Controversies regarding venous compression and trigeminal neuralgia (TN) still exist. The study demonstrates our experience for microvascular decompression (MVD) in TN caused by purely venous compression. The goal was to identify prognostic anatomical or surgical factors that may influence the outcome.Between 2004 and 2020, 49 patients were operated with purely venous compression. Average age was 58.4 years. Mean history of TN was 7.8 years. Microsurgical procedures included transposition or separation of the vein, coagulation, and division. Several features have been analyzed with respect to BNI scores.p < 0.05).Evaluation on discharge revealed a complete pain relief in 39 (80%), partial improvement in 7 (14%), and no benefit in 3 (6%) patients. Facial hypesthesia was reported by 14 (28.6%) patients. Mean follow-up (FU) was 42.1 months. BNI pain intensity score on FU revealed 71.4% excellent to very good scores (score 1: 32 (65.3%); 2: 3 (6.1%)). BNI facial numbness score 2 could be detected in 13 patients (26.5%) during FU. There was no statistical relationship between immediate pain improvement or BNI pain intensity score on FU with respect to surgical procedure, size of trigeminal cistern, type of venous compression, venous caliber, trigeminal nerve indentation, or neurovascular adherence. BNI facial numbness score was dependent on type of venous compression  nor sacrificing the offending vein made any difference in outcome. Vascular compression of the trigeminal nerve root by an arterial loop at the root entry zone (TREZ) as the main cause of trigeminal neuralgia (TN) is most frequent. But a neurovascular conflict between the trigeminal nerve and a vein can be an acceptable cause of TN too. Barker et al. reported in 1996 the high number of 151 patients in whom a vein only was expected to be responsible for TN , 19. A cWe demonstrate our experience using the endoscope-assisted technique for MVD in patients with TN caused by purely venous compression. The goal of the study was to answer the question whether there are prognostic anatomical or surgical factors that may influence the outcome for these patients.We reviewed our prospectively maintained data base of 262 patients with TN treated between 2004 and 2020. Only patients with a venous compression were included in the study. Patients with a neurovascular conflict not only related to a vein but also to an artery were excluded. 49 18.7%) patients were identified and verified by operating charts, intraoperative images or videos respectively  and facial electromyography monitoring was obligatory in every patient.Several anatomical features had been documented during surgery. The vein and its relation to the trigeminal nerve was classified according to the representative types of TN by venous compression Table  describeWith respect to our experience according to the adherence of vein and trigeminal nerve, we distinguished two types. Type 1, where an obvious arachnoid layer between nerve and vein appeared to be very thin or was missing. Type 2 describes nice anatomical conditions with a well-defined arachnoid plane between nerve and vein comparable to a typical nerve-artery compression. Finally, it was noticed whether an indentation or groove in the trigeminal nerve was seen.The study was approved by the local ethics board. Informed consent was not obtained from every patient, since all examinations had been on regular basis in the outpatient clinic.Immediate clinical outcome after surgery was evaluated. Therefore, postoperatively evaluation of pain was simply graded into complete pain relief, partial improvement or no pain relief. Hypesthesia or dysesthesia right after surgery was recorded. The latest clinical follow-up included the total evaluation score by the Barrow Neurological Institute (BNI) consisting of pain intensity and facial numbness scores .Early clinical evaluation and follow-up BNI score was statistically analyzed regarding type of decompression, types of venous compression Table , neurovap-values < 0.05 used to define significance.Statistical analysis was conducted with SAS 9.3 . Fisher’s exact test for categorical variables was conducted, with Transposition of the vein with introduction of a small piece of Teflon between nerve and vein was performed in 32, coagulation/division in 17 patients. Medium-sized veins were found in 24 (49%), large veins in 15 (30.6%), and small veins in 10 (20.4%) patients. Neurovascular adherence Type 1 was seen in 30 (61.2%), Type 2 in 19 (38.7%) patients. An indentation of the trigeminal nerve was seen in 7 (14.3%) patients. The types of venous compression described by Inoue et al. [2 (0.75–3.21 cm2) and mean value of the length of the trigeminal nerve of 7.1 mm (3–12). For verification of the data, Pearson’s correlation of the parameters was strongly significant (p < 0.001). With respect to this analysis trigeminal cistern was wide in 27 (> 1.67cm2) and narrow in 22 patients , partial pain improvement in 7 (14%), and no benefit in 3 (6%) patients. One of the patients who did not improve initially, reported pain relief after several months. Facial hypesthesia or paresthesia was reported by 14 (28.6%) patients. None of them reported sensory deficits before surgery. Three of them revealed slight improvement at final FU,11 patients remained unchanged. Whether a change of auditory evoked potentials was observed or not in relation with venous sacrifice could not be analyzed retrospectively.Postoperative complications were seen in 4 patients. There was a transient partial hearing loss and dizziness in one patient each. In another patient, meningitis was diagnosed and treated with antibiotics. One patient developed transient double vision due to a venous congestion with cerebellar edema. In this patient, a compressive petrosal vein was sacrificed. Fortunately, clinical symptoms and edema resolved completely.Mean follow-up (FU) was 42.1 months (range: 3–144 months). Two patients reported a resolution of pain after primary unsatisfactory benefit. Two patients never got any benefit from surgery. After a pain free interval, six patients (12.2%) developed recurrent pain within 4 months up to 7 years.With respect to overall BNI evaluation Table , the BNIWe offered 6 patients with recurrent pain  a re-exploration. All of them were informed about the option of a partial sensory rhizotomy (PSR). Three of them refused this option. In none of the patients, a new neurovascular conflict was found. Three patients received PSR. The Teflon sponge was removed in all patients if feasible (neurolysis). On discharge, patients who received a PSR reported a resolution of pain. The remaining 3 patients reported a slight benefit.There was no statistical relationship between immediate pain improvement and kind of surgical procedure, size of trigeminal cistern, type of venous compression, venous caliber, trigeminal nerve indentation or neurovascular adherence. BNI pain intensity score on FU was analyzed with all aspects. There was no significant relationship.p < 0.05) with respect to the type of venous compression. Type C and D of Inoue et al. [p = 0.74)).There were 14 patients (28.6%) with a BNI facial numbness score of 2 (13 patients) or 3 (1 patient). Statistical analysis revealed a significant value .Additionally, we did a correlation analysis for pain relief and presence vs absence of facial numbness. The Fisher’s exact test for categorical variables was used. We found no correlation between pain relief versus presence or absence of facial numbness  with a facial sensory deficit still present at FU. Only a few studies report an observation of facial numbness of 20.7%, 26.7% or 29% and 22% at FU , 6, 7. D% with a Complete pain relief on FU was achieved for 32 65.3%) patients. Some studies report full pain resolution on FU of 60%, 67%, 69.6%, and 80% respectively 5.3% pati. Out of The main limitations of our study are the small number of patients and the short follow up period. Furthermore, it is a single center evaluation. Venous compression of the trigeminal nerve as a cause of TN is still rare. Factors included in this study, like neurovascular adherence or caliber of the offending veins are based on a subjective evaluation of the authors.Doubtless venous compression of the trigeminal nerve is one of the causes of classic TN. Venous anatomy is very variable and complex. It is widely accepted that the offending vein doesn't necessarily have to be located at TREZ but through the entire course of the nerve up to Meckel’s cave , 11, 20.We did not find typical anatomical features that could either predict or influence the outcome regarding pain improvement or resolution in any form. Neither classic microvascular decompression (interpsiton/transposition) nor sacrificing the offending vein made any difference in outcome. Facial numbness is a typical complication after surgery and strongly associated with venous compression type C and D according to Inoue et al. .


Opioids remain the mainstream therapy for post-surgical pain. The choice of opioids administered by patient-controlled intravenous analgesia (PCIA) for thoracoscopic lung surgery is unclear. This study compared 3 opioid analgesics for achieving satisfactory analgesia with minimal emesis (SAME).This randomized clinical trial enrolled patients scheduled for thoracoscopic lung surgery randomized to receive 1 of 3 opioids for PCIA: oxycodone (group O), hydromorphone (group H), and sufentanil (group S). The primary outcome was the proportion of subjects achieving SAME, i.e., no-to-mild pain (pain score < 4/10) with minimal nausea/vomiting (PONV score < 2/4) when coughing during the pulmonary rehabilitation exercise in the first 3 postoperative days.P = 0.043), but no difference was observed between pairwise group comparisons. Patients in groups O and H had lower pain scores when coughing on the second day after surgery than those in group S, both with mean differences of 1  and 3 vs 4, P = 0.009 and 0.039, respectively). The PONV scores were comparable between three groups (P > 0.05). There were no differences in other opioid-related side effects, patient satisfaction score, and QoR-15 score among three groups.Of 555 enrolled patients, 184 patients in group O, 186 in group H and 184 in group S were included in the final analysis. The primary outcome of SAME was significantly different among group O, H and S .This study was registered at (The online version contains supplementary material available at 10.1186/s12871-022-01785-4. Although minimally invasive techniques are increasingly popular, postoperative pain is one of the most common complaints from patients undergoing video-assisted thoracoscopic surgery (VATS). Of note, patients can still experience moderate-severe pain after VATS , 2. PainCurrent approaches for postoperative pain management, are increasingly centered on non-opioid approaches after VATS. For instance, epidurals have classically been recognized as the gold standard for pain management in thoracic surgery  and moreOxycodone, hydromorphone and sufentanil are potent opioid analgesics used to treat postoperative pain , 19. HowWe designed a randomized controlled trial (RCT) to compare 3 opioids PCIA for achieving satisfactory analgesia with minimal emesis (SAME) in patients undergoing thoracoscopic lung surgery.This three-arm RCT was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of West China Hospital of Sichuan University . The protocol was registered in the Chinese Clinical Trials Registry . All participants provided written informed consent before enrollment. The study protocol followed the CONSORT guidelines.We recruited participants scheduled VATS resection of lung nodules at West China Hospital of Sichuan University, from April 2021 to November 2021. Patients were eligible for participation if they met the following criteria: age 18 years or older; American Society of Anesthesiologists statuses I-III; elective thoracoscopic lung surgery. Exclusion criteria were as follows: refusal to participate in the study, known allergies to study drugs or sulfonamides, renal or liver impairment, sleep apnea syndrome, chronic obstructive airway disease, bronchial asthma, ischemic heart disease, pulmonary heart disease, active gastrointestinal ulcer or bleeding or inflammatory bowel disease, pregnancy or breast-feeding, refuse to use PCIA.Eligible patients were randomly assigned to one of three experimental groups  in a 1:1:1 ratio by computer-generated random permuted blocks of size 6. The blocks of random numbers were generated and put in opaque envelopes, each with a screen number on the front of the envelope. Participants, surgeons, and evaluators assessing outcomes were blinded throughout the study. The investigator opened the envelopes before the end of the surgery and prepared the PCIA pump accordingly. The analgesic pump was put into an opaque portable bag and connected at the end of the surgery. The nurses in the post-anesthesia care unit (PACU) and ward who was responsible for the PCIA knew the grouping.All participants were monitored with electrocardiogram, pulse oximetry, bispectral index electrodes and noninvasive blood pressure. Anesthesia management protocol was based on guidelines for enhanced recovery after lung surgery . GeneralPCIA was applied to all patients for postoperative pain relief. Patients were randomly assigned to receiving PCIA containing oxycodone 0.5 mg/ml (group O), hydromorphone 0.05 mg/ml (group H) or sufentanil 0.5 μg/ml (group S) combined with tropisetron 5 mg in 100 ml normal saline. The PCIA was set to deliver 4 ml boluses, a 10-min lockout window, no basal infusion dose. All patients in the study were informed beforehand of the PCIA method in the pre-anesthetic appointment. Patients were instructed to press the PCIA in case of emerging pain. PCIA was maintained until patient was discharged from hospital, liquid used up with no request for further PCIA, or withdrawal due to adverse events. Parecoxib i.v. 40 mg was administered every 8 h in the first 3 days after surgery (flurbiprofen 50 mg if contraindicated). If there were numerical rating scale (NRS) pain scores > 3 and no pain relief by pressing the PCIA, the patient was administered i.v. dezocine 5 mg as rescue analgesics. PONV score ≥ 2 were treated with i.v. metoclopramide 10 mg.The primary outcome was defined as the proportion of subjects achieving SAME, i.e., no-to-mild pain (pain score < 4) with minimal nausea/vomiting (PONV score < 2) when coughing during the pulmonary rehabilitation exercise in the first 3 postoperative days. Pain score was assessed on an 11-point NRS , 4 ≤ NRS < 7 (moderate pain), NRS ≥ 7 (severe pain), 10 = worst pain imaginable). The PONV score was defined as follows: 0 = no nausea, 1 = mild nausea (no treatment needed), 2 = moderate nausea or retching (may need treatment), 3 = frequent vomiting (controlled with anti-emetics), and 4 = severe vomiting (uncontrolled with anti-emetics). Key secondary outcomes included pain scores at rest and when coughing, and PONV scores within 3 days after surgery. Other secondary outcomes included the proportion of SAME at rest in the first 3 postoperative days, the total dose of opioids in morphine equivalents, the dose of opioids of PCIA in morphine equivalents, quality of recovery-15 (QoR-15) score, other opioid-related adverse events, and expectation pain score fulfilled on POD1-3, patient satisfaction score on pain control and the length of stay (LOS) in hospital.At the end of surgery, the patients were transferred to PACU. Pain scores and PONV scores were assessed after tracheal tube removal at PACU by a trained nurse. After the patients returned to the ward, the pain score and PONV score were immediately assessed by a trained nurse, and then assessed every 4 h. Within the first 3 days after surgery, patients were followed up by a trained investigator between 17:00 to 19:00 every day. The investigator recorded the patient’s average pain score and PONV score within the past 24 h according to the nursing records. Patient satisfaction score (0 = dissatisfied and 100 = very satisfied) on pain control, QoR-15 score (ranging from 0 to 150), other opioid-related adverse events, and expectation NRS fulfilled by asking the patient whether the pain was acceptable or not were also recorded.The sample size estimation was based on previous research data in our center, in which.the proportion of SAME was 33% in patients undergoing thoracoscopic lung surgery with PCIA  [P < 0.05.IBM SPSS Statistics software (version 26.0) was used for statistical analysis. The analysis was conducted by intent-to-treat. Per-protocol analysis of the primary outcome was also performed. Normality of the data was evaluated using the Kolmogorov–Smirnov test. Normal continuous baseline variables are presented as the mean (standard deviation [SD]), and non-normal continuous variables are presented as median and quartiles, categorical variables are presented as numbers and percentages. For global group comparisons of variables, continuous data were analyzed using one-way analysis of variance or the Kruskal–Wallis test as appropriate, and the R*C Chi-square test was used for comparison of proportions. Specifically, generalized estimating equations with robust standard error estimates were used to account for repeated measures of pain scores and QoR-15 scores. For primary and secondary outcomes, if R*C Chi-square test or the Kruskal–Wallis test results were significant, pairwise group comparisons were performed by Chi-square test or Mann–Whitney U tests, and Bonferroni correction was applied. The level of statistical significance was set at Of 1371 potentially eligible patients, 555 patients were randomized into the study , but no difference was observed between pairwise group comparisons; The SAME on POD 1 were significantly different among three groups , but no difference was observed between pairwise group comparisons; On POD 2, groups O  and H  had significantly more patients achieving SAME than group S; On POD 3, the proportion of patients achieving SAME were similar among three groups  , P = 0.009 and 0.039, respectively)   and 3 vs 87.1% in group H vs 85.9% in group S, P = 0.24). Group H took less opioid both in total dose  mg vs 36.5 mg, P = 0.004) and in PCIA  mg vs 24.0 mg, P = 0.007) in morphine equivalents than group S. Subjects in all groups achieved a very good satisfaction score and QoR-15 score. Other opioid-related adverse events also were not significantly different among groups. Group O had shorter LOS after surgery than Group H  days vs 4 days, P = 0.043). The expectation NRS fulfilled  within 3 days after surgery were comparable among three groups (P > 0.05) . Considering the analgesic efficacy and the adverse event profile of opioids, our study focused on the proportion of satisfactory analgesia with minimal emesis within the first 3 days after surgery. We found a 38% relative (11.4% absolute), or 35% relative (10.4% absolute) increase in the proportion of patients achieving SAME when compared oxycodone or hydromorphone with sufentanil, respectively, which was not statistically significant but, in our view, clinically relevant. Of note, more than half of patients receiving oxycodone (59.2%) or hydromorphone (57.5%) achieving SAME in the second day after surgery, and the differences reached statistically significant when compared to patients receiving sufentanil (43.5%). In addition, oxycodone or hydromorphone was superior to sufentanil for acute pain when comparing pain scores when coughing. In our view, this finding supported that the oxycodone or hydromorphone was superior to sufentanil for PCIA because clinically relevant benefits were detected. However, the existing studies that have compared oxycodone, hydromorphone and sufentanil in surgical patients are limited. A recent meta-analysis evaluated the acute postoperative analgesic efficacy of intravenous oxycodone against other strong opioids in adult patients . There wAlthough PONV is typically considered an inherent side-effect of opioid-based analgesia, our study showed that more than 90% patients had no or mild nausea (PONV score < 2) within the first 3 days after surgery. A previous study reported that a lower dose background infusion of oxycodone was associated with fewer PONV . The relOur findings suggested that the incidence of other opioid-related adverse events was not significantly different among oxycodone, hydromorphone and sufentanil. Our reported incidence of constipation 33.9%) and dizziness (22.9%) were similar to Lee et al.’s study, in which constipation (28.9%) and dizziness (21.1%) were two most common side effects with opioid PCIA after thoracoscopic lobectomy . Pruritu.9% and dThis study had several limitations. First, as the treatment effect of oxycodone or hydromorphone was lower than anticipated (a relative increase of 50%) compared to sufentanil, the trial was possibly underpowered to assess the primary outcome, and therefore, should be considered a pilot study. Therefore, no strong conclusions could be drawn from the present work. Consequently, further studies are needed to confirm the superiority of oxycodone and hydromorphone when compared to sufentanil for PCIA. Second, a small proportion of patients were not strictly following the optimal pain treatments recommended by PROSPECT for VATS, including intercostal nerves block (21%) and NSAIDs intra-operatively (8.8%) . HoweverGiven clinically relevant benefits detected, PCIA with oxycodone or hydromorphone was superior to sufentanil for achieving satisfactory analgesia with minimal emesis in patients undergoing thoracoscopic lung surgery. The PCIA with opioids is considered to have potential as a supplement to multimodal analgesia with technical simplicity and less invasiveness, and may be worthy of further research.Additional file 1. Comparison of postoperative outcomes in the per-protocol analysis. Dataare presented as the median (IQR) or number (%). Abbreviations: IQR, interquartilerange; PCIA, patient-controlled intravenous analgesia; POD, postoperative day;PONV, postoperative nausea and vomiting; QoR-15, Quality of Recovery-15questionnaire; SAME, satisfactory analgesia with minimal emesis.Additional file 2. Expectation on pain fulfilled rate. POD, postoperativeday. A. Expectation on cough fulfilled; B. Expectation at rest fulfilled; C.Expectation on average pain fulfilled.


To investigate the efficacy of bilateral 4-quadrant laparoscopic-assisted transversus abdominis plane (BLTAP) block in laparoscopic cholecystectomy (LC).This study was carried out at Private Medicabil Hospital, Bursa, Turkey, between September 2021 and March 2022. Patients were randomly divided into 4 groups : i) the standard analgesia (SA) group received the block and port-site infiltration with normal saline (NS); ii) the local anesthetic group received the block with NS and port-site infiltration of bupivacaine; iii) the unilateral laparoscopic-assisted transversus abdominis plane (ULTAP) block group received 2-quadrant block with bupivacaine on the right and NS on the left and port-site NS infiltration; and iv) the BLTAP block group received bilateral bupivacaine and port-site NS infiltration. Postoperative 1-, 3-, 6-, 12-, and 24-hours visual analog scale (VAS) pain scores at rest and during cough, opioid requirement, presence of nausea and vomiting, and satisfaction scores were recorded.The one-hour VAS score at rest was lower in the BLTAP block group than in the SA and ULTAP block groups. The change in VAS score was higher in the SA group than in the BLTAP block group. During cough, the one-hour VAS score was lower in the BLTAP block group than in the SA group. There were no differences among groups in other parameters.Bilateral 4-quadrant laparoscopic-assisted transversus abdominis plane block technique is more effective than SA, local anesthetic infiltration, and ULTAP block in preventing early postoperative pain after LC.Clinicaltrials.gov No.: NCT04641403 Laparoscopic cholecystectomy (LC) is a commonly carried out surgical procedure associated with moderate pain, particularly in the early period after surgery. Pain caused by LC is usually managed with standard intravenous (IV) analgesia in the form of paracetamol, nonsteroidal anti-inflammatory drugs, and low-dose opioid administration, depending on the level of pain. With the increase in the number of outpatient surgical procedures and the introduction of accelerated recovery protocols, various approaches, such as local anesthetic infiltration, regional anesthesia techniques, and different block interventions, have been increasingly used and are included in postoperative pain management guidelines. It was first carried out blindly by Rafi. Various techniques have been developed up to date for the TAP block. The block is commonly carried out under the guidance of ultrasound (US). When carried out under US guidance, the rate of local anesthetic delivery to the proper plane is higher. However, it also has drawbacks, such as the requirement for equipment, practitioner, experience, and a longer learning curve. Several studies, reviews, and meta-analyses have also demonstrated the efficacy of TAP block for reducing pain and opioid consumption after different abdominal surgeries.The transversus abdominis plane (TAP) block is carried out by blocking the T6-L1 somatic nerves innervating the anterior abdominal wall from the parietal peritoneum to the cutaneous tissue in the neurofacial space between the internal oblique muscle and transversus abdominis muscle. As a relatively simple and practical method, LTAP has been thought to have major advantages for post-LC pain management in terms of time, resources, and cost. However, randomized controlled studies carried out on this issue in different centers have yielded different results. The different results may be attributed to the differences in the techniques used . There are debates regarding the administration areas and number of block techniques. For example, it has been reported that only blocking the right side of the abdomen will be sufficient for LC. Moreover, the study by Elamin et al, reported that TAP block should be applied to both subcostal and lateral areas as bilateral 4 quadrants . The results of these different studies have created a controversy on the use of unilateral laparoscopic-assisted TAP (ULTAP) and BLTAP blocks in LC cases.Laparoscopic-assisted TAP (LTAP) block was carried out in 2011 before laparoscopic nephrectomy as a technique that combines the advantages of both techniques and can be easily carried out by a surgeon. This prospective randomized study aimed to determine the efficacy of BLTAP block over other postoperative analgesia techniques  in LC cases.In routine practice, our center employs an approach of gradual administration of IV paracetamol, nonsteroidal anti-inflammatory drugs, and, when necessary, IV tramadol for the management of post-LC pain. However, TAP block or port-site local anesthetic infiltration can also be used depending on the surgeon’s preference. Studies on this subject do not provide a clear answer regarding the efficacy of TAP block application over conventional pain applications and the quadrants that should be applied with this technique.The study was designed as a prospective, randomized, controlled, and participant-blind study and carried out at the General Surgery, Anesthesiology, and Reanimation Departments of Private Medicabil Hospital, Bursa, Turkey, between September 2021 and March 2022 in adherence to the Declaration of Helsinki and the principles of Good Clinical Practice. The approval for the study was obtained from the Clinical Research Ethics Committee of Bursa Uludag University, Faculty of Medicine, Bursa, Turkey (no.: 2011-KAEK-26/55)., who developed major intraoperative complications, who had a history of severe allergy, who had chronic analgesic use, and in whom the TAP technique was not properly carried out were excluded from this study.Patients aged 18-70 years with American Society of Anesthesiologists (ASA) scores of 1 and 2 who underwent conventional 4-quadrant LC were included in the study. Those who refused to participate in the study, who underwent emergency surgery or open cholecystectomy, whose surgery was converted to open surgery, who had a body mass index of >40 kg/mPatients were randomized to the groups immediately before surgery using a computer-generated random number table and the surgeon was informed regarding the technique to be used for each patient. Patient’s data were recorded on a previously prepared form, and there was no record in this form to suggest the group of the patient. Although the surgeon and surgical team were not blinded, the anesthesia team and clinical nurses who carried out and recorded the postoperative assessments were blinded to the group of patients. In all groups, postoperative pain management was carried out by teams  who were blinded to the patient group by following standard orders, and the surgeon was not involved in this process. These forms were collected by the research coordinator nurse immediately before discharge and kept until the end of this study. The executive team was blinded of the results until the end of this study.Before starting this study, educational materials containing theoretical information, shape, and video on the regional anatomy and block administration were provided to the entire team who would carry out the block to standardize the level of knowledge. This study was started after the pre-application of 10 patients by the surgical team. All surgeries were carried out by 2 staff (HO and MN). Three 20 ml injectors were kept ready on the operating table for all patients undergoing LC included in this study, and normal saline (NS) or local anesthetic was withdrawn into the injector depending on the study group. In the BLTAP block group, the local anesthetic was diluted with saline and prepared as 40 ml of 0.25% bupivacaine . For the port-site injection of local anesthetic and ULTAP block, 20 ml of 0.5% bupivacaine  was used; thus, the total dose of local anesthetic was similar between the 2 groups.Patients were randomly assigned to the following groups: Group 1 : SA group received the block and port-site infiltration with NS. Group 2 : this group received the block with NS and port-site infiltration of anesthetic. Group 3 : following the port-site infiltration with NS, unilateral right-side 2-quadrant block  was carried out using bupivacaine, and left-side 2-quadrant block was carried out with NS. Group 4 : following port-site infiltration with NS, a bilateral 4-quadrant block  was carried out using bupivacaine. The administration techniques and dosages are shown in  In the BLTAP group, TAP block was carried out at 4 points: bilateral subcostal area and bilateral triangle of Petit. In the ULTAP group, the blocks were applied at the same points  only on the right side (2-quadrant block). The procedure sites and administration techniques are shown in The first port was inserted through the umbilicus after the anesthesia was induced, and a standard pneumoperitoneum pressure of 12 mmHg was established. The block was carried out by first inserting a 22-G needle just above the iliac crest through the midclavicular line posteriorly into the triangle of Petit under the direct view of the laparoscopic camera. The needle was then inserted below the costal arch through the midclavicular line toward the anterior axillary line into the subcostal plane. The block needle was advanced under direct view until the 2 pops were felt, and the extraperitoneal space was accessed avoiding puncture of the parietal peritoneum. The needle was withdrawn about 0.5 cm to infiltrate the thin transversus abdominis muscle fibers in the area. The position of the needle tip in this area was confirmed by visualization of Doyle’s bulge and the spread of the local anesthetic.Laparoscopic surgery was carried out using the conventional safety technique with 2 trocars sized 5-mm and 2 sized 5-mm. The pouch was removed through the epigastric port using an endobag. The 10-mm trocar sites were closed using absorbable sutures in the fascial plane.2 and 50% air to keep minimum alveolar concentration of sevoflurane as 2. To evaluate the depth of anesthesia, the BIS value was maintained between 40-60. Pressure-controlled mechanical ventilation was carried out by maintaining ETCO2 between 32-35 mmHg. Before the patients were awake, 1 g acetaminophen  and 50 mg tramadol  were administered intravenously. Patients were then transferred to the general surgery ward when they could hold their heads straight for 5 seconds, with a 30-minutes modified Aldrete score above 8.After the transfer of patients to the operating room, an IV vascular access was established with a 22-gauge cannula, and 0.001 mg/kg midazolam was intravenously administered for sedation. Standard anesthesia monitoring included electrocardiogram (ECG), noninvasive blood pressure, peripheral oxygen saturation (SpO2), end-tidal carbon dioxide (ETCO2), and bispectral index  measurements. For the induction of anesthesia, 0.2 mg/kg fentanyl , 0.6 mg/kg rocuronium bromide , and 1-2 mg/kg propofol  were induced by titration. The depth of anesthesia was maintained with a mixture of 50% OA standard protocol was followed for postoperative analgesia in all groups. Acetaminophen 1 g  was gradually administered every 6 hours depending on the level of pain, while diclofenac sodium was intravenously administered every 12 hours when required. Intravenous tramadol 50 mg  was given as a rescue analgesic to patients with a pain score higher than 4.Data on age, gender, height, weight, comorbidities, smoking status, length of hospital stay, operative time, intraoperative fluid volume, and complications of patients were collected using a standard form, after which intergroup comparisons were carried out. The primary outcome of this study was postoperative 1-, 3-, 6-, 12-, and 24-hours pain scores on the visual analog scale (VAS) during rest and cough.The secondary outcomes included the requirement for rescue analgesics, pre-discharge patient satisfaction , presence of shoulder pain, nausea and vomiting, and discharge duration exceeding 24 hours.The mean postoperative one-hour pain scores on VAS and the rates of rescue analgesic use of 20 patients who underwent surgery prior to the study were determined. Based on the values obtained, it was determined that there should be 35 patients in each group, with a reduction in the pain scale score of 33% following LTAP block, at a significance level of 5% and a statistical power of 80%. In order to account for potential exclusions following randomization, this study included 40 patients per group. All patients gave informed consent. G*Power software was used to for power analysis.The consistency of normally-distributed continuous variables was examined with the Kolmogorov-Smirnov test. Continuous variables were presented as mean ± standard deviation (SD) or median (interquartile range [IQR]). If the variables followed a normal distribution, analysis of variance was carried out to make comparisons among groups; otherwise, the Kruskal-Wallis test was considered with the Dunn-Bonferroni test for pairwise comparisons. To compare VAS scores, the one-hour VAS scores were compared among groups; the difference in the VAS scores measured at 3-, 6-, 12-, and 24 hours compared to one-hour measurement was calculated; and these measurements were compared. In this way, the change in the scores (∆) obtained in the relevant periods according to the one-hour measurement was examined. Categorical variables are presented as numbers and precentages values and compared among groups using the Chi-squared or Fisher-Freeman-Halenda test. The Statistical Package for the Social Sciences, version 25.0  was used for the statistical analyses.p>0.05).This study included 171 patients scheduled for LC. Eleven patients who did not meet the study criteria and refused to participate in this study were excluded from randomization. A total of 21 patients were excluded from the study for various reasons after randomization. Thus, 34 patients were included in the SA group and 35 patients in other groups. The Consolidated Standards of Reporting Trials diagram for this study is shown in p=0.002). The subgroup analyses showed that the BLTAP block group had a lower one-hour VAS score at rest compared to the SA block group (p=0.002) and the ULTAP block group (p=0.0245). The comparison of the changes in scores calculated by obtaining the difference according to the 1-hour score among the groups revealed a statistical difference in the change observed in the 24-hours score to the 1-hour score (p=0.033). The SA group had a higher change in VAS score compared to the BLTAP block group (p=0.038).The analysis of the one-hour pain scale scores at rest revealed a statistical difference among the groups (p=0.004). Based on the intergroup comparison, the 1-hour VAS score in the BLTAP group was lower than that in the SA group (p=0.002). The groups were similar in terms of the change in VAS scores from the 1-hour score. The VAS scores of all groups at rest and during cough are shown in The 1-hour pain scores measured during cough were also significantly different among the groups  was used as a rescue analgesic. Among all groups, only one dose was sufficient in the patient groups that required rescue analgesic use, and none of the patients required a second dose. There were no significant differences among the groups in terms of rescue analgesic use.None of the groups developed postoperative vomiting, and there were no significant differences among groups in terms of the presence of nausea, patient satisfaction scores, complaints of shoulder pain, and discharge duration exceeding 24 hours. The secondary outcomes are shown in The results of this study comparing the efficacy of 4 different techniques in the management of post-LC pain demonstrated that the BLTAP block was more effective in preventing postoperative 1-hour pain compared to standard IV analgesia, port-site infiltration of local anesthetic, and the ULTAP block. However, there was no difference in the pain values measured subsequently and the use of rescue analgesics among the 4 techniques. used this technique in their prospective randomized controlled study after laparoscopic ventral hernia repair and found that the technique reduced pain scores and opioid use. The efficacy of the LTAP block was first prospectively randomly tested by Elamin et al after LC. This study showed that the technique was more effective than port-site infiltration of local anesthetic in reducing pain scores in the first 6 hours, but this technique had no difference with port-site infiltration of local anesthetic in terms of opioid requirement. However, there are also different study results on the efficacy of the technique after LC. A recently published study by Siriwardana et al found an opposite result and showed that LTAP block did not decrease postoperative 6-hours pain scores and opioid use compared to local anesthetic administration. A prospective, randomized, and double-blind study by Houben et al investigating the efficacy of bilateral US-guided TAP block after LC, found that it had no advantage over SA in terms of parietal and visceral pain, but it decreased the requirement for intraoperative sevoflurane to some extent. Takimoto et al reported that the addition of a subcostal block to a lateral block increased the early analgesic efficacy in patients who underwent LC. Considering these studies, the local anesthetic injection was administered to 6 points in Fields et al’s study, whereas it was administered to 4 points in Elamin et al’s study. The block technique we used was the laparoscopic-assisted form of the US-guided 4-quadrant dual-block technique defined by Chen et al. These results suggest that the multi-point injection block is more effective in providing adequate analgesia.The efficacy of the LTAP block has been investigated using different surgical procedures. Field et al in terms of the techniques used and results produced. However, there are some differences with this study. First, our study comprised the SA, which is commonly used in clinical practice, and right-sided ULTAP block groups, which is another controversial topic. Another difference is that local anesthetic to the first port site and intraperitoneal area was not induced in all groups in our study. The main reason for this was to better observe the efficacy of the TAP block. Moreover, postoperative evaluation of visceral pain that is intended to be reduced by intraperitoneal administration is difficult and subjective. Simultaneously, the contribution of this type of pain to postoperative pain is minimal in laparoscopic procedures. This means that higher doses of local anesthetics should be induced.Our study demonstrated that the BLTAP block was more effective in reducing postoperative 1-hour pain scores both during rest and cough compared to conventional IV analgesia and ULTAP block in LC cases. However, the BLTAP block had no difference with the other techniques in terms of opioid requirement for pain. Our study is similar to that of Elamin et al investigating the spread of local anesthetic in the posterior, lateral, and subcostal approaches with magnetic resonance imaging showed that there was a more anterior spread in the lateral and subcostal injections, and that the blockade could be variable and nondermatomal. Similar results were also found in Støving et al’s study, suggesting that carrying out a lateral TAP block alone would not be an adequate approach, especially for midline incisions. The subcostal approach to be carried out more medially would provide a spread of local anesthetic agent in a more cephalad direction and could also block the segmental thoracic intercostal nerves. However, an isolated subcostal block alone may fail to block the lateral anterior axillary line.Several studies have shown that local anesthetic agents have a more limited spread in isolated lateral and subcostal blocks; therefore, both sites should be blocked for complete and long-term blockade of the T6-L1 thoracolumbar nerves. The study of Carney et al using the 4-point approach, and it was first called the 4-quadrant TAP block by Niraj et al. Borglum et al studied the dermatomal sensory anesthesia and spread characteristics of the US-guided 4-point injection technique that they used in 8 healthy volunteers. In this study, the lateral TAP block produced a dermatomal block from T10 to T12 and further extended the subcostal injection block up to T9-T7. Sondekoppam et al examined the lateral medial dual block in 9 cadaver series and found that the segmental spread was between T7-L1, similar to the results of Borglum’s study. It was concluded that the blockade of the lateral compartment alone was not significantly likely to anesthetize the lateral cutaneous nerve. Another study investigating the efficacy of port-site local anesthesia administration, SA, and US-guided unilateral TAP block after LC showed that unilateral TAP caused less pain and less tramadol use than the other 2 groups. However, no bilateral block group was included in this study. In addition, umbilical and epigastric port sites could often pass to the other side of the abdomen in LC procedures. Our study showed that the ULTAP block was ineffective in relieving pain. Therefore, we believe that bilateral administration would be more effective than unilateral administration.The dual block technically combines the lateral/posterior TAP block with the subcostal approach, producing a block that involves both the upper and lower abdomen. It was first carried out by Borglum et al Laparoscopic cholecystectomy is a minimally invasive procedure, and the issue of pain is more significant in this procedure, especially in the first few hours. Our study demonstrated that the problem of pain in patients who received conventional analgesia was evident in the first hour, which was then significantly reduced. The SA group had a higher reduction in 24-hours pain score at rest versus the first hour compared to other groups. This result is attributed to the high initial pain score in the SA group and the significant reduction in pain score at 24 hours using all methods. The use of bupivacaine for the block provided sufficient effect in the first one hour. We believe that bupivacaine alone is sufficient for this surgical technique. The results of our study showed no difference in rescue analgesic use among the groups. None of the patients required a second dose. It is likely that LC is not an appropriate surgical method to compare the long-term effectiveness of block applications with the need for rescue analgesics. It would be more significant to investigate the effectiveness of block applications in these patients using other surgical methods.Another controversial issue is the type of anesthetic agent induced. Liposomal bupivacaine has been indicated to be longer-acting and more effective. It is a relatively new agent, which is not always easily accessible. The addition of dexamethasone is another approach. Although several studies have shown that the efficacy of both procedures is extended, the results remain controversial.The surgeon carrying out the procedure could not be fully blinded in practice. However, this problem was attempted to be solved by standardizing postoperative pain management; blinding the team (anesthesia team and clinic nurses) implementing the pain management, assessments, and recordings of the patient group; providing these data to the data collectors after the discharge of the patient; and evaluating all data at the end of this study. Second, the study included only patients with ASA scores of 1 and 2, while those with ASA scores of 3 and 4 were excluded as they used several different drugs and the technique could pose difficulties in evaluating VAS scores. Nevertheless, this group of patients may be the subject of another study.In conclusion, the results of this study suggest that bilateral 4-quadrant LTAP block is an easy-to-carry out and practical technique for reducing pain in the first hour after LC. Our study has the following most important result: the TAP block should be applied to the 4 quadrants to have a sufficient effect in preventing post-LC pain. The efficacy of the block on pain in later hours and rescue analgesic use should be investigated using different surgical methods. New studies comparing different block methods will provide more detailed information in determining the block method that is more effective and applicable.


ANO1, ANO3, HCN1, KCNA2, KCNA4, KCNK18, KCNN1, KCNQ3, KCNQ5, KCNS1, TRPA1, TRPM8, TRPV1, TRPV3 and TRPV4 variants by single-molecule molecular inversion probes–next-generation sequencing. These patients did not have genetic variants in SCN3A, SCN7A-SCN11A and SCN1B-SCN4B. In twenty patients , a potentially pathogenic heterozygous variant was identified in an ion-channel gene (ICG). Variants were present in seven genes, for two patients (0.5%) in ANO3, one (0.2%) in KCNK18, two (0.5%) in KCNQ3, seven (1.7%) in TRPA1, three (0.7%) in TRPM8, three (0.7%) in TRPV1 and two (0.5%) in TRPV3. Variants in the TRP genes were the most frequent , partly in patients with high mean maximal pain scores VAS = 9.65 ± 0.7 (n = 4). Patients with ICG variants reported more severe pain compared to patients without such variants (VAS = 9.36 ± 0.72 vs. VAS = 7.47 ± 2.37). This cohort study identified ICG variants in neuropathic pain in SFN, complementing previous findings of ICG variants in diabetic neuropathy. These data show that ICG variants are central in neuropathic pain of different etiologies and provides promising gene candidates for future research.Neuropathic pain is a characteristic feature of small fiber neuropathy (SFN), which in 18% of the cases is caused by genetic variants in voltage-gated sodium ion channels. In this study, we assessed the role of fifteen other ion channels in neuropathic pain. Patients with SFN (n = 414) were analyzed for  Neuropathic pain (NeuP) is defined as a pain condition usually caused by progressive nerve disease . NeuP sySCN9A, SCN10A and SCN11A have been reported in several pain-related diseases, including SFN [SCN3A, SCN7A-SCN11A and SCN1B-SCN4B, increased the number of patients with NeuP with an identified  underlying cause to 18.1% [In the last two decades, alterations of voltage-gated sodium ion channels (VGSCs) have been reported to be caused by genetic mutations in the underlying genes ,11,12,13ding SFN ,15, addi2+-activated Cl- channels, also known as anoctamins (ANO) [In the literature, other ion channels’ genes (ICGs) have also been reported in pain modulation, mainly transient receptor potential (TRP) cation channels , potassins (ANO) . TRP chans (ANO) . Kv are ns (ANO) . HCN chans (ANO) . The mosns (ANO) . Moreovens (ANO) .SCN3A, SCN7A-SCN11A and SCN1B-SCN4B genes was negative. We performed single-molecule molecular inversion probes–next-generation sequencing (smMIPs-NGS) to analyze exons and exon–intron junctions and classified the identified variants.In a previous study, we investigated the role of variants in 15 ICG in different patient cohorts with painful and painless DN. GOF and LOF variants were present in both groups, suggesting that ICG variants contribute to NeuP . TherefoANO3 (2946 bp), KCNA2 (1500 bp), KCNA4 (1962 bp), KCNK18 (1155 bp), KCNQ3 (2619 bp), KCNQ5 (2856 bp), TRPA1 (3360 bp), TRPM8 (3315 bp), TRPV1 (2520 bp) and TRPV4 (2616 bp) had an average coverage >90%, and for five targeted gene areas (ANO1 (2961 bp), HCN1 (2673 bp), KCNN1 (1632 bp), KCNS1 (1581 bp), TRPV3 (2376 bp)) the average coverage was at least 84%. Four exons  had poor coverage (<20x/bp) or were completely missing. The calculated capture efficiency of each probe and coverage of on-target regions was reproducible per region, per run and between samples. A total of 49 out of 553 samples were excluded due to low quality of DNA, insufficient number of reads or incomplete clinical information  for a 15-ICG panel were assessed as described previously . The aveormation .SCN3A, SCN7A-SCN11A and SCN1B-SCN4B screening, 19 different potentially pathogenic variants were identified in ICGs. All detected variants were classified as VUS and localized in seven ICG genes: ANO3, KCNK18, KCNQ3, TRPA1, TRPM8, TRPV1 and TRPV3. In total, two missense variants were detected in ANO3, one frameshift variant leading to a shorter protein in KCNK18, two missense in KCNQ3, four missense and two nonsense variants in TRPA1, three missense in TRPM8, three missense in TRPV1, one splice variant in the donor site of intron 9 and one missense in TRPV3 (TRPV3 c.1242+1G>A) was predicted to alter the protein sequence via alternative splicing.Among 414 patients negative for in TRPV3 . All of KCNK18 c.1107del, TRPA1 c.1177C>T and c.1954C>T), the substitution in conserved functional areas of the protein may affect proper functioning. Three variants (TRPV1 c.1348A>G and c.1735C>T and TRPV3 c.2006T>C) were found in transmembrane domains. One variant (ANO3 c.2656A>T) was detected in a linker between transmembrane domains, three variants were located in ankyrin repeats (ANK) (TRPA1 c.932C>A and c.980A>G and TRPV1 c.914T>G), three in the N-terminus (TRPM8 c.665A>G and c.1102C>T), four in the C-terminus  and one in the inositol-phosphate binding site of TRPA1 (c.3136A>G).Although the best predictable functional effect will be lack of the protein due to NMD or truncated, nonfunctional polypeptides , neuropathy duration , positive family history , abnormal TTT  and abnormal skin biopsy   in relation to mean age of onset of neuropathy  . DetaileANO3 variant reported maximal pain (VAS = 9.7), the patient with KCNQ3 c.1885G>A variant reported VAS = 8.7, and the patient with KCNQ3 c.1706A>G reported VAS = 8.5. Interestingly, three out of four TRPA1-positive patients evaluated maximal pain as VAS = 10, which is the highest possible value in the scale. Only one patient carrying the TRPA1 variant, specifically c.2065A>G, reported VAS = 8.6. Therefore, the maximal pain scores in the group of patients having variants in the same gene were higher than those in the subgroup without an ICG/VGSC variant   and the  variant .Several features, including SFN-specific symptoms like a changed sweating pattern, diarrhea, constipation, micturition problems, dry eyes, dry mouth, orthostatic dizziness, palpitations, hot flashes, sensitive leg skin, burning feet, sheet intolerance legs and restless legs were evaluated for the SFN patients . All patSCN3A, SCN7A-SCN11A and SCN1B-SCN4B genes, twenty patients (4.8%) had one potentially pathogenic heterozygous variant in ICG. The detected variants were located in seven genes and were present in two patients (0.5%) in ANO3, one (0.2%) in KCNK18, two (0.5%) in KCNQ3, seven (1.7%) in TRPA1, 3 (0.7%) in TRPM8, three (0.7%) in TRPV1 and two (0.5%) in TRPV3. Most of the detected variants were novel; however, three variants have been reported before. The ANO3 c.3100G>C variant is present in the Human Gene Mutation Database (HGMD) and described as likely disease-causing with questionable pathogenicity in primary torsion dystonia [KCNQ3 variants have been reported in ClinVar; c.1885G>A was reported two times, once as a VUS in benign familial neonatal seizures and as once as likely benign without linking to a specific phenotype, while the c.1706A>G variant was reported as a VUS, and the phenotype was not provided. Our patients did not have complaints typical for dystonia and familial neonatal seizures.In 414 patients with no  pathogenic variants in the dystonia . Two KCNTRPA1 c.3136A>G variant present in a brother and sister with SFN, which was considered as one independent finding. None of the identified ICG variants have been reported before in neuropathic pain, except for the TRPA1 c.1954C>T variant, which we published recently, present in a 73-year-old male diagnosed with painful DN [In our study population, each ICG variant was detected only once, with exception of the inful DN .TRPA1, three (1.4%) in TRPM8, one (0.5%) in TRPV4. Different heterozygous missense VUS were also present in three (1.4%) painful DN patients in ANO3 and two different KCNK18 variants leading to a premature stop codon in two (0.9%) individuals with painful DN [ANO1, HCN1, KCNA2, KCNA4, KCNQ5, KCNN1, KCNS1 and TRPV4. Five of them, KCNA2, KCNA4, KCNQ5, KCNN1 and KCNS1, were also negative for screening in a diabetic neuropathy population [KCNQ3, TRPV1 and TPRV3, which did not appear in painful DN [The frequency of potentially pathogenic ICG variants in our population (4.8%) was slightly lower than the frequency in patients with painful DN (5.4%) . The mosinful DN . Therefopulation . Interesinful DN . TherefoTRPA1 c.3136A>G, leading to channel inactivation [All detected variants were classified as VUS, which reflects the limitations of bioinformatics analysis of novel variants in absence of functional data or segregation in the family ,26. In ttivation .2+-activated chloride channel family involved in pain processing and thermoregulation [ANO3 indirectly inhibits pain signaling via enhancing sodium-activated potassium (SLACK) channels in DRG [ANO3 knockout results in a decreased pain threshold in tested rats, GOF variants are expected in pain-related phenotypes [ANO3 c.2656A>T and c.3100G>C) have been identified in two unrelated subjects. Both of them reported burning pain, allodynia and sheet intolerance. TTT was abnormal in both cases; moreover, a female patient identified cold temperature as a pain-provoking factor. Altogether, it may link the patients’ clinical manifestation with disrupted thermoregulation.Anoctamin 3 is a member of the Cagulation . ANO3 ins in DRG . Since Aenotypes . Consistenotypes . In our KCNK18 c.1107del leading to a frameshift and a shortened C-terminus has been identified in an SFN patient. Although missense and frameshift mutations with a premature stop codon in KCNK18 are linked mainly to migraine, some studies indicate that downregulation of KCNK18 contributes to neuropathic pain [KCNQ3 c.1885G>A and c.1706A>G. Interestingly, both of them had a similar phenotype with numb sensation and burning pain in the feet. In both cases, pain complaints were getting worse at rest. Additionally, both patients had disturbed warm and cold sensation in their feet. However, one patient reported that cold increased and warmth reduced pain symptoms, while the other patient did not indicate a temperature influence on pain. GOF mutations in KCNQ3 are recognized as contributors to pain resilience [Potassium channels are important in regulation of nociceptor excitability in sensory neurons . A heterhic pain ,36. Two silience , therefoTRPA1 (two nonsense and four missense), three missense variants in TRPM8, three missense in TRPV1 and two variants in TRPV3 (one missense and one splice variant). TRPA1 channel activity has been functionally linked to pain hypersensitivity, cold hyperalgesia and mechanical nociception in inflammatory and neuropathic pain models [TRPA1 has been associated with familial episodic pain syndrome. The TRPA1 R919* variant is segregating in a family with the cram-fasciculation syndrome [TRPA1 VUS was diverse in our cohort; however, the most common complaints were numb sensation, tingling and burning pain. Four out of seven patients reported pain increase after exercise, and all the patients with performed TTT had abnormal TTT values.Variants located in the TRP genes constitute the largest group of variants identified in our study cohort. TRP channels constitute a large, divergent gene family with a well-documented role in mediating nociceptive behaviors in response to thermal, chemical and osmotic stimuli . In totan models ,40,41. Tsyndrome ,43. Intesyndrome , and witTRPM8. Additionally, the patient with c.665A>G VUS reported increased pain due to warm temperature. As TRPM8 is a modulator of cold sensation and a potential target for neuropathic pain treatment [Three different heterozygous VUS have been detected in patients with disturbed thermal sensation  in reatment , those vTRPV1 and TRPV3 are heat-activated proteins involved in thermosensation and pain perception [TRPV3 activation plays a role in enhanced itch sensation [TRPV3 variant (c.20006T>C combined with itch episodes and a splice-site variant c.1242+1G>A r.spl?), and three patients were heterozygous for a missense variant in TRPV1 (c.914T>G or c.1348A>G or c.1735C>T). Two of them reported increased pain complaints during rest, which might interfere with night rest. Interestingly, no pain change was reported in response of warm/cold temperature. The literature indicates that upregulation of TRPV1 increases amplification of pain signals [TRPV1 has been linked to neuropathic pain [TRPV1 missense variants localized in transmembrane domains have been reported in diabetic neuropathy patients without pain [rception . In addiensation . In our  signals . Consisthic pain . On the out pain , which h+ influx produced by gain-of-function Nav1.7 mutations as a trigger for calcium-importing reverse Na+/Ca2+ exchange that can contribute to axonal degeneration [TRPA1 reported very severe pain (mean max pain VAS = 9.65 ± 0.7), and three of them gave VAS = 10, which is the highest possible score. These data are consistent with a previous study showing that mean maximal pain was higher for painful DN patients with an ICG variant vs. painful DN without an ICG variant [Due to the small number of patients with an ICG variant, it is difficult to draw a definite conclusion whether these patients had more severe clinical manifestations in relation to basic clinical features or SFN-SIQ when compared to those of patients without an ICG/VGSC variant. It seems that patients with an ICG variant tended to have more frequent abnormal skin biopsies and a shorter duration of neuropathy; however, statistical significance was not reached for any of these features. There is evidence implicating enhanced Naneration ; further variant .SCN3A, SCN7A-SCN11A and SCN1B-SCN4B variant screening. Most of the included patients  were Dutch, while 156 (31%) patients were from Italy. The mean age of recruited SFN patients was 54.1 years (SD 14.2 years), with the mean age of complaints onset of 42.2 years (SD 13.6 years). More females than males were present in the study population. There were 59.5% (n = 300) of females and 40.5% (n = 204) of males. In both populations, females were over-represented, with 59.8% (n = 208) females in the Dutch cohort and 59% (n = 92) females in the Italian cohort, respectively. Twenty-three percent of the patients (n = 65) reported positive cases of neuropathy in the family, while negative family history was registered for 77% (n = 217). The data for familial cases of neuropathy was incomplete for 222 patients. More than one-third of the recruited patients had an abnormal skin biopsy .From June 2014 to September 2016, 553 patients diagnosed with SFN were recruited at Maastricht University Medical Center+ (MUMC+), Maastricht, The Netherlands and at Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta (FINCB), Milan, Italy for this study. MUMC+ is a tertiary referral center for SFN in the Netherlands, and FINCB is a national referral center for several neurological conditions, including SFN. Medical history and clinical data were collected and recorded as described previously . The dia® Blood Core Kit . DNA extraction was performed according to the manufacturers’ instructions and stored in −20 °C.Genomic DNA was from blood samples using a NucleoSpin8 Blood Isolation kit  or a QIAamp DNA Blood Maxi Kit, PuregeneThe smMIP-NGS of exonic regions with ±20 bps exon-flanking sequences of the 15 ion channel genes  was perfExonic and ±20 bp exon-flanking intron variants with >20x coverage and an alternative variant call of >30% were included for the analysis. The SNPs with high frequency, defined as dbSNP > 5%, ExAC > 5% and >1% in our Dutch in-house database of 12,244 exomes, were excluded from the analysis. All variants were examined individually, including BAM file visualization and variant interpretation performed in Alamut Visual software . Variants were classified according to the practice guidelines of the Association for Clinical Genetic Science (ACGS) . t-test. Categorical variables were analyzed using the chi-square test or Fisher’s exact test in the case of small counts <5. Statistical significance of <0.05 was applied.The analysis of continuous variables was performed using the independent Student’s KCNQ3, TRPV1 and TPRV3 that were not present in painful DN. Apparently, ICGs are fundamental for both SFN and DN, although the numbers are too small to unambiguously identify gene-or variant-specific manifestations. Although all of the variants were classified as VUS and the consequences of the variation cannot be certainly predicted in silico, they are still promising risk factors for neuropathic pain as well as promising gene candidates for future research.In a well-characterized cohort of patients with SFN, we identified twenty patients (4.8%) carrying a potentially pathogenic variant in ICG. Patients with an ICG variant might have more severe pain than patients without a  pathogenic ICG/VGSC variant. This complements previous results of the analysis of the same ICG in a large cohort of painful and painless DN. Moreover, it extends the list of potential pain-related genes, reporting variants in


Chronic pain is the leading cause of morbidity in the world and is strongly associated with physical and psychological disabilities. In this pandemic, most of the pain care centers are forced to shut their doors leaving patients in dismay and adding to their misery. A systematic review was performed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. All research articles from March 2020 to September 15, 2020, available on PubMed, Google scholar, and EmBase were included in this study. The keywords used for data search were “chronic pain,” “coronavirus,” “pain management,” “COVID-19,” “drugs usage in covid-19,” “recommendation,” and “guidelines”. This review summarizes findings from the current literature available worldwide from different databases regarding guidelines to practice during chronic pain in coronavirus disease (COVID) crisis. This article acts as a specimen on how to handle future pandemics. We concluded that chronic pain management is a fundamental right and telemedicine is the silver lining that can be used for primary, follow-up consultation and to address mental health issues in chronic pain patients. Outpatient department visits should be scheduled using “forward triage.” Pain Interventions should be carried out if urgent or semi-urgent with necessary precautions. Reopening of elective procedures with COVID testing can be planned, considering pain interventions to be usually percutaneous, of short duration, and involving office procedures with minimal aerosol generation. Drugs contributing to immune suppression, for example, strong opioids and steroids, should be avoided. Regenerative therapy can be used instead during pain interventions. Physicians are expected to follow the recommended government guidelines before prescribing any drugs. With so many guidelines and recommendations, a systematic review like this one that summarizes the most noteworthy instructions for pain physicians to practice while chronic pain management in coronavirus disease (COVID) crisis was vital.Drugs like steroids, strong opioids , and non-steroidal anti-inflammatory drugs (which can mask COVID symptoms) should be used cautiously.The drug-dosage adjustments and alternate for immune-compromising treatments are discussed.Guidelines to “re-open” outpatient services and to perform interventional procedures are enumerated.1 shows a huge chronic pain burden in India by the prevalence rate of 19.3%, which translates into 180-200 million adults having chronic pain. All systematic reviews on chronic pain have concluded that there is an association between pain, mental illness, suicide incidence, and decreased life expectancy.Chronic pain patients have the largest global morbidity. The actual burden of chronic pain is diluted due to under-reporting or patients not visiting the medical facility until dismally needed. An Indian study by Saxena et al.Coronavirus disease 2019 (COVID-19) has taken the world by storm and was declared as a pandemic by the World Health Organization (WHO) on January 30, 2020. Numerous preliminary research articles have been published about the rapidly spreading coronavirus and its impact on global health. It is juvenile to think of COVID-19 as the last pandemic. The research done in this time can serve as an example to handle future pandemics. We conducted a systematic review to summarize and critically analyze all published scientific articles regarding chronic pain management in this COVID-19 era.In this systematic review, we aimed to summarize how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacted chronic pain patients (CPP) and pain physicians. A consensus is drawn on how chronic pain management is being practiced worldwide and what preventive measures health care workers (HCWs) can take while providing pain services in this pandemic.role of telemedicine,usage of drugs and their doses during COVID-19 pandemic,precautions to be taken during outpatient department (OPD) visit and during pain interventions.To understand and discuss:Four researchers independently searched through the relevant articles published from March 2020 to September 15, 2020. All the selected abstracts were reviewed and analyzed. The literature for this review was identified by searching the following online databases: PubMed, Google scholar, and EmBase. We searched scientific publications using the keywords “chronic pain,” “coronavirus,” “pain management,” “COVID-19,” “guidelines,” and “recommendations” .2 Ministry of Health and Family Welfare, Government of India website, was comprehensively scrutinized and all relevant recommendations were included.3 Indian Society for Study of Pain position statement for pain medicine practice during the COVID pandemic published on August 3, 2020, was studied.4 This systematic review was performed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. As per the PRISMA statement, a systematic review starts from a focused research question, using clearly stated methods to retrieve, assess, and analyze research on a specific topic of interest.Guidelines from Directors of the American Society of Regional Anesthesia (ASRA), American Academy of Pain Medicine, Spine Intervention Society, North American Neuro-modulation Society, and the World Institute of Pain integrated with the American Society of Anasthesiologists (ASA), and American Academy of Physical Medicine and Rehabilitation published in Pain Medicine journal on April 1, 2020, were extensively analyzed. Furthermore, the WHO database of publications on novel coronavirus was screened for potentially relevant publications.Around 116 articles were found in the PubMed database, 216 in Google scholar, and 165 in EMBASE. Duplicate entries were removed, after which 108 reports remained. Screening of the reports based on the title and abstract led to the exclusion of 86 studies that did not meet the inclusion criteria. Full texts of 22 studies were retrieved and assessed for eligibility and another 6 articles were included after manual search. This led to the exclusion of 15 studies that did not meet the inclusion criteria for various reasons : 6 were 5 Wang et al6 showed that COVID-19 outbreak and mandatory quarantine have also been associated with negative psychological implications which can exaggerate chronic pain. Thus, mental health considerations are highly relevant in COVID times.Receiving pain treatment is a fundamental human right, but due to lockdown/travel restrictions patients are not able to reach OPD services for primary or follow-up visits. The healthcare resources are redistributed toward intensive care units and other COVID-19-dedicated sites. Also, because most of the pain physicians worldwide are anaesthesiologists, they are working in COVID areas, thus reducing the availability of pain facilities and pain physicians. Incomplete refill of medicines leads to inadequate pain relief, which then results in physical and mental suffering. Mental health disorders  are common in patients with chronic pain.7 Quarantined HCWs are more likely to report mental exhaustion, social detachment, feeling of anxiety when treating febrile patients, irritability, sleep disruption, and poor concentration. The probability of alcohol abuse and symptoms of post-traumatic stress disorder also increased for up to 3 years following the episode of quarantine.8 In this ongoing pandemic, both patients and HCWs should be exposed to screening and treatment interventions for mental health problems using online and mobile-based platforms.9In March 2020, the government health authorities of the United States, European Union, United Kingdom, India, and the rest of the world stated that all routine chronic pain services will be shut in view of the pandemic. The majority of pain physicians were quarantined at home or started working as COVID warriors. A survey on pain physician’s burnout during COVID-19 demonstrated that 98% of physician practices were affected by COVID and 91% of physicians felt that it had a significant financial impact.10 There is an enormous potential for cost reduction and time savings with such services. Telemedicine can be used for “forward triage” in COVID times. Using this, the patient is put in touch with the emergency department to discuss respiratory symptoms and with a pain physician for pain symptoms. This allows patients to be screened efficiently and decide if an in-person visit is needed. It is both patient-centered and conducive to self-quarantine, and it protects patients, clinicians, and the community from exposure.12Before the COVID-19 pandemic, telemedicine approaches were being tested but were not prevalent. Suddenly, however, treating patients with non-urgent and long-term conditions in a safe and effective way has become essential. Randomized controlled trials have demonstrated high levels of satisfaction, convenience, and acceptance of e-health services in remotely located patients.14 and China concluded that for patients with different types of chronic pain, telemedicine support in addition to necessary in-person visits.15 In India, the Board of Governors in supersession of the Medical Council of India in partnership with National Institution for Transforming India Aayog on March 25, 2020, came up with telemedicine guidelines for registered medical practitioners (RMP).16 The guidelines state that RMP can practice telemedicine. Modes that can be used include video , audio , text-based and chat-based applications , general messaging/text/chat platforms , and asynchronous communication . A digital trail including summary of patient complaints and supplementary data including images, lab reports, and/or radiological investigations are shared between the doctor and the patient has to be recorded as documentation of proof.Pain physicians from United Kingdom and Australia emphasized shifting focus to e-health17 or the PAIN OUT system in Europe.18 Chronic pain management depends on good clinical history and clinical evaluation. Short Form McGill Pain Questionnaires and Pain Disability Index are examples of electronic pain questionnaires. The validity and dependability of these tests have been proven with significantly more patients reporting electronic versions easier and favored.19 Similarly, many questionnaires for the assessment of patients with chronic low back pain have shown good reliability and moderate validity.20 The advantage of telemedicine is that red flag signs in chronic pain can be picked up easily during online history taking. Although lack of hands-on physical examination is a limitation with telehealth, a modified virtual examination may allow an initial treatment plan to be started.21In addition, many international medical services use web-based systems that have been developed and optimized for people with pain, such as the Collaborative Health Outcome Information Registry (CHOIR) system in the United StatesThe practical issues in telemedicine for CPPs, for example, the absence of apps/video conference programs installed on the patient’s computer/phone, inaccessibility to a high-speed internet connection, an improperly charged mobile phone, laptop, or computer, and lack of apps to record symptoms on a daily basis may lead to failure of the system. Another challenge for telemedicine, especially in Indian government hospitals, includes the inadequate number of functional telemedicine units. All India Institute of Medical Sciences (AIIMS), Rishikesh, Uttrakhand, India, has a dedicated telemedicine OPD that caters to 50-70 CPPs per day in COVID catastrophe.Patients with COVID-19 undergo signiﬁcant immune system changes. The importance of intact immune response to avoid infection and the association between immune system and various drugs has to be kept in mind while prescribing these drugs.22 The target should be not to create an opioid withdrawal state due to scarcity of medication and at the same time avoid abuse of opioids. Morphine and fentanyl have been observed as potent immunosuppressants.24 Based on available data, buprenorphine appears to be the safest to use in immune-compromised or elderly patients.Opioids are the most effective treatment for acute and chronic pain and have been extensively used for both neuropathic and non-neuropathic pain. Opioids act on the autonomic nervous system and hypothalamic–pituitary–ad renal axis and thus inhibit the innate and acquired immune response.26 In patients already receiving opioids, a temporary increase in opioid dose may be provided if desperately needed. But an in-person visit must be scheduled within 2 months to check for opioid tolerance or opioid hyperalgesia. Monitoring of opioid withdrawal in patients is more perplexing during e-health visits. Symptoms like diarrhea, rhinorrhea, abdominal pain, chills and signs like agitation, diaphoresis, piloerection, and possibly even change in pupillary size can be observed remotely during patient interviews but may be difficult to corroborate. However, the physician has to rely on patients or their caregivers to look for classic signs of opioid withdrawal, that is, elevated heart or pulse rate. Non-opioid drugs like clonidine and lofexidine can be prescribed to prevent physical withdrawal symptoms. It is suggested to consider prescribing naloxone in patients with the potential to overdose and counting opioid tablets dispensed over videoconferencing.27 Educating patients and relatives about overdose and withdrawal plays a key role in this tricky situation. Patients with COVID-19 who are receiving opioids can be more susceptible to respiratory depression. It is recommended to carefully monitor respiration and sedation in patients on transdermal opioids (fentanyl), because the rate of absorption with high fever can be unpredictable.28In the United States, health care providers are permitted to issue electronic opioid prescriptions, via telehealth visits, which may reduce the risk of diversion to illicit forms of opioids. Opioid-naïve patients if needed should be started on short-term interim courses. If an opioid requirement is high after 1-2 weeks, an in-person physical examination is recommended.16 states that opioids fall under the prohibited drugs and are to be prescribed via an in-person visit by licensed practitioners only. This is a limitation to telemedicine as many drugs prescribed for CPPs fall in the category of prohibited drugs for e-consultation. AIIMS, New Delhi, India, shifted from prescribing opioid medications from a strict 2-week policy to a 1-month policy and practiced telemedicine to monitor opioid use.29 This was done in the best interest of patients as travel restrictions in India were the biggest barrier for patients to reach the hospital. The same policy is being followed at AIIMS, Rishikesh, Uttrakhand, India.In India, MoFHW30Chronic pain patients consume oral steroids or receive steroid injections for pain syndromes or multiple musculoskeletal diseases. Steroids suppress the immune system and systemic steroids have been associated with infections, including pneumonia. The hypothalamic–pituitary–adrenal axis suppression typically lasts for less than 3 weeks but may last for over 1 month in some individuals. The effects of intra-articular steroids on COVID-19 have not been evaluated; therefore, intra-articular steroids can be used for pain relief when required after assessing the risks and benefits.31 In patients with rheumatoid arthritis, oral use of corticosteroid dose of ≥20 mg (0.5 mg kg-1) prednisolone  per day for more than 4 weeks, corticosteroid dose of ≥5 mg prednisolone  per day for more than 4 weeks plus at least 1 other immunosuppressive medication  or small molecule immunosuppressant  are extremely vulnerable to COVID-19 infection and needs “shielding.”32The Faculty of Pain Medicine of the Royal College of Anaesthetists’ statement issues caution on the safety of steroids injected during the current COVID-19 pandemic.Epidural and other steroid injections can be performed as per clinical conditions during the COVID-19 pandemic with the lowest dose possible. Patients should be educated about immunosuppression and the potential risk for infection. For patients who are already at high risk for SARS-CoV-2 infection or are immunosuppressed, epidural non-steroid  injections may be considered for radicular pain. Considering immunosuppression, oral steroids should not be prescribed as a first-consult drug; but if a patient is already on steroids, then it should be continued. Dose reduction should be considered after evaluating disease conditions.33 On March 18, 2020, the WHO advised patients experiencing COVID-19 symptoms to avoid the use of ibuprofen and other NSAIDS due to the same reasons. However, the effect of NSAIDS on ACE-2 enzyme has not been substantiated by any other reports and multiple regulatory bodies have since refuted this assertion.36 Acetaminophen is an alternative to NSAIDs. When compared in osteoarthritis patients, it is not only less effective but also less toxic than systemic NSAIDs. Hence, acetaminophen is the most appropriate first-line oral analgesic for long-term in these patients.37 Joint guidelines from ASRA/ESRA  recommended that all patients who have been prescribed or use NSAIDS on a daily basis can continue using them but to promptly report mild fever or new myalgia.38Non-steroidal anti-inflammatory drugs remain the most controversial drug in the COVID crisis. Their analgesic effect is due to action on cyclo-oxygenase enzymes and causes peripheral inhibition of prostaglandin synthesis. Scientists believed that drugs such as ibuprofen could exacerbate the COVID-19 disease by upregulating the angiotensin-converting enzyme 2 (ACE2), which serves as an entry receptor for SARS-CoV-2.39 It is also proved to be an effective treatment for osteoarthritis of the knee and pelvis by improving the clinical condition and reducing pain. Platelet-rich plasma can be a better alternative to tendinopathy than steroid therapy. Platelet-rich plasma and bone marrow aspirate concentrate are among the orthobiologic therapies used as alternatives to current therapies for muscle, bone, and cartilage injuries.40 Further research on the aforementioned regenerative therapies seems necessary during the COVID-19 pandemic to find a good alternative to steroids and opioids.The body has an innate ability in treating its own pathology by repairing damaged tissue using autologous or allogeneic biologics. This ability is reinforced using regenerative medicine. There is variable evidence in favor of mesenchymal stem cells and platelet-rich plasma used in treating discogenic pain, radicular pain, facial joint pain, and sacroiliac joint pain.Precautions to Be Taken During In-Person Visit to Outpatient Department41  recommended a 3-tier approach for triaging all non-essential medical services and procedures by acuity: (1) low acuity or elective (postpone); (2) intermediate acuity or urgent (consider postponement); and (3) high acuity or emergent (do not postpone). Official Journal of the American Academy of Pain Medicine points out the following recommendations that are most applicable to interventional pain physicians:Place signs at triage points on appropriate hand hygiene, respiratory hygiene, and cough etiquette.Triage patients with fever and or respiratory symptoms and provide facemasks to symptomatic patients .Limit unnecessary patient escorts.Create an area for spatially separating patients ideally at least 6 feet apart in waiting rooms.Patients should be seen in a clean room, with no prior exposure to COVID-19 patients. If patients with COVID-19 or those suspected of having COVID-19 have been in the room, the room needs to be adequately disinfected. These patients should ideally be seen in a separate room.Hand hygiene should be performed with an alcohol-based hand rub for 15 seconds or with soap and water for at least 20 seconds before and between all patient care episodes.Strongly consider the use of surgical, procedural, or cloth face masks on patients during the interaction.In areas with community spread, providers can change into scrubs before seeing patients and out of scrubs before leaving the hospital.Avoid touching one’s face during exposures.Wear gloves during patient care and remove and discard gloves when leaving the care area and immediately perform hand hygiene.Health care providers can wear surgical masks for OPD interaction. N95 masks can be used for “high-risk patients.” Limited reuse of N95 is permissible during times of shortage. In such a scenario, cleanable face shields over the N95 mask should be used to reduce the chance of contamination.Clean and disinfect all surfaces in the patient care environment including tables, beds, chairs, door handles, and equipment between each patient encounter.In India, quarantine is being lifted in many parts of the country, despite the extensive community spread of coronavirus. The aforementioned precautions can be easily implemented inside the health care setup. Once in community spread, all patients must be considered “high risk.” Considering all patients to be asymptomatic COVID carriers, the number of patients seen per day can be limited. Based on the latest data, the brief contact, such as during a pain medicine consult, confers little risk of transmission from an asymptomatic carrier if precautions are not taken.42 stated that only specific urgent, semi-urgent procedures should be performed in designated rooms which should be properly disinfected later. The categorization of pain procedures as elective, urgent, and emergent is in many cases subjective. Though most procedures are characterized as elective, intrathecal pump (ITP) refills and malfunction, and neurostimulator infection and malfunction are considered “urgent.” Guidelines suggest avoiding the insertion of both new intrathecal pumps (except for highly selective cancer patients) and neurostimulators. Pre-encounter briefings, simulation sessions using telemedicine if needed, and the presence of an observer during the removal and discarding of protective gear are highly recommended. The American Society of Pain and Neuroscience COVID-19 Task Force endorses that if the locality or region has sufficient medical resources and personalized protective equipment (PPE) to handle current and/or near-term projected COVID-19 cases, clinicians can proceed with all urgent and urgent elective interventional pain procedures while employing proper social distancing, screening, and testing recommendations.43On March 27, ASRA and ESRA guidelinesSemi-urgent procedures are those involved to treat:intractable cancer pain,acute herpes zoster or sub-acute, intractable post-herpetic neuralgia,acute herniated disc and/or worsening lumbar radiculopathy,antractable trigeminal neuralgia,early complex regional pain syndrome,acute cluster headaches and other intractable headache conditions, andother intractable medically resistant pain syndromes (should be reviewed on a case-by-case basis).44 N95 masks should be used as recommended by the Centers for Disease Control and Prevention and ASA when procedures with the potential for aerosolization such as intranasal sphenopalatine ganglion blocks and intra-oral injections are performed.45 Only urgent or emergent cases should be performed for high-risk patients, as outlined above. These procedures should be conducted in a specially designated room . After the procedure, the patient should be monitored in the same room and then transferred to an appropriate isolation area or discharged home to shelter in place. The use of complete PPE with proper donning and doffing is advocated. Equipments like the ultrasound machine and ITP or programmer should be protected from contamination using an appropriate cover. In addition, it is important to ensure that necessary medications  and equipment are ready and transported in a fully covered plastic bag and handled with sterile gloves in a clean area. Radiofrequency ablation without prior diagnostic blocks and spinal cord stimulation can be allowed without a trial.On May 18, however, an interim guideline issued by WHO stating “the prior recommendation that all elective procedures be postponed” has been removed. Thus, more in-patient visits and in turn more interventions are likely to happen, and care must be taken to protect both HCW and patients. Preoperative screening followed by testing (if required) at least 48 hours prior to the procedure is suggested. Testing should be done in symptomatic patients, patients with a recent history of contact with COVID-19 patients, patients belonging to “hot spot” area, patients requiring procedure around the airway, and patients requiring general anaesthesia. Interventional pain procedures can be categorized based on 3 factors: percutaneous versus incisional/surgical procedure; short versus prolonged neuraxial entry; and aerosol-generating procedures versus non-aerosol-generating procedures. For the most common procedures performed, patients are positioned prone, and the contact area is limited and sterilely prepped. Most percutaneous interventional pain procedures are performed using a surgical cap, mask, and gloves, without a gown. Examples include ESIs and peripheral nerve blocks. When an individual is performing a percutaneous procedure with prolonged neuraxial access, such as spinal cord stimulation trial or kyphoplasty, it is recommended that a gown be used, in addition to the aforementioned barriers.Chronic pain plays a crucial role in an individual’s physical and psychosocial well-being, and access to pain management services is a fundamental human right. In the current scenario of the COVID-19 pandemic, the burden of chronic pain has increased manifold. Precautions at OPD and during interventional procedures are of the utmost importance to avoid healthcare setup from becoming nidus of infection. Washing/sanitizing hands in between checking 2 patients and maintaining standard hygiene cannot be emphasized enough. Mental health care should be given its due significance and should be sorted by both patients and pain physicians. Drug alterations should be done depending on risk–benefit ratio. Telemedicine should be exploited to provide OPD consultation, patient procedural education, and pre/post-procedural consultation.