all studies within the evaluated population.Heterogeneity was evaluated using the ITo identify possible publication bias, both a funnel plot and Egger’s test were utilized. The Duval and Tweedie’s trim-and-fill method was also applied to adjust the combined effect size, accounting for any perceived publication bias. Moreover, sensitivity analyses were conducted to gauge the impact of individual studies on the overall meta-analysis results, which involved performing repeated meta-analyses, each time excluding one specific study.p = 0.4912). However, it is worth noting that an assessment of publication bias for other outcomes was not conducted due to the limited number of studies available, which made the creation of a funnel plot infeasible.We evaluated a total of seven studies encompassing 414 participants. Detailed information about the individual studies is provided in 2 = 98.8%), and quantity  and frequency  of administered analgesics, in the treatment group were markedly lower than the values in the control group, as shown in 2 > 50%) was observed in the mentioned outcomes.The postoperative pain score , the interval after surgery when the pain score was assessed , or the criteria for administering analgesics (a pain score > 3 or >7). This lack of differentiation likely contributed to the high heterogeneity (>50%) observed across all studies’ results.2 = 98.9%; 2–8 h: 2.4546 , I2 = 99.3%; 8–24 h: −1.6588 , I2 = 98.6%; 2 days: −0.5000 , I2 = NA) (p = 0.1895). These findings suggest that infraorbital and/or infratrochlear nerve blocks might maintain their efficacy up to 2 days postoperatively.In a subgroup analysis that evaluated postoperative pain relative to the elapsed time, no significant variances were observed among the different time intervals  was significantly less than the amount decided by clinicians  (p < 0.0001). It is worth noting that postoperative pain intensity typically peaks within the first 24 h following surgery, with this pain often intensifying during the evening , IAn iterative sensitivity assessment was performed, wherein individual studies were consecutively excluded from the meta-analysis. No single study was found to significantly impact the overall trend.Our meta-analysis demonstrates that perioperative pain management utilizing infraorbital and/or infratrochlear nerve blocks effectively reduced postoperative pain and the usage of analgesic drugs. Moreover, there was a significant decline in the incidence of emergence agitation. Importantly, there were no notable adverse effects, including neurological deficits, reported.Postoperative pain is characterized as acute inflammatory pain that originates with surgical trauma and typically resolves in tandem with tissue healing. When pain triggers a release of catecholamines, it can precipitate cardiovascular incidents, undesirable neuroendocrine or metabolic changes, thromboembolic events, pulmonary complications, and prolonged hospital stays . It is cEmergence agitation is a postanesthetic phenomenon marked by psychomotor behaviors such as agitation, confusion, disorientation, and potential aggressive conduct that occurs during recovery from general anesthesia ,25. ThisNonetheless, achieving effective analgesic management remains a significant challenge. Postoperative pain affects a vast segment of the global population. The postoperative period inherently carries an increased likelihood of morbidity and mortality, with some cases potentially attributed to the use of analgesic agents ,28,29. SConsequently, many patients often undergo treatment using a mix of non-opioid analgesic agents, a strategy known as multimodal analgesia . The maiPeripheral nerve blocks involve the injection of a local anesthetic near the nerve that serves the surgical area. These anesthetics work by changing the sodium permeability of cell membranes, effectively halting nerve impulse transmission and leading to pain relief . A distiOur findings suggest that infraorbital and/or infratrochlear nerve blocks administered to patients undergoing septorhinoplasty provide effective pain control with minimal complications and reduce the reliance on perioperative opioids. Furthermore, the use of ultrasound guidance may increase the efficiency and safety of the procedure ,42. It iHistorically, efforts to alleviate emergence agitation have mainly centered on pharmacological solutions. Drugs such as ketamine, dexmedetomidine, and propofol have been found to be effective for managing emergence agitation in adults. However, it is worth noting that relying on pharmacological prevention can lead to prolonged sedation and hemodynamic changes, including hypotension, hypertension, and bradycardia. Such outcomes could result in extended durations in the Post-Anesthesia Care Unit, prompting considerations about cost-efficiency.In the context of our research, we primarily concentrated on pain control using peripheral nerve blocks. As such, we champion the adoption of a multimodal pain management strategy, integrating systemic analgesics with peripheral nerve blocks, as the recommended method for septorhinoplasty when appropriate. Additionally, when performing septorhinoplasty, office-based local anesthesia can be facilitated by pain control caused by nerve blocks, and clinical data on this will also be needed.However, this study is not without its limitations. Despite thorough subgroup analyses, fully addressing the heterogeneity regarding the effect of the perioperative nerve blocks on procedural morbidities was challenging. Several factors contribute to these challenges. First, the use of various local anesthetic agents in different studies, including levobupivacaine, ropivacaine, and bupivacaine, introduces variability. It is essential to note that the clinical characteristics of levobupivacaine and ropivacaine are similar to those of racemic bupivacaine, with differences mainly related to slight variation in anesthetic potency. Specifically, racemic bupivacaine displays higher potency compared to levobupivacaine and ropivacaine . Second,This study underscores the efficacy of infraorbital and/or infratrochlear nerve blocks for septorhinoplasty in mitigating postoperative pain and emergence agitation. Furthermore, the application of this intervention did not present significant adverse outcomes, such as neurological deficits.