ObjectivesAnalgesic drugs are commonly used to alleviate the pain experienced by palliative care (PC) patients. Thus, we sought to determine the prescription patterns of analgesic drugs in the management of pain among haematology and oncology palliative care patients at Sultan Qaboos University Hospital (SQUH) and then see if they were following the World Health Organization (WHO) guidelines.MethodsA retrospective observational cross-sectional study was conducted, and adult PC patients prescribed analgesics for pain relief between January 2018 and January 2021 at SQUH constituted the sample. Data were collected from patients' electronic medical records using the SQUH TrakCare system. The data was then presented descriptively using graphs and tables.ResultsData from 200 PC patients were analyzed. Breast cancer was the most common malignancy, with 73 (36.5%) patients diagnosed with it. Severe pain was the most reported degree of pain, with exactly 100 (50.0%) patients experiencing it. More patients experienced mild pain than moderate pain. Opioids were the most prescribed analgesics, followed by analgesics and antipyretics, anticonvulsants, and finally non-steroidal anti-inflammatory drugs (NSAIDs). Paracetamol was the most prescribed analgesic for pain overall, with 127 (63.5%) patients utilizing it. For severe pain, morphine was the most prescribed analgesic, with 65.0% of patients using it. Fentanyl and pregabalin, the strongest two analgesics, increased in prescription for severe pain compared to mild and moderate pain, with both being prescribed to 23.0% of patients suffering from severe pain. The oral route of administration was the most prescribed, with 128 (64.0%) utilizing it.ConclusionThis study showed the prescription patterns of analgesic drugs for palliative care patients at SQUH. The findings were similar to those of other studies, though there were some differences. The prescription patterns of analgesic drugs prescribed for the various pain levels among PC patients were found to be in accordance with the WHO guidelines. Palliative care (PC) is a treatment approach aimed at improving the quality of life of patients with life-threatening illnesses through the prevention and relief of their pain . PalliatMany diseases are associated with palliative care patients, including advanced cancer, chronic obstructive pulmonary diseases (COPD), congestive heart failure (CHF), and end-stage renal diseases, with cancer specifically being the most common one . PalliatAnalgesic drugs, commonly referred to as painkillers, work to alleviate a patient's pain. There are many ways to classify analgesic drugs; one classification is based on the receptor they act on. These include opioids and non-opioids. Opioids include codeine, morphine, fentanyl, and methadone; non-opioids include paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) . AnotherThis study aimed to identify the prescription patterns of analgesic drugs among oncology and hematology palliative care patients at Sultan Qaboos University Hospital (SQUH) and then compare those findings with those of other hospitals worldwide. The rationale for conducting this project is that there is limited data currently on the analgesic drug prescription patterns in Oman, so this study would fill the gap through the experience of a single center (SQUH). In addition, the findings of this study give healthcare providers in Oman a clear picture of the current prescription practices and allow them to determine if there needs to be any modification or improvement to them. Lastly, the findings of this project will also provide a platform and basis for comparison with other hospitals and centers worldwide. Ultimately, this could all lead to improvements in the quality of healthcare in Oman and improvements in the patient's quality of life.This study is a retrospective observational cross-sectional study conducted at Sultan Qaboos University Hospital, Muscat, Oman. Adult patients (≥ 18 years) with palliative conditions who were prescribed analgesics between January 2018 and January 2021 were eligible for this study. In addition, only PC patients whose diseases were of oncological or hematological origin were considered, as many hospitals worldwide group oncology and hematology patients under one unit rather than separating them, so this would allow for a more accurate comparison. Patients initially admitted for PC who no longer needed it were excluded from this study. Data was extracted through the patients' medical records using the SQUH TrakCare system and included the following: demographic data, medical history, diagnosis, severity of pain as reported through the clinical notes, outcome, and details of prescribed analgesics.Using the sample size for the population mean formula at a confidence level of 95% and a margin of error of 5%, a total sample size of 195 patients was required for this study; however, data from 200 patients was collected. The collected data was analyzed using IBM SPSS Statistics for Windows, Version 27.0 . The data was presented as the mean with the standard deviation (SD), percentages, and range. Variables such as drug classes, routes of administration, opioid combinations, and many others were considered categorical data. Ethical approval was obtained from the Medical Research and Ethics Committee (MREC #2508) at the College of Medicine and Health Sciences, Sultan Qaboos University.Data from 200 patients was collected, of whom 81 (40.5%) were males and 119 (59.5%) were females. The mean age of the patients was 59.00 ± 13.60 years, with the youngest patient being 24 years of age and the oldest one being 93. Patients with an oncological malignancy made up most of the sample, representing 95.50%. In contrast, patients with hematological malignancies made up the remaining 4.50% of the sample. None of the patients in the sample had both malignancies. Severe pain was the most reported regarding pain levels, with exactly 100 (50.0%) patients experiencing it. More patients experienced mild pain than moderate pain, with 58 (29.0%) patients experiencing mild pain and 42 (21.0%) patients experiencing moderate pain, respectively. The outcome of death was higher than discharge, with 104 (52.0%) patients passing away. Hypertension was the most commonly reported comorbidity, with 34.5% of the sample hypertensive. The demographic data of the sample is displayed in Table As shown in Figure As per Table Figure In Figure As for severe pain, in Figure The oral route of administration was the most prescribed, with 128 (64.0%) patients utilizing it. This was followed by the intravenous IV route utilized by 92 (46.0%) patients. Lastly, the transdermal route was utilized by 27 13.5%) patients, as only fentanyl is available as a transdermal formulation  in Oman. Regarding the socio-demographic profile, specifically gender, female patients (59.5%) were more prevalent than males (40.5%) in the current study. A study that explored the preference for palliative care in cancer patients found that females were three times more likely to consider palliative care than males . This saPain is the most common symptom experienced by palliative care patients . A studyIn the present study, patients with hematological and oncological malignancies were considered. Patients with oncological malignancies were much higher and represented most of the sample at 95.5%. This could be because cancer is the most common disease among palliative care patients . AnotherIn terms of cancer, breast cancer was the most common (36.5%), followed by colorectal cancer 13.0%). Breast cancer is the most common in Oman, followed by non-Hodgkin lymphoma and colon cancer [3.0%. BreAnalgesic drugs are the most prescribed drugs for palliative care patients . As per Multiple routes of administration are available for analgesic drugs. In our study, three routes of administration were utilized: the oral route (64.0%), the IV route (46.0%), and the transdermal route (13.5%). The literature supports those findings, which suggest that the oral route is the most common and preferred method due to its cost-effectiveness, convenience, and lack of invasiveness . In addiThough this study was only intended to focus on a single center (SQUH), the findings cannot be generalized to all the hospitals in Oman. In addition, only analgesic drugs from the most recent admission were considered; thus, there may be differences with previous admissions. One other limitation is the idea of prescription vs. utilization. What is prescribed is not necessarily utilized, as some patients may not be compliant; therefore, this may cause some errors . Lastly, the retrospective nature of this study may result in some missing past data and the loss of some patients on follow-up.It is recommended that similar retrospective studies be conducted in other hospitals in the country and the region. In addition, a prospective study on this topic may be conducted using the Edmonton Symptom Assessment System tool . SimilarAnalgesics are the most commonly prescribed medications among PC patients worldwide. Different hospitals in the region have different prescribing patterns, and so this study explored the prescription patterns of analgesic drugs for PC patients at SQUH specifically.From the data collected through the SQUH TrakCare system, it was found that cancer, specifically breast cancer, was the most common disease among the sample. Paracetamol was the most prescribed analgesic drug overall, whereas morphine was the most prescribed drug for severe pain. The oral route of administration was the most utilized. This study's findings were similar to those of other hospitals in the region and worldwide, though there were some minor differences. In addition, the drugs prescribed for the various pain levels are in accordance with the WHO guidelines, as observed through the comparison with the WHO analgesics ladder, demonstrating the significance of this study's findings. Since many other life-threatening diseases could require PC, future studies could focus on the prescription patterns of analgesics for those diseases, beyond this study's scope, which focused purely on cancer and hematological diseases. Furthermore, future studies can evaluate the prescribing patterns among other tertiary hospitals in Oman, evaluating their similarity to SQUH and the WHO guidelines.


This study evaluated the effect of continuous erector spinae plane block on both acute and chronic postthoracotomy pain, and it was safe and effective. Postthoracotomy pain (PTP) is a severe pain complicating thoracic surgeries and its good management decreases the risk of PTP syndrome (PTPS).This randomized controlled study evaluated the efficacy of ultrasound-guided continuous erector spinae plane block (ESPB) with or without dexmedetomidine compared with thoracic epidural analgesia (TEA) in managing acute postoperative pain and the possible emergence of PTPS.Ninety patients with chest malignancies planned for thoracotomy were randomly allocated into 3 equal groups. Group 1: TEA , group 2: ESPB (20 mL of levobupivacaine only 0.1% bolus every 6 hours), and group 3: ESPB (20 mL of levobupivacaine 0.25% and 0.5 μg/kg of dexmedetomidine Hcl bolus every 6 hours).Resting and dynamic visual analog scales were higher in group 2 compared with groups 1 and 3 at 6, 24, and 36 hours and at 8 and 12 weeks. Postthoracotomy pain syndrome incidence was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. The grading system for neuropathic pain score was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. Itching, pruritis, and urine retention were higher in group 1 than in ESPB groups.Ultrasound-guided ESPB with dexmedetomidine is as potent as TEA in relieving acute PTP and reducing the possible emergence of chronic PTPS. However, the 2 techniques were superior to ESPB without dexmedetomidine. Erector spinae plane block has fewer side effects compared with TEA. Thence, the count of chest procedures and postthoracotomy pain syndrome (PTPS) continuously rises. Postthoracotomy pain syndrome prevalence could reach 30% to 50%.21 The pain of PTPS is described as moderate to severe in one-fourth of cases and follows both open and video-assisted thoracotomies. It could impair sleep, the patient's psyche, activities of daily living, and overall quality of life (QOL).30 Postthoracotomy pain (PTP) may arise from the rib–periosteal–intercostal nerve complex, yet injury of the intercostal nerve is the main concern in emerging neuropathic PTPS.47 Postthoracotomy pain syndromes has several components, the neuropathic one being the cornerstone with myofascial and other pain generators.32Lung cancer represents approximately 13% of cancer patients and accounts for a high percentage of cancer-related mortality.46The most critical risk factor for developing PTPS is severe unrelieved postoperative pain . Therefore, several locoregional and neuraxial techniques have been tried and implemented in multimodal analgesia for that purpose, including thoracic epidural analgesia (TEA), paravertebral block (PVB) besides serratus anterior plane block (SAPB), and recently erector spinae plane block (ESPB).38Several interventional modalities have been described for treating this type of refractory pain syndrome, such as intrapleural analgesia, intercostal blocks, TEA using steroids, PVB, thoracic sympathectomies, radio frequency therapy of dorsal ganglia, intrathecal drugs delivery, and spinal cord stimulation.16 Recently, locoregional analgesic techniques have been successfully used to manage PTPS, including ESPB.13Postthoracotomy pain syndrome is pain that recurs or persists at the thoracotomy scar at least 2 months after the surgery without infection or cancer recurrence.34 However, TEA has several adverse effects, such as hypotension, motor blockade, hematoma, and abscess. Thoracic paravertebral block has a chance of epidural spread and pneumothorax, and multiple injections are needed if more than 4 dermatomal analgesics are required.48Thoracic epidural analgesia and thoracic paravertebral block (TPVB) are the most used techniques for analgesia after thoracic surgery.26 Erector spinae plane block is a relatively simple technique with easily identified sonographic landmarks, and a catheter is easily inserted into the plane after distention induced by the injection. In addition, the ESPB has the potential to provide both somatic and visceral sensory blockade.26Recently, ESPB was reported as a treatment for thoracic neuropathic pain.2-receptors is 8 times of its prototype, clonidine. Accordingly, dexmedetomidine has more powerful sedative and analgesic effects than clonidine, with fewer hemodynamic derangements because of α1-receptor activation.6 Dexmedetomidine has been primarily used for sedation in intensive care settings. The unique analgesic properties of dexmedetomidine have encouraged anesthesiologists to use it perineurally. Previous studies have declared that dexmedetomidine potentiates local anesthetic effects when administered by the neuraxial route.14 This study aims to evaluate the efficacy of ultrasound-guided continuous ESPB with or without dexmedetomidine compared with TEA in managing acute postoperative pain and possible emergence of PTPS.The selectivity of dexmedetomidine to the αclinicaltrials.gov under the registry (NCT04531553). The study was conducted following the Helsinki Declaration. After explaining the procedure and obtaining written formal consent, we included 90 patients of both sex scheduled for thoracotomy for thoracic cancer surgeries under general anesthesia  with the American Society of Anesthesiologists physical status classification I and II, age ≥18 and ≤65 years, and body mass index (BMI) between 20 and 40 kg/m2. The exclusion criteria were patient refusal, known sensitivity or contraindication to local anesthetics or dexmedetomidine, history of psychological disorders, localized infection at the site of block, and uncorrectable coagulopathies .This prospective, randomized, controlled, double-blinded study was conducted in Egypt from Mach 2021 to June 2022. The study was approved by the local institutional review board (IRB Number: 201920015.2P) and registered at All included patients were randomly divided into 3 equal comparable groups using computer-generated random numbers; each included 30 patients.Group 1 (n = 30): patients preoperatively received a TEA at the level T5 and T6 with a bolus of 20 mL of levobupivacaine  0.25%, then levobupivacaine 0.1% infused at a rate of 0.1 mL/kg/h until chest tube removal .Group 2 (n = 30): patients preoperatively received US-guided ESPB on the same side, that is, scheduled operative side, the puncture point of the skin was infiltrated with 2% lidocaine, and once the structures were identified with ultrasound at the level of T5 transverse process, a bolus of 20 mL of levobupivacaine 0.25% was injected on the deep aspect of erector spinae muscle with catheter insertion. A 20 mL of bolus of levobupivacaine 0.1% was injected every 6 hours until chest tube removal.Group 3 (n = 30): with the same procedure as group 2, the patients received a bolus of 20 mL of levobupivacaine 0.25% and 0.5 μg/kg of dexmedetomidine Hcl  on the deep aspect of erector spinae muscle, then catheter insertion; 20 mL bolus of levobupivacaine 0.1% with dexmedetomidine 0.5 μg/kg was injected every 6 hours until chest tube removal.All patients were assessed the day before surgery in a preoperative visit to evaluate their medical status and laboratory investigations and to fulfil all the inclusion and exclusion criteria mentioned above. The patients were instructed on how to report pain using the visual analog scale (VAS) score rating, in which 0 = “no pain” and 10 = “worst possible pain.”With aseptic conditions under LA, the epidural space was identified(T5-T6 in midline approach) in sitting position using 18-G Tuohy needle by the loss of resistance to air technique. Then, an 18-G Portex epidural catheter was inserted 5 cm beyond the needle tip and the needle was removed. After checking the patency of the catheter, the catheter was fixed with a fixator, and 2 mL of 0.25% levobupivacaine was given as a test dose. Then, the patient placed in the supine position then another 18 mL of 0.25% bupivacaine was given.11 The patient was placed in a sitting position under complete aseptic condition, and a cover sheath was used for the ultrasound probe with an appropriate amount of lubricating gel applied on the probe, a high-frequency, linear, ultrasound transducer placed in a longitudinal orientation 3 cm lateral to the T5 spinous process. This should reveal 3 superficial muscles to the hyperechoic transverse process shadow: trapezius, rhomboid major, and erector spinae. The skin was anesthetized using 3 mL of 2% lidocaine. A 17‐G, 89‐mm R‐X Coudé epidural needle  was inserted in plane in a cephaled-to-cauded direction to place the tip into the fascial plane on the deep (anterior) aspect of erector spinae muscles, and 20 mL of levobupivacaine 0.25% or a mixture of 20 mL of levobupivacaine 0.25% with 0.5 μg/kg of dexmedetomidine was injected. The injectate included 5 mL of contrast medium iohexol 180 mg I/mL   machine and an HFL38X linear transducer (Sonosite Inc) 13 to 16 MHZ.The success of the block was confirmed by the loss of pinprick sensation on the dermatomal site of the block after 30 minutes of injection, and patients with a failed block were excluded.2 = 50%), and top-up doses of IV rocuronium (0.1 mg/kg) were administered as required. All patients received 1 gm of IV paracetamol. Additional bolus doses of 0.5 µg/kg of fentanyl were given if the mean arterial blood pressure or heart rate rose above 20% of baseline levels and calculated. Patients were mechanically ventilated at appropriate settings that keep end-tidal CO2 at 30 to 35 mm Hg. One reading of mean arterial pressure and heart rate was taken before induction of general anesthesia to be defined as a baseline reading and then regularly recorded immediately before surgical incision and at 30-minute intervals intraoperatively. By the end of the surgery, the residual neuromuscular blockade was reversed using Sugammadex (2 mg/kg), and extubation was performed after complete recovery of the airway reflexes.Premedication with 0.02 mg/kg of midazolam was administered intravenously 30 minutes preoperatively. All included patients were monitored continuously using electrocardiography, noninvasive blood pressure, peripheral oxygen saturation, and end-tidal carbon dioxide—using the Datex-Ohmeda S5 anesthesia monitor, model no: USE1913A—throughout the surgical procedure. Induction of anesthesia was performed for all groups using a regimen of 2 μg/kg of IV fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of rocuronium. Anesthesia was maintained with inhaled sevoflurane with MAC 2% to 2.5% in oxygen-enriched air (FiOAll patients were transferred to the postanesthesia care unit where pain scores (VAS), MAP, and heart rate were recorded immediately on arrival, then at 2, 4, 6, 12, and 24 hours postoperatively. The patients were observed in the postoperative care unit for 2 hours, and rescue analgesia was provided as IV morphine 0.1 mg/kg per dose (max 0.3 mg/kg/d) boluses if the pain score was >3. The total amount of morphine given in 24 hours was recorded in the 3 groups. After that, the patients were shifted to the ward, and IV acetaminophen 1 g every 8 hours was prescribed.3 ; 0.1 mg/kg of IV ondansetron was given to patients with moderate or severe postoperative nausea and vomiting.Any adverse effects such as nausea, vomiting, hypotension, bradycardia, oversedation, or hematoma were recorded. Postoperative nausea and vomiting (PONV) were rated on a four-point verbal scale(1) Duration of the procedure, ICU stay, total hospital stay duration, pathology, lung resection procedure , baseline quality of life scale (QOLS), and pre/postoperative chemo/radiotherapy.(2) VAS score was the primary outcome; it is a horizontal 10‐cm line with zero on the left end indicating no pain and 10 cm on the right end indicating the worst imaginable pain. The average VAS was assessed every 6 hours in the first 24 hours, and then, the average VAS was assessed daily in the first week . The average VAS values were also assessed at 2, 3, 4, 8, and 12 postoperative weeks.39(3) Assessment of the possible emergence of PTPS (PTPS incidence) at weeks 8 and 12. The neuropathic PTPS cases were screened using the grading system for neuropathic pain 0 means NO, 1 means possible, 2 probable, and 3 definite positive. Patients with a neuropathic component grade 2 (probable) or 3 (definite) are considered having PTPS.All measured data were collected by an on‐duty ICU resident unaware of the study.19(4) Quality of life was assessed using the Flanagan QOLS, a 16‐item (domain) questionnaire with each item scored from 1 to 7 points. The scale was explained to the patients by the pain physician, and the total score was calculated and recorded at the preoperative assessment (baseline) and postoperative weeks 2, 3, 4, 8, and 12.18(5) The activity level was assessed using the Barthel activities of daily living scale (ADL) at postoperative weeks 2, 3, 4, 8, and 12. This scale comprises 10 basic daily activities , with each item scored as 0 = need complete help, 1 = need some help, or 2 = need no help.(6) The incidence of adverse events was recorded in all groups.(7) Intraoperative and postoperative opioid consumption was recorded in all groups.All patients requiring pain therapy were followed up at the pain clinic. Patients with neuropathic thoracic pain were treated according to the local institutional protocol. From the second postoperative week, pain therapy was offered in the form of adjuvant therapy  plus analgesics “paracetamol or NSAIDs (VAS < 40 mm), tramadol HCl 100 to 600 mg/d (VAS: 40–70 mm), and oxycodone 20 to 80 mg/d  (VAS ≥ 70 mm).”The sample size calculation was done by G*Power 3.1.9.2 . We performed a pilot study (5 cases in each group), and we found that the mean (±SD) of resting VAS at 12 hours was 2.4 ± 1.52 in group 1, was 3.4 ± 0.55 in group 2, and was 2.6 ± 1.34 in group 3. The sample size was based on the following considerations: 0.378 effect size, 95% confidence limit, 80% power of the study, 1:1 group ratio, and 18 cases were added to each group to overcome dropout. Therefore, we recruited 90 patients in each group.U) test was performed to compare every 2 groups. Categorial variables were expressed as frequency and percentage and were statistically analyzed by χ2 test. A 2-tailed P value of ≤0.05 was considered statistically significant.Statistical analysis was performed by SPSS version 25 . Shapiro–Wilks normality test and histograms were used to test the distribution of quantitative variables to select accordingly the type of statistical testing: parametric or nonparametric. Parametric variables were expressed as mean and standard deviation (SD) and were compared using the analysis of variance among the 3 groups with post hoc (Tukey) test to compare every 2 groups. Nonparametric variables  were expressed as the median and interquartile range (IQR) and were analyzed using the Kruskal–Wallis test; Mann–Whitney  and showed no significant difference between group 1 and groups 2 and 3. Postoperative morphine consumption was significantly higher in group 2 compared with group 1 and group 3  and showed no significant difference between groups 1 and 3 , which was controlled by the reassurance of the patients and liberal fluid intake; PONV (6/27 and 4/25), bradycardia (7/27 and 9/25), headache ; and uncomfortable thoracic hypoesthesia and numbness (2/27 and 2/25), no one of which required a reduction in the LA concentration.The current work compared TEA as the gold standard thoracic analgesic approach with an innovative, effective, locoregional, thoracic analgesic procedure “ESPB,” in controlling both acute and chronic PTP and their effect in reducing the emergence of chronic PTP syndrome “PTPS.” It showed that VAS values at both rest and movement were significantly higher in group 2 compared with groups 1 and 3 at 6, 24, 36 hours and at 8, and 12 weeks. The grading system for neuropathic pain was also higher in group 2 than in other groups at 8 and 12 weeks. Respectively, PTPS incidence was higher in group 2 compared with other groups at 8 and 12 weeks.27 The complex nature of thoracotomy pain implies the necessity of multimodal analgesia.29This study's results regarding the control of acute PTP and prevention of the emergence of PTPS showed that ESPB using dexmedetomidine added to local anesthetic was comparable to TEA. Both locoregional/neuraxial techniques confer multimodal analgesia, which is recommended by the American Society of Anaesthesiologists (ASA)—Task Force for managing acute postoperative pain “combined use of regional, intravenous, and oral analgesics.’39The grading system for neuropathic pain scoring was used to detect and evaluate the neuropathic component of PTPS. It has great value in defining PTPS “as one of the postsurgical pain syndromes” and localizing the neuroanatomical mapping of traumatic injury in the somatosensory nervous system.44 Yet, TEA problems like a technical failure are high (30%), sympathectomy-associated hemodynamic liability, opioid-induced nausea, vomiting, pruritis, urinary retention, and respiratory depression, besides risks of epidural hematoma or abscesses.35 Furthermore, this study protocol mandates extending postoperative pain control to 5 to 6 days for managing postoperative dorsal root ganglia (DRG) hyperexcitability and neuroplasticity.45 Most guidelines limit epidural analgesia to 3 to 5 days to reduce the potential hazards of bacterial colonization and infection.33 In addition, recent recommendations were to preserve TEA/PVB for midline and bilateral thoracotomies and to reserve locoregional analgesia for unilateral thoracotomies like ESPB.24 Moreover, many recent reports documented permanent neurological deficits after prolonged neuraxial block, mostly claiming to direct local anesthetics neurotoxicity.43For a long time, TEA was considered the gold standard for thoracotomy pain.23 It is a novel, relatively safe, and simple technique. It usually provides effective and immediate analgesia for many thoracolumbar procedures. Ultrasonographic guidance adds more practical value for this block because it involves drug injection away from neurovascular structures and the pleura.12 Moreover, the transverse process is a sonographic landmark and backstop for needle insertion, adding to the ease, efficiency, and safety of ESPB.Erector spinae plane block involves drugs injection either superficial or deep to ESM for thoracolumbar analgesia in both acute postoperative pain for thoracic surgeries, besides treating chronic and neuropathic pain conditions, eg, postmastectomy and PTP syndromes “PMPS-PTPS.”11 It was found that solutions of local anesthetics induce sensory multidermatomal (T3 up to T11) blockade across the posterior, lateral, and anterior chest walls because of the blocking of ventral, dorsal, and lateral rami of spinal nerve roots as injectate diffuses through medial, lateral, and craniocaudal directions in the interfascial planes, through the costotransverse foramen, the intervertebral foramina, and into the paravertebral and epidural spaces. In addition, ESPB may block the rami communicans of the sympathetic chain,22 which may explain the efficacy of ESPB in relieving somatic, visceral neuropathic, and myofascial components of PTPS.32Several cadaveric and multislice CT studies were performed to illustrate the spread of injectate in ESPB.31 In this study, installing the drugs deep into ESP was preferred to ensure more extensive and dynamic interfacial spread craniocaudally and depositing drugs near the ventral and dorsal rami of thoracic nerves to cover multiple dermatomes. This technique is similar to other techniques described for ESPB, for example, Forero et al.11 Furthermore, the targeted address here is the intercostal nerve, which is the cornerstone in initiating and maintaining neuropathic PTPS due to injury of the intercostal nerve–periosteal muscle complex during thoracotomies. In addition, ESPB is better practiced in parasagittal plane close to midline at the tip of T5 transverse process to be adjacent to the costotransverse foramina, allowing efficient craniocaudal spread of injectate. More laterally, the external and internal intercostal muscles may hinder the spread.The use of local anesthetic as Na-channel blockers added to the alpha 2 agonist “dexmedetomidine” in this study might eliminate the sustained peripheral input that induces abnormal central processing “central sensitization” of neuropathic component of pain.13 which could be attributed to the opening up of the potential interfacial spaces of ESP and adding more volumes to block different rami of thoracic nerve roots that usually outlasts the duration of action of local aesthetics blockade.32In this trial, the authors assumed that the use of radio-opaque, wire-loaded RACZ catheter to control the direction and distance of catheter threading under brief fluoroscopic guidance and adding contrast medium to the injected cocktail to verify dermatomal levelling could add to solidity and efficacy “in the author's opinion” of ESPB in both acute postsurgical pain control  and reducing the emergence of PTPS . The intermittent boluses injection is preferred over continuous infusion in the current trial and many other trials,12 who performed ESPB after epidural failure. Forero et al.11 also reported the benefits of ESPB in case series studying the treatment of PTPS and thoracic neuropathic pain.13 Chin et al.3 performed bilateral ESPB in 3 patients undergoing bariatric surgery at T7 transverse process. They postulated that efficient somatic and visceral abdominal analgesia was achieved.3 Tulgar et al.40 had documented similar visceral and somatic abdominal analgesia in laparoscopic abdominal surgery.40The current results showed comparable efficacy of ESPB with dexmedetomidine and TEA regarding VAS scores and less emergence of PTPS, shorter hospital stay, and fewer complications. These results are similar to the work of Forero et al.,36 it was concluded that the ESPB provides similar postoperative analgesia to the TEA regarding total postoperative fentanyl requirement and pain score in pediatric patients undergoing thoracotomy. The ESPB is simpler, faster, and has a lower complication rate.In this regard,8 it was reported that ESPB can be used as an effective and safe alternative to TEA for patients with lung cancer undergoing posterolateral thoracotomy.Moreover,41 also reported ESPB analgesia in geriatric patients with uncontrolled hypertension who underwent total hip arthroplasty. Pain relief was excellent for 2 days postoperatively, even with movement without adverse events.41 Erector spinae plane block reported effective analgesia for multiple rib fractures (T6–T9) even with cough and movement, resulting in rapid hospital discharge.20 Nagaraja et al.27 found that bilateral ESPB conferred lower VAS scores for 48 hours post cardiac surgery both at rest and with cough than continuous TEA with comparable ICU stay and postoperative complications. Eldemerdash and Abdelazeem et al.7 showed that pain relief was better with lower rescue morphine doses in ESPB than in PVB and serratus anterior plane block (SAPB) in patients who underwent breast surgeries under general anesthesia. Similar reports were documented by Bonvicini et al.2 who postulated that ESPB could be a safe alternative to TEA and PVB in reconstructive procedures for bilateral breast cancer. In addition, many trials suggested ESPB practice in the field of breast cancer surgeries because of its favorable values in postoperative analgesia, patient satisfaction, and opioid-sparing effect.49Tulgar et al.31 In addition, steroids have documented analgesic and antihyperalgesic benefits by expressing anti-inflammatory and inhibiting proinflammatory cytokines.4Further multicentric meta-analysis with a higher power sample size should verify the current data. The authors suggest that adding long-acting steroids to the injected mixture “even once before catheter removal” may reduce the continuous inflammatory process that propagates into persistent postsurgical pain and spontaneous ectopic neural discharge.Ultrasound-guided ESPB with dexmedetomidine is found to have the same potency as TEA in relieving acute post thoracotomy pain and reducing the possible emergence of chronic PTPS with a superiority to ESPB without dexmedetomidine. Erector spinae plane block has fewer side effects compared with TEA.The authors have no conflict of interest to declare.


Cancer-related pain affects a majority of patients with advanced cancer and is often undertreated. The treatment of this pain is largely reliant on the use of opioids, which are essential medicines for symptom management and the maintenance of quality of life (QoL) for patients with advanced cancer. While there are cancer-specific guidelines for the treatment of pain, widespread publication and policy changes in response to the opioid epidemic have drastically impacted perceptions of opioid use. This overview therefore aims to investigate how manifestations of opioid stigma impact pain management in cancer settings, with an emphasis on the experiences of patients with advanced cancer. Opioid use has been widely stigmatized in multiple domains, including public, healthcare, and patient populations. Physician hesitancy in prescribing and pharmacist vigilance in dispensing were identified as barriers to optimal pain management, and may contribute to stigma in the context of advanced cancer. Evidence in the literature suggests that opioid stigma may result in patient deviations from prescription instructions, which generally leads to pain undertreatment. Patients reflected on experiencing shame and fear surrounding their prescription opioid use and feeling uncomfortable communicating with their healthcare providers on these topics. Our findings indicate that future work is required to educate patients and providers in order to de-stigmatize opioid use. Through alleviating stigma, patients may be better able to make decisions regarding their pain management which lead to freedom from cancer-related pain and improved QoL. Pain is defined by the International Association for the Study of Pain (IASP) as an “unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage” , demonstThe population of patients with advanced cancer is largely understudied , and theThe goal of treatment for these patients is generally palliative, focused on the alleviation of symptoms, rather than curative-intent. In these cases, the healthcare system’s primary role is centered on providing symptom control and maintaining patient QoL throughout the disease trajectory. Due to a high prevalence of pain, coupled with increasing survival times and differing treatment priorities, barriers to effective symptom management are particularly impactful for patients with advanced cancer . This paA narrative review was completed using keyword searches on PubMed, EMBASE, and Google Scholar. Keywords included ‘cancer’, ‘malignant’, ‘metastatic’, ‘advanced’, ‘opioid’, ‘pain’, ‘cancer-related pain’, ‘pain management’, ‘stigma’, and ‘opiophobia’. Included articles focused on perceptions of opioid use for the treatment of pain among patients with advanced cancer. Abstract-only and non-English articles were excluded.Opioids are considered to be a gold-standard therapy for cancer pain management, and the World Health Organization (WHO) recommends them as the first choice for the treatment of moderate-to-severe CRP . OpioidsNorth America is facing an ongoing opioid epidemic which poses one of the most challenging and pressing public health issues of our time . The GovDespite the intended limited scope of updated guidelines, declines in opioid prescribing have been observed among oncologists in recent years ,32,33,34There is a variety of evidence indicating that there are significant differences between cancer and non-cancer populations in terms of the risks of opioid use. The lifetime prevalence of opioid-use disorder among non-cancer patients prescribed long-term opioid therapy has been estimated at 41.3% , compareWhile there are differences between cancer and non-cancer populations, consideration of the risks related to opioid use is still relevant when prescribing opioids to cancer populations. The older literature suggests that NMOU among patients with cancer is low compared to the general population ,41. HoweChronic opioid use, which may be a risk factor for NMOU , has beeFurther concerns for patients receiving opioid therapy include adverse effects such as the development of tolerance, physical dependence, cognitive dysfunction, constipation, and nausea . While tIn many cases, opioid dose escalations are required to maintain analgesic efficacy, which may be indicative of opioid tolerance or the pain hypersensitivity characteristic of opioid-induced hyperalgesia (OIH) ,54. In cAn additional consideration for opioid prescribing to patients with cancer involves the immunomodulatory effects of opioids and their potential impact on disease progression or metastasis. The literature on the role of opioids in cancer remains contested, largely due to the complexity of the direct and indirect interaction of opioids with immune functioning, inflammation, and metastasis . Long-teA lack of well-validated and specific information on the risks related to opioid use among patients with advanced cancer leaves patients and providers to guess and extrapolate regarding the trade-off between benefits and risks of opioid use. More research is required to understand these risks for patients with advanced cancer, as well as how they differ from broader cancer and non-cancer populations. This information could serve to alleviate uncertainty, which breeds fear and may be a contributor to stigmatization of opioids in this setting. The limited research on these outcomes means that implementation of a benefit-to-harm framework ,61 may nIn recent years oncology-specific guidelines have encouraged careful risk assessment when prescribing opioids to patients with advanced cancer ,62,63,64Risk assessment in this setting must additionally be considered with reference to issues of pain undertreatment. Under risk assessment recommendations, oncologists’ assessment of risk leads to a triage by risk process, wherein the clinician may opt to prescribe opioids, not prescribe opioids, or initiate opioids with risk-mitigation strategies and monitoring of drug-related behaviors . HesitanStigma has been extensively studied and theorized following the publication of Goffman’s seminal text , which dIn relation to opioids, it has been argued that the stigmatized history of opioids has defined the current epidemic, rather than arising as a parallel process in response to the crisis . RegardlOver the past 20 years, news media coverage on the opioid epidemic and prescription opioids has dramatically increased, with more than 35,000 online news reports from 2018 to 2019 in the United States alone . News stThe WHO identifies pharmacovigilance as aiming “to enhance patient care and patient safety in relation to the use of medicines, and to support public health programs by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines” . This coHealthcare professionals often have very differing views on the role of opioids in cancer pain management, which may be related to their discipline and the type of care they provide . For exaThere are several studies which evaluate the diverse physician perceptions of opioid use in the context of cancer pain management. In a survey of more than 600 U.S. medical oncologists, a majority of respondents described themselves as less conservative in prescribing opioids than their peers and reported physician reluctance in opioid prescribing as a barrier to optimal pain management . DespiteWhile the adverse effects of the opioid epidemic are most prevalent in North America , manifesDimensions of opioid stigma expressed by healthcare professionals are further affected by patient demographics, which may result in differential pain management that is prejudiced against minority or disadvantaged groups. Studies suggest that healthcare providers’ distinction between patients who have legitimate or illegitimate pain tends to be influenced by class and racial characteristics ,95, simiIn addition to evidence related to physician accounts, patients with advanced cancer report that their opioid use is stigmatized by healthcare providers, particularly those outside the oncology setting . PatientPoor opioid adherence has been reported among patients with cancer, and research has found consistent underutilization of opioids by patients with cancer pain ,106. A sFear is one of the most commonly reported feelings relating to opioid use among patients with advanced cancer, and may arise from concerns regarding addiction, dependence, diminishing opioid efficacy, and side effects ,111,112.Beyond fears regarding the risk of opioid use, patients often feel shame or guilt, which are constructs of the stigma surrounding opioid use. While it may be viewed as rational that patients have concerns about opioid dependency or side effects, feelings of shame and guilt, especially among patients who are following medical instruction and gaining clinical benefit from opioids, are largely detrimental. Even when partaking in opioid-restricting behaviors, patients express feeling morally compromised and experiencing guilt relating to substance use . It was A final major theme identified from studies investigating self-stigma among patients with advanced cancer is discomfort with sharing concerns with providers, and feelings that they will be perceived as a “pill-seeker” . PatientAttempts to destigmatize patient perceptions of opioids can remove a barrier from the effective management of pain and allow patients to feel more comfortable with adequately managing their pain. While there is a growing interest in investigating the manifestations of opioid stigma in this population, there is a general lack of evidence on how these issues may be combatted. Additionally, the majority of research on patient experiences of opioid stigma has been conducted in the United States, and more research would be useful to better understand global patient experiences.Further education on these topics is needed among clinicians who, as a result, may be better able to communicate with patients in a destigmatizing manner. A conceptual framework for opioid stigma has been developed for the context of cancer pain  and may In other stigmatized domains, such as mental health, tailored multilevel interventions to educate and communicate about stigma have been found to be beneficial in alleviating negative perceptions . StudiesIn addition to interventions directly targeting the foundations and consequences of opioid stigma, the effective treatment of cancer-related pain requires involvement of a multidisciplinary team . It has There is a need for personalized pain management strategies among patients with cancer, for whom both their pain and ability to manage it are modulated by individual factors such as mood, beliefs, culture, and pain etiology. Guidelines have been developed which encourage open conversations about patient goals and concerns regarding pain management which can facilitate personalized treatment decisions with the help of a multidisciplinary team . HoweverAdditionally, the use of multimodal pain management strategies may aid in addressing pain undertreatment and the outcomes resulting from opioid stigma. The use of atypical opioid analgesics  or furthOpioids are an essential therapeutic option for symptom and pain management among patients with advanced cancer. However, the opioid crisis has led to highly publicized and widespread stigmatization of opioid use, which affects both patients and providers. While responses to the opioid crisis were not intended to affect the cancer population, stigma has transcended the intended scope of guidelines and become a significant barrier to pain management for patients with advanced cancer. Stigmatization manifests among healthcare professionals who provide access to opioids, and can result in disparities in access to resources among minorities or groups with increased stigma.In spite of healthcare professionals being the gatekeepers of opioid analgesics, the most significant barriers to cancer pain management relate to the self-stigma experienced by patients. Patients with advanced cancer have fears related to addiction and diminishing returns, shame regarding their need for opioids, and difficulties communicating with providers about these topics. Self-stigma can act as a barrier to pain reporting, which makes physicians’ pain assessment impossible. This stigma may also act as a barrier to prescription adherence, which means that, even in the case of perfect prescribing practices, patients may not experience freedom from their pain.Healthcare professionals should therefore be prepared to initiate and maintain conversations with patients such that stigma is reduced, not amplified or ignored. Specific and standardized risk assessment tools should take into account opioid stigma in order address imbalanced pharmacovigilance. Furthermore, accurate risk assessment for the advanced cancer population cannot be accomplished without a better understanding of the real-world risks of opioid use, which would allow for a well-informed benefit-to-harm framework for decision-making. More research is needed, not only to understand the experience of opioid stigma by these patients, but to provide complete information to patients, which demonstrates that they do not need to be afraid, shameful, and living with uncontrolled pain.


Conclusions: Kinesio taping in addition to NSAIDs was found to be more effective than NSAIDs alone in increasing the degree of jaw opening, decreasing pain intensity, and reducing the non-steroid anti-inflammatory dosage in patients after impacted mandibular wisdom teeth surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly administered according to protocol for the management of complications such as pain, swelling, and trismus following the removal of the third impacted lower molar; however, treatment with NSAIDs may result in multiple adverse effects. The aim of this study was to compare the effectiveness of kinesio taping (KT) and the use of NSAIDs in the treatment of postoperative complications after extraction of an impacted third lower molar. Material and methods: The study comprised a group of 30 patients, randomly divided into the test group  or the control group . The surgery was performed according to standard procedures. In the test group, KT was applied immediately after surgery. Pain, swelling, and trismus were assessed. The VAS scale was used to assess pain. Swelling was measured based on six reference points on the face using a tailor’s meter, and a caliper was used to measure the distance between the upper and lower medial incisors of the upper and lower teeth to determine the extent of trismus. Measurements were performed three times: on the day of the surgery, on the second day following the surgery, and on the 7th day after the surgery. Results: Pain intensity (day of procedures), maximum mouth opening (on the seventh day after the surgery), and the use of NSAIDs (day of surgery) were significantly lower ( Cannabis sativa L. represents an interesting source of bioactive compounds, including non-psychoactive cannabinoids, flavonoids, and terpenes, many of which are effective in reducing pain intensity [Surgical removal of the impacted mandibular third molars is a dental procedure performed by dental surgeons. However, it bears a high risk of postoperative complications such as pain, swelling, and trismus; thus, all contraindications and possible postoperative complications should be analyzed . Moreoventensity . Persistntensity .Another example of an alternative method of orofacial pain relief is the use of kinesio taping. The application of tapes does not limit the range of mobility and therefore does not impact daily routines. The tape works upon the skin-fascia correlation, facilitating mutual displacement of the tissues, while facilitating subcutaneous flow and eliminating stagnation as well as lymphatic edema . Kinesio taping (KT) is a non-invasive method developed in Japan to support both treatment and rehabilitation ,7. It haTapes gently lift the skin and decompress underlying soft tissues through the formation of convolutions; thus, the circulation in subcutaneous space is improved. Moreover, stimulation of skin mechanoreceptors blocks the signal due to gate control theory, resulting in pain alleviation ,11. KineA randomized study was conducted to compare the effect of the application of kinesio taping vs. no taping on patients after the extraction of the lower third molar.Power analysisA sample size was estimated for the main outcome measure, the change in MMO , considering the results of the study by Tatli et al.  . RANDOM.ORG: True Random Number Service ).Even-numbered patients were assigned to the test group , and those with an odd number were assigned to the control group  .The research took place between November 2020 and June 2021 in the Department of Oral Surgery at the Medical University of Silesia in Katowice, Bytom, Poland.The study was approved by the Bioethical Committee of the Medical University of Silesia in Katowice (Resolution no. PCN/022/KB1/56/20).Consecutive patients were selected based on the following criteria : patientIn each participant the lower third molar was extracted and the level of swelling, degree of jaw opening, and pain were measured. In the test group, kinesio taping was applied .The surgical procedures to extract the lower third molar were carried out in patients of both groups by the same operator, using a repeatable technique.Infiltration and conduction anesthesia were administered to the mandibular foramen with two ampoules of Lignocainum hydrochloricum 2% cum noradrenalin 0.00125% , then the mucoperiosteal flap was dissected from an angular incision. A small amount of bone was removed from the outside with a drill. The exposed tooth was either removed completely after separation of the crown from the roots. The bone bed was cured, and in case of any pathological changes, the specimen was sent for histopathological examination. The post-extraction wound was sutured using non-absorbable nylon surgical sutures—Braun Dafilon—USP 4/0, DS. 24.75 cm, 3/8 circle , and a pressure dressing was applied for approximately 30 min. Each surgical procedure to remove the third lower molar was preceded by measurements taken in the clinical room. A cephalostat was used to obtain the repeatable position of the head, adjusted and recorded individually for each patient, followed by metric measurement of the facial integuments in relation to specific reference points and measurement of the degree of mouth opening. The patient’s head was stabilized for repeated measurements .A tailor’s meter was used to determine the degree of swelling based on the measurable parameters . Five diIn order to determine the occurrence of trismus, a caliper was used to measure the distance (mm) between the upper and lower medial incisors of the upper and lower teeth. Measurements were taken before the procedure and during follow-up at two and seven days after the procedure.The VAS scale was used to record the subjective pain sensations of patients in both groups. The VAS scale is a visual analogue scale that measures pain intensity. It consists of a 10 cm line with two end points that represent 0 (‘no pain’) and 10 (‘pain as bad as it could possibly be’) . The resAll of the procedures carried out within the study to evaluate the effectiveness of kinesio taping after extraction of the third lower molar were carried out by the same physiotherapist with the use of Kinesio Tex Classic tape . The length of the tape was measured individually for each patient, starting from the subclavian fossa and ending at the zygomatic arch. The tape was cut into five equal strips of 1 cm in width each to form the shape of a fan. Before sticking the tape, the patient’s skin was cleaned, degreased, and dried . The KT tape was placed to form a single fan over the area of expected edema . The skiBoth Groups were instructed to take 100 mg of Ketoprofenum—Ketonal Forte in case of pain as needed.p < 0.05.Statistical analyses were performed using the Python 3.7  and SciPy 1.4.1  and Kruskal–Wallis one-way ANOVA tests were used to evaluate differences among the groups at the same time interval. The level of significance was The mean age of participants in the test group was 22.93, and in the control group it was 29.73. There were nine women and six men in the test group, and twelve women and three men in the control group .p = 0.128). On the second and seventh days after surgery, the ratio of maximal mouth opening compared to the original maximal mouth opening was calculated, and we found that on the second day, the difference between the groups was not statistically significant (p = 0.073). On day 7, the difference between the groups was statistically significant (p = 0.0101). KT values were higher than those in the control group during both follow-up visits , with a significant decrease in pain in both groups when compared to their respective baseline measures. On days 2 and 7, the differences between the groups were not statistically significant   .p = 0.765). On the second and seventh postoperative days, the ratio of the sum of all the lines drawn to the sum of the baseline face measurements was calculated, which revealed no significant differences between the groups   .p = 0.0102 and p = 0.0131, respectively). On the seventh postoperative day there was no statically significant difference .The aim of our study was to compare the effectiveness of kinesio taping (KT) in combination with NSAIDs with the use of NSAIDs alone in the treatment of postoperative complications after extraction of the impacted third lower molar. Analysis of the results showed a significant difference in mouth opening seven days after surgery  in the test group one day after surgery. The measurement of pain assessed by the patients on the VAS scale and the amount of analgesics taken were statistically significant in our study. The VAS scale is an internationally recognized tool that allows the patient to easily assess their pain. The results of our study showed that the average pain complaints assessed by the patients on the VAS scale were significantly lower in the test group (p = 0.0114) compared to the control group, one day after surgery. Moreover, patients from the test group reported a significantly lower intake of NSAIDs one day after surgery (p = 0.0102) and two days after surgery (p = 0.0131) when compared to a control group.Post-extraction pain reduces the patients’ quality of life, and it is an indication for taking analgesics, especially NSAIDs. There is a great need to introduce pain-reducing treatment, especially using methods without side effects. Kinesio taping is one such treatment. The results of our study showed that the average pain complaints assessed by the patients on the VAS scale were significantly lower (In our study, no significant difference was observed between the control and test groups with regard to facial tissue swelling.The measurement of edema was not markedly higher in the study group than in the control group. Kasprzyk-Kucewicz et al. proved in their study that thermal imaging can be helpful in the assessment of the postoperative condition in dental surgery, and its usage may be considered in studies examining the effectiveness of kinesio taping .In 2019, Tristão da Rocha Heras et al. observed a small group of patients showing a positive effect of KT on reducing the side effects of surgical extraction of the impacted wisdom teeth . This enIn the study above, patients who underwent surgical removal of the third molar were evaluated during the postoperative period. Four parameters were assessed: trismus, measured by the maximum opening of the mouth; swelling; pain intensity on the VAS scale; and the amount of analgesics taken by the patients throughout the postoperative period. The parameters were assessed equally in both the control and the test groups.In their study, Ristow et al.  did not In his studies on the use of KT in patients after orthognathic surgery and repositioning of orbital-zygomatic fractures ,33, the Analyzing the subsequent study by Tristão da Rocha Heras et al. evaluating the use of KT in patients after surgical extraction of the third molar , attentiTaking into consideration the respondents’ comfort, our study made it possible to take NSAIDs in the event of pain, while the patients were requested to assess their pain with the use of the VAS scale before medication. This ensured the assessment of this parameter and, at the same time, the observation of the amount and changes in the demand for analgesics in each of the patients. The authors of the recent study did not decide to administer dexamethasone, as performed by Tristão da Rocha Heras and colleagues.Jaroń et al. in their study from 2021 measured three parameters: trismus, swelling, and pain in two groups who underwent surgical removal of an impacted third lower molar. Both groups used the same pharmacological postoperative protocol. The patients were instructed to use ketoprofen in a 100 mg dose taken twice daily. The patients in the study group had the kinesio tape applied immediately after the surgery. The 50 mm-wide tape was cut into three separate pieces of equal width. The study showed a significant decrease in trismus and pain sensation on the third and seventh days after surgery and a significant decrease in facial swelling on the third day after surgery .Al-Shamiri et al. studied the effectiveness of dexamethasone, emphasizing the beneficial effect of preoperative or postoperative oral administration of dexamethasone in the management of postoperative complications following lower third molar surgeries, including pain, swelling, and trismus. It may be concluded that oral application of dexamethasone before the surgery substantially reduces pain sensation .Yurttutan and Sancak  also anaIn their study, Gözlüklü, Ulu, and Yilmaz  comparedInterestingly, the results showed that the new taping technique provided more effective pain relief than the standard one. The swelling assessment using the face system can also be more effective than the classic method used in previous studies.Of note is the latest study by Tatli et al.  investigThere is no consensus among the researchers regarding the duration of kinesio taping. Genc and Erdil kept tapes for two days ,39; JaroAt present, three meta-analyses have been published, however the results are ambiguous. A paper by Firozi et al.  where heWang, Zhu, Guo, and Sun  conducteQi et al.  comparedAfter offering postoperative kinesio taping care to a wide group of patients, only a small portion of them agreed to participate in our study, which we believe is due to the low level of knowledge about kinesio taping in our region. With our research, we want to popularize kiensio taping among patients in the region of Silesia, which in the future will allow us to gather a larger research group.In summary, kinesio taping is a relatively low-cost and simple procedure, reducing the use of drugs and showing encouraging prospects for the postoperative care after extraction of impacted mandibular third molars.Our findings should be interpreted with caution due to the small sample size and the unequal number of men and women. Poor knowledge about kinesio taping limits the number of patients included in the study; however, this research is being continued on a larger scale with a larger sample size.Kinesio taping in addition to NSAIDs was found to be more effective than NSAIDs alone in increasing the degree of jaw opening, decreasing pain intensity, and reducing the dosage of non-steroidal anti-inflammatory drugs in patients after impacted mandibular wisdom teeth surgery. The cooperation of dental surgeons and the physiotherapeutic team is associated with a measurable benefit, which is the reduction of the inflammatory process and a significant reduction in the use of non-steroidal anti-inflammatory drugs. It should be introduced as a standard in the surgery of impacted lower molars.


N = 68, accuracy = 68.8%, p = .001). Linear regression and random forest could also distinguish cLBP and HCs in the independent cohort . Overall, these findings provide evidence that cLBP may be associated with abnormal rsFC and effective connectivity of the habenula, and highlight the promise of machine learning in chronic pain discrimination.The habenula has been implicated in the pathogenesis of pain and analgesia, while evidence concerning its function in chronic low back pain (cLBP) is sparse. This study aims to investigate the resting‐state functional connectivity (rsFC) and effective connectivity of the habenula in 52 patients with cLBP and 52 healthy controls (HCs) and assess the feasibility of distinguishing cLBP from HCs based on connectivity by machine learning methods. Our results indicated significantly enhanced rsFC of the habenula‐left superior frontal cortex (SFC), habenula‐right thalamus, and habenula‐bilateral insular pathways as well as decreased rsFC of the habenula‐pons pathway in cLBP patients compared to HCs. Dynamic causal modelling revealed significantly enhanced effective connectivity from the right thalamus to right habenula in cLBP patients compared with HCs. RsFC of the habenula‐SFC was positively correlated with pain intensities and Hamilton Depression scores in the cLBP group. RsFC of the habenula‐right insula was negatively correlated with pain duration in the cLBP group. Additionally, the combination of the rsFC of the habenula‐SFC, habenula‐thalamus, and habenula‐pons pathways could reliably distinguish cLBP patients from HCs with an accuracy of 75.9% by support vector machine, which was validated in an independent cohort ( Our study revealed abnormal resting‐state functional connectivity and effective connectivity of the habenula with cortical/subcortical areas in patients with chronic low back pain than healthy control subjects, and the habenula connectivity can be used to distinguish chronic low back pain and healthy controls reliably by machine learning methods. Fifty‐two HCs  were recruited via advertisement. The study was approved by the Research Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (number 2015049). The diagnosis of cLBP was performed by two experienced clinicians (Q. J. and S. QC). The HCs were recruited from the surrounding area through advertisements and word‐of‐mouth. The HCs were required to have no history of any pain or neurological disorders and met the following exclusion criteria. All participants provided written informed consent prior to entering the study. The medications for all cLBP patients can be found in the Supplemental materials.2.1.1Participants were considered to be in the cLBP group if they (1) met the criteria of the International Association for the Study of Pain for the diagnosis of cLBP  had concomitant psychiatric disorders, substance abuse/dependence, treatment with antidepressants or other medications that would affect the study results; (2) had a history of significant head trauma; (3) had chronic pain in other body sites; or (4) had contraindications to MR imaging .2.1.3The short‐form McGill Pain Questionnaire Melzack,  was used2.23, field of view: 256 mm × 256 mm, 150 slices. The resting‐state blood oxygen level‐dependent (BOLD) data were obtained using a gradient echo‐planar MR imaging sequence with the following parameters: TR: 2500 ms, TE: 30 ms, flip angle: 90°, slice thickness = 3 mm, zero gap, voxel size: 4 × 4 × 3 mm3, field of view: 256 mm × 256 mm, 50 slices, 158 volumes, lasting for 6 min 35 s.MRI data were acquired on a 3.0‐T whole‐body MR scanner  equipped with a standard eight‐channel head coil. All participants were required to abstain from medications for 12 h before the MR scan. High‐resolution anatomic T1‐weighted images were acquired using a 3D‐T1‐weighted fast spoiled gradient echo sequence with the following parameters: time to repetition (TR): 10.8 ms, time to echo (TE): 4.8 ms, flip angle: 15°, slice thickness = 1 mm, space between slices = 0, voxel size: 1 × 1 × 1 mm2.32.3.1https://www.nitrc.org/projects/artifact_detect), and functional smoothing . A combination of aComCor , scrubbing, motion regression , and filtering were used to reduce the noise (band: 0.008–0.09 Hz). The “outliers” refer to the regressors used in the scrubbing regression, that is, the images whose composite movement from a preceding image exceeded 0.5 mm, or if the global mean intensity was >3 standard deviations from the mean image intensity of the entire resting scan. Moreover, we also included the maximum interscan movement (framewise displacement)  corrected for the between‐group comparisons.Seed‐based rsFC analysis was performed in the CONN toolbox. The seeds for the left and right habenula proposed by Kim et al.  were com2.3.3x = −14, y = −24, z = 2; right: x = 14, y = −24, z = 2; Figure In addition to the habenula seed, we created a control seed containing spherical ROIs of bilateral thalamus ; right thalamus ; left habenula ; right habenula ; and pons . In square brackets, there are corresponding MNI coordinates of the centres of regions. The time series were extracted from the upper ROIs based on the preprocessed but unsmoothed data from CONN analyses. Seven models were specified, including a fully connected model, three models excluding one of the three regions including the SFC, thalamus, or pons, and three models excluding any two of the upper three regions. Fixed effects Bayesian model selection (BMS)  .Finally, to assess whether different connectivity methods  reflect similar neural interactions in the same subjects, we explored the relationship between the rsFC and effective connectivity of the habenula by Spearman rank correlation analysis as reported in previous studies .To validate the results from the CONN and DCM analyses, we repeated these two analyses in an independent cohort including 34 cLBP patients and 34 HCs. The MRI data were obtained from the OpenPain Project database (2.5Support vector machine (SVM) learning was used to classify cLBP subjects and HCs implemented on the LIBSVM toolbox version 3.18 in MATLAB R2021a  in the cLBP group.SPSS 24.0  was used to perform the statistical analyses that were not included in the CONN and DCM analyses. Age and HAMD scores were compared by independent sample 2.7Habenula is a small structure. In order to keep the spatial accuracy and avoid the effect of neighbouring nuclei on results of the habenular rsFC as suggested in previous study . Detailed demographic and clinical characteristics are shown in Table There were no significant differences in age or gender between cLBP patients and HCs. The depression scores were significantly higher in cLBP patients than in HCs p < .00. Detaile3.2p = .013, FDR corrected), right thalamus , and bilateral insular cortex  as well as cingulate cortex . In addition, patients with cLBP showed significantly enhanced rsFC between thalamus and left posterior insular cortex . The results can be seen in Supplemental Materials  compared with HCs , right thalamus , and left temporal cortex  in patients with cLBP compared to HCs after controlling for the effects of age, gender, and depression scores  and HAMD scores  in patients with cLBP. The rsFC of the habenula‐right insula was negatively correlated with pain duration  in patients with cLBP. There were no significant correlations between habenular effective connectivity and pain characteristics/depression scores. Association analysis of habenular rsFC and effective connectivity suggested no significant correlations in patients with cLBP.The habenula‐SFC rsFC values were positively correlated with VAS  showed significantly decreased rsFC of the habenula‐pons pathway, and enhanced rsFC of the habenula‐left SFC/right thalamus pathways as compared with HCs (52 subjects). For the second dataset, patients with cLBP (34 subjects) showed significantly enhanced rsFC of the habenula‐left SFC/right thalamus pathways, and decreased rsFC of the habenula‐periaqueductal grey (PAG) pathway as compared with HCs (34 subjects). The results are shown in the Supplemental Materials Table .4Here, we compared the rsFC and effective connectivity of the habenula between cLBP patients and HCs and used these features to distinguish cLBP patients from HCs by machine learning methods. We found significantly different habenular connectivity patterns associated with pain intensities and/or depression states in patients with cLBP and HCs. SVM learning, linear regression, and random forest could reliably distinguish cLBP from HCs based on habenular rsFC.CLBP is a multi‐dimensional experience including physiological, affective, cognitive, behavioural, and social components  pathways was also suggested in patients with cLBP compared with HCs. The rsFC of the habenula‐right insula was negatively associated with pain duration and HAMD scores. Thalamo–habenula connectivity has been thoroughly examined in various vertebrates but is not well defined in humans  by ultrafield MR or more precise segmentation techniques might help to clarify the structural changes of the habenula in patients with cLBP . OPP funding was provided by the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Drug Abuse (NIDA). OPP data are disseminated by the Apkarian Lab, Physiology Department at the Northwestern University, Chicago.FIGURE S1 Spherical regions of interest in bilateral thalamus.FIGURE S2 Between‐group comparisons of the thalamus‐cortical functional connectivity between 52 healthy controls and 52 patients with chronic low back pain.TABLE S1 Group differences of the resting‐state functional connectivity of the thalamus between 52 healthy controls and 52 patients with chronic low back pain.TABLE S2 Demographical and clinical data of the independent cohort.TABLE S3 Group differences of the resting‐state functional connectivity of the habenula in the independent cohort.TABLE S4 Mean connection strengths (in Hz) of 34 healthy controls and 34 patients with chronic low back pain in the independent cohort.TABLE S5 Classification performance of the three classifiersTABLE S6 Group differences in the resting‐state functional connectivity of the habenula with unsmoothed data between 52 cLBP patients and 52 healthy controlsTABLE S7 Group differences in the resting‐state functional connectivity of the habenula between 34 cLBP patients and 32 healthy controls.Click here for additional data file.


Background: Anesthetic technique and postoperative pain management are crucial for total joint arthroplasty (TJA) patients. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) are new, simple, and cost-effective predictors for prognosis. The predictive value of NLR as an inflammatory marker can predict post-operative pain caused by inflammatory pathways secondary to surgical trauma. CRP is also the most sensitive and specific biomarker of inflammation whereas PLR was also recently considered a possible marker for inflammation which may further contribute to pain and sequelae. Thus, anesthetists can make decisions about the amount, time, and type of analgesic to use based on preoperative values of these parameters to provide maximum postoperative pain control and facilitate early rehabilitation. Thus, the current study was conducted to determine the relationship between CRP, NLR, and PLR levels and the intensity of pain in patients following total hip arthroplasty (THA) and total knee arthroplasty (TKA).Materials and Methods: A total of 105 patients scheduled for THA and TKA fulfilling the study's inclusion criteria were enrolled. Inclusion criteria of the study were all the patients giving written consent, ASA Grade I-III, patients between 18 and 90 years who were scheduled for elective lower extremity TJA, and all the patients who remained admitted until stitches were removed. Patients were given intrathecal 15 mg hyperbaric bupivacaine via 25G atraumatic spinal needle in the L3-L4 interspace. The recorded data were demographic characteristics, preexisting comorbidities, number of blood transfusions, and operation time, postoperative analgesics given, duration of hospital stay, time of mobility, pain scoring as per visual analog scale (VAS) scoring system with an aim to establish a relationship between pre- and post-operative (Days 3 & 5) CRP, NLR, and PLR with post-operative pain after THA and TKA.Result: The present study demonstrated a significant correlation (p < 0.002) between preoperative and postoperative NLR with pain after TJA whereas PLR and CRP did not show any significant relationship with post-operative pain after THA and TKA. A significantly higher NLR ratio was observed for patients on all the periods of observation . Pre-op. and Day 5 NLR of patients who required transfusion were significantly higher than those who did not require transfusion and patients with higher NLR values could be mobilized significantly later and had significantly higher duration of hospital stay. The correlation of CRP levels and PLR levels at different time intervals did not show a significant correlation with Day 3 and Day 5 pain scores.Conclusion: The present study demonstrated a significant correlation between preoperative and postoperative NLR with pain after TJA. Osteoarthritis (OA) is one of the most prevalent chronic degenerative diseases of the middle-aged and elderly. Worldwide, it is believed that between 10% and 15% of persons over the age of 60 suffer from OA. Around the world, roughly 86.7 million people are anticipated to have symptomatic knee OA, according to the 2020 report [Although TJA helps to reduce pain in the majority of patients, a variety of postoperative complications may result in adverse outcomes, including periprosthetic joint infection (PJI), one of the most serious complications of TJA, which occurs in approximately 1%-3% of all TKAs, and moderate to severe persistent postoperative pain (PPP) in the operated knee three months after surgery, which is experienced by approximately 1%-3% of all TKAs [The C-reactive protein (CRP) levels revert to preoperative levels within three weeks; however, they may be raised for a variety of reasons in addition to postoperative infection, given the high prevalence of TJA in elderly patients with concomitant diseases . RecentlAccording to Forget et al., the normal NLR value in healthy people should be 1.65, but within a larger range of 0.78-3.53. However, the average NLR value has been found to be greater (2.15), and it varies with race -11. The Platelets activated in response to the rupture of atherosclerotic plaques or endothelial cell erosion promote the production of thrombus, hence promoting atherothrombotic disease . PLR wasDetermining the level of CRP in the postoperative period following TJA can be used to measure the pain syndrome, allowing for an objective assessment and adjustment of the anesthetic strategy used. The NLR and PLR are simple and inexpensive biomarkers for systemic inflammation. To provide maximum post-operative pain control and to facilitate early rehabilitation in THR and TKR patients, a screening test to rule out the risk of infection is critical. Thus, the current study was conducted to determine the relationship between CRP, NLR, and PLR levels and the intensity of pain in patients following TKA and THA.After getting clearance from the ethical committee, the study was conducted in the Department of Anesthesiology and Critical Care, King George’s Medical University with CTRI/2021/02/031240. This prospective, observational, cohort study was conducted for one year to correlate post-operative pain of patients of THA and TKA with pre- and post-operative CRP, NLR, and PLR. A total of 105 patients scheduled for THA and TKA fulfilling the inclusion criteria of the study were enrolled in the study after obtaining informed consent. Inclusion criteria of the study were all the patients giving written consent, ASA Grade I-III, patients between 18 and 90 years who were scheduled for elective lower extremity TJA, and all the patients who remained admitted until stitches were removed. Exclusion criteria were the patients having complications of pneumonia, wound infection, urinary tract infection, malignancy, chronic inflammatory disease history, or corticosteroid use and emergency operations.The sample size was calculated by taking the maximum area under the curve (AUC) of the parameter among all the parameters under study using the formula :Where,p = 0.155 (15.5%), prevalence of disease as found in the study e = 0.25, error factor for detecting results with 90% power of study Type I error (level of significance) α=0.05Data loss factor = 10%Then, the minimum sample size required would be n = 105.ProcedurePatients were given intrathecal 15 mg hyperbaric bupivacaine via 25G atraumatic spinal needle in the L3-L4 interspace in a sitting position. Preoperative periarticular or intraarticular injections were not given. Patients were mobilized and a standardized rehabilitation protocol was started on the first day after surgery in both groups. Patients with preoperative CRP levels > 10 mg/L were also excluded, as well as any other inflammatory or medical complication during the hospital stay.All patients received the same prophylactic antibiotics (1 g of ceftriaxone) within 1 h before incision. IV antibiotics were administered to all patients for 2 days. Tolerable weight-bearing ambulation was allowed on the second postoperative day after drain removal. Rescue analgesics were given in form of IV Tramadol and transdermal patches (buprenorphine and fentanyl patches). The recorded data were demographic characteristics, preexisting comorbidities, number of blood transfusions, operation time, postoperative analgesics given, duration of hospital stay, and pain scoring as per the VAS scoring system.We routinely evaluated preoperative white blood corpuscles (%), CRP, and platelet count. Venous blood samples of all patients were obtained preoperative 24 h before surgery, postoperative on Day 3 and Day 5. The VAS scores were noted on Day 3 and Day 5 and were denoted from a scale of 0-10 where scores 1-3 = low pain, 4-6 = moderate pain, and a score of >6 = high pain. We also noted the day of mobilization, duration of hospital stay, and post-operative complications.Statistical analysisThe statistical analysis was done using Statistical Package for Social Sciences (SPSS) Version 21.0 Statistical Analysis Software . The values were represented in number (%) and mean ± standard deviation (SD). Student’s t-test, Pearson’s correlation, Spearman’s correlation, and analysis of variance (ANOVA) were applied for data analysis as applicable. A p-value < 0.05 was considered statistically significant.Table Table The mean VAS score for pain on Day 3 was 4.30 ± 1.32 (Range 1-6), two thirds of patients had moderate pain (score 4-6). On Day 5 mean pain score was 3.30 ± 0.96 (Range 2-6); the majority of patients had a low level of pain (score 1-3). A statistically significant decline in Day 3 pain was observed on Day 5 (0.99 ± 1.24). The percentage decline in pain on Day 5 was 23.0%. A significant correlation (p<0.002) between pain at Day 3 and Day 5 was found, and the level of correlation was found to be mild (r=0.449)  with a higher level of Day 3 pain (moderate level) as compared to a lower level of pain (low pain) Table .A higher NLR ratio was observed for patients on all the periods of observation  with a higher level of Day 5 pain (moderate level) as compared to a lower level of pain (low pain). Pre-operative NLR of patients with low and moderate pain were found to be comparable Table .Significant correlations between Day 3 and Day 5 pain were observed with pre-op., Day 3, and Day 5 NLR Table .Pre-operative and Day 3 PLR of patients with low Day 3 pain and moderate pain were comparable. The Day 5 PLR of patients with moderate Day 3 pain was significantly higher as compared to those with low Day 3 pain Table .Pre-operative and Day 5 PLR of patients with low Day 5 pain and moderate pain were comparable. Day 3 PLR of patients with low Day 3 pain was significantly higher as compared to those with moderate Day 3 pain Table .Pre-op., Day 3, and Day 5 PLR did not show any significant correlation with post-operative pain at different time intervals Table .Patients with Day 3 moderate pain as compared to those with low pain could be mobilized significantly later (2.40 ± 0.49 vs. 2.03 ± 0.17 days) and had a significantly higher duration of hospital stay (11.83 ± 2.01 vs. 10.00 ± 0.00 days) Table .Patients with Day 5 moderate pain as compared to those with low pain could be mobilized significantly later (2.43 ± 0.50 vs. 2.15 ± 0.36 days) and had a significantly higher duration of hospital stay (11.83 ± 2.01 vs. 10.75 ± 1.57 days) Table .Table Table On all the periods of observation, patients with a history of myocardial infarction and a history of TIA had higher NLR but differences with patients with other comorbidities/no comorbidity were found to be statistically significant only for Pre-op. NLR Table .The present study demonstrated a significant correlation between preoperative and postoperative NLR with pain after TJA. The correlation of CRP levels at different time intervals did not show a significant correlation with Day 3 and Day 5 pain scores. PLR at pre-operative, Day 3, and Day 5 did not show any significant correlation with post-operative pain at different time intervals. Post-operative CRP level is an indicator reflecting the invasiveness of surgical procedures. The elevated CRP levels during the postoperative period are known to be closely associated with postoperative complications including infections. Godoy et al.  concludeAdequate management of postoperative pain results in increased patient comfort and decreased mobilization time, systemic complications, and recovery period without disturbing memories related to surgery. Inflammation triggered by surgical trauma secondary to incision, dissection, suturing, nerve stretching, or nerve compression takes part in the mechanism of postoperative pain. Hernández et al.  concludeCanbolat et al.  concludeThe platelet-to-lymphocyte ratio (PLR) has emerged as an informative marker revealing shifts in platelet and lymphocyte counts due to acute inflammatory and prothrombotic states. Yao et al.  concludeGorial et al.  concludeIn our study, it was observed that patients with day 3 moderate pain as compared to those with low pain could be mobilized significantly later (2.40 ± 0.49 vs. 2.03 ± 0.17 days) and had a significantly higher duration of hospital stay (11.83 ± 2.01 vs. 10.00 ± 0.00 days) and patients with day 5 moderate pain as compared to those with low pain could be mobilized significantly later (2.43 ± 0.50 vs. 2.15 ± 0.36 days) and had a significantly higher duration of hospital stay (11.83 ± 2.01 vs. 10.75 ± 1.57 days).The present study has the following limitations. The study is an observational cohort study, and may not necessarily reflect the real-world association of the studied biomarkers.Substantial heterogenicity of our study population  might have confounded our results as the immune response to surgical stress is different in different age groups. Spinal anesthesia alone was not adequate to provide surgical anesthesia to patients with intraoperative difficulties. Laboratory blood tests were not performed in the same laboratory, so the results may not be equivocal. Communication with older patients was difficult; therefore, VAS scores may not have exactly reflected the pain.RecommendationsMulticenter studies in different ages, diseases, and anesthesia specifics should be conducted to validate the result. There should be long-term follow-up for the study. Laboratory tests should be conducted in one laboratory.The present study demonstrated a significant correlation between preoperative and postoperative NLR with pain after TJA. The correlation of CRP levels at different time intervals did not show a significant correlation with Day 3 and Day 5 pain scores. PLR at Pre-op., Day 3, and Day 5 did not show any significant correlation with post-operative pain at different time intervals. Post-operative pain is a significant component of the systemic stress response induced by surgical intervention. Integrating the NLR into clinical practice seems beneficial because it is easy, cheap, and convenient and can be calculated in daily practice without extra cost. In patients with age >60 years, history of myocardial infarction, TIA and anemia, the high NLR on admission can be a predictor of poorer postoperative outcomes including high inflammatory response/infection. This simple and inexpensive biomarker could be used for risk stratification and individualized perioperative pain management. Anesthetists can make decisions about the time and type of analgesic to be used based on NLR values. NLR can be used especially in geriatric patients who might have various central nervous system disorders like Alzheimer’s disease, dementia, age-related cerebral atrophy, Parkinsonism, etc. where expression of pain may be difficult, hence NLR can be used to provide maximum postoperative pain control and to facilitate early rehabilitation and prevention of postoperative complications.