Chronic pain, including chronic low back and leg pain are prominent causes of disability worldwide. While patient management aims to reduce pain and improve daily function, prescription of opioids remains widespread despite significant adverse effects. This study pooled data from two large prospective trials on 10 kHz spinal cord stimulation (10 kHz SCS) in subjects with chronic low back pain and/or leg pain and performed post hoc analysis on changes in opioid dosage 12 months post 10 kHz SCS treatment. Patient-reported back and leg pain using the visual analog scale (VAS) and opioid dose  were compared at 12 months post-10 kHz SCS therapy to baseline. Results showed that in the combined dataset, 39.3% of subjects were taking >90 MME dose of opioids at baseline compared to 23.0% at 12 months post-10 kHz SCS therapy (p = 0.007). The average dose of opioids in >90 MME group was significantly reduced by 46% following 10 kHz SCS therapy (p < 0.001), which was paralleled by significant pain relief (P < 0.001). In conclusion, current analysis demonstrates the benefits of 10 kHz SCS therapy and offers an evidence-based, non-pharmaceutical alternative to opioid therapy and/or an adjunctive therapy to facilitate opioid dose reduction whilst delivering significant pain relief. Healthcare providers involved in management of chronic non-cancer pain can include reduction or elimination of opioid use as part of treatment plan when contemplating 10 kHz SCS. While acute pain is generally nociceptive pain associated with somatosensory stimuli, chronic pain is thought to involve a shift from peripheral damage to more prominent central sensitization and central nervous system mechanisms2. In general, the worldwide prevalence of chronic pain in developed nations is around 20% and can be grouped into seven etiologies: primary pain that is not explained by another pain condition, cancer pain, neuropathic pain, posttraumatic and postsurgical pain, musculoskeletal pain, visceral pain and headache and orofacial pain7. Chronic low back pain (CLBP) is one of the most prevalent types of chronic pain; it is the leading global cause of disability, one of the common reasons for visits to physician’s office, correlates with work absence and is therefore associated with significant economic costs13.Chronic pain, defined as pain that remains beyond normal healing time, is a debilitating group of conditions and a prominent cause of disability worldwide14. Of these, opioids are amongst the most commonly prescribed drugs for low back pain15, yet their use remains controversial16. Limited head-to-head evidence suggests opioids to be more effective than naproxen or placebo for relieving CLBP18, but the average effect is little more than a 10-mm reduction on a 100-mm visual analog scale (VAS), a decrease that is not considered to be clinically meaningful20. In addition, opioids have well-described short and long-term side effects such as constipation, nausea, vomiting, sedation, dizziness, respiratory depression, hormonal imbalance, changes in immune response and physical dependence; opioid overdose deaths are mainly due to acute respiratory depression caused by opioids23. Moreover, opioid use for chronic pain conditions like CLBP can cause tolerance, hyperalgesia, misuse, abuse and diversion27. Therefore, international guidelines agree that opioids need to be cautiously prescribed and should be discontinued if the benefits do not outweigh risks28.Management of CLBP, like other chronic pain conditions, aims to reduce pain and improve daily function. If non-pharmacological options such as bed rest, superficial heat, cryotherapy, exercise and physiotherapy are unsuccessful, pharmacological therapies are a second-line option29. Even at doses ≥50 MME/day, the risk of death from opioid overdose is doubled30. The challenge for patients and prescribers is for patients taking ≥90 MME/day, the CDC recommends other approaches to pain management and a taper and discontinue approach for the opioid29. However, no definite alternatives are recommended.In 2016, the Centers for Disease Control and Prevention (CDC) published guidelines on using opioids for management of chronic pain and capped the maximum opioid dose at 90 milligrams morphine equivalent (MME)/day as the risk of abuse and misuse rises with higher doses31. With SCS, the painful region is stimulated using electrical pulses and the transmission of abnormal pain signals to the brain is altered31. Stimulation is generally provided through electrode arrays placed into the epidural space percutaneously, or through a surgical paddle lead delivered via a laminotomy. First generation SCS devices generally deliver pulse frequencies between 40 to 60 Hz with the intent of replacing the pain sensation with a stimulation-produced sensation known as paresthesia32. However, it is challenging to produce reliable and tolerable paresthesis in the axial back region33. For this reason, it’s use has been largely limited to leg pain. Moreover, some patients report paresthesia as an unpleasant sensation34 and the perceived intensity of paresthesia can increase with body movement35. Another challenge of previous devices and new iterations of these devices is providing durable pain relief for back and leg pain. Multiple studies demonstrated that approximately 50% of the patients achieve ≥50% pain relief with traditional SCS and even in the patients who respond initially, therapy effectiveness was found to diminish with time44.Therefore, for improved quality of life, patients may desire and benefit from a reduction in opioid usage just as much as they seek relief from chronic pain through additional treatment options that enable them to achieve both goals. A minimally invasive alternative to opioid therapy is spinal cord stimulation (SCS), a type of neuromodulation typically used to treat chronic intractable neuropathic pain conditions like failed back surgery syndrome (FBSS)47. Its use has been approved for patients with chronic refractory pain of the trunk and/or limbs and is particularly suitable for CLBP.49. Two studies described previously (SENZA-EU and SENZA-RCT) showed 10 kHz SCS therapy relieves low back pain and leg pain for up to 24 months post-implant51. Compared to traditional SCS, 10 kHz SCS demonstrated superior pain relief as well as long-term improvement in quality of life in subjects with leg pain and/or CLBP52.More recently, SCS has evolved into a variety of different modalities. One of these is 10 kHz SCS therapy that applies a 10,000 Hz waveform and provides paresthesia-free pain relief53. Prospective studies have shown that traditional SCS can reduce reliance on medication for management of pain. In a randomized controlled trial, North et al. reported that 87% (20/23) of FBSS patients in the SCS group were either stably using opioids or decreased their opioid use and only 13% (3/23) patients needed to increase their use of opioids whereas 58% (15/26) patients had a stable or decreased opioid use and 42% (11/26) patients required increased opioid use in reoperation group37. The results were further supported by systematic reviews on safety and efficacy of SCS for chronic pain including CLBP and FBSS, which reported stable or reduced medication usage in 65% and 53% patients treated with SCS respectively54. However, the definition of medication included opioid as well as non-opioid drugs in both studies and so far, to our knowledge, no chronic pain SCS study has assessed reduction in opioid dose as the primary endpoint and none have explored the ≥90 MME high-risk category.Despite their increasing use, to date there has been limited investigation on the role of SCS in facilitating a reduction or elimination of opioids in chronic pain managementThis post hoc analysis of the SENZA-EU and SENZA-RCT studies examines the effect of 10 kHz SCS therapy on opioid analgesic pain management in the ≥90 MME high-risk category for subjects with leg pain and/or low back pain. This analysis will determine if 10 kHz SCS therapy may facilitate successful reduction of opioids in subjects taking the ≥90 MME doses for management of chronic pain in routine clinical practice.In SENZA-RCT, 89 subjects were successfully included through 12 months and in SENZA-EU, 68 subjects were included through 12 months. Out of the subjects with pain relief data, 83 subjects in SENZA-RCT and 54 subjects in SENZA-EU (137 subjects in the combined population) had opioid usage data at baseline or 12-month assessment. They were included in initial analyses of demographics and clinical characteristics.As listed in Tables Further analyses on mean opioid reduction, reduction in pain intensity scores and classification of subjects based on opioid dose were carried out in subjects with information on opioid dose. At baseline, dose information was available in 75 subjects in SENZA-RCT, 54 subjects in SENZA-EU and 129 subjects in the combined dataset  across both back and leg pain  are shown in Table Figure Subjects taking >90 MME of opioids at baseline were then studied further for changes in opioid dose following 10 kHz SCS therapy. At baseline, 36 subjects in SENZA-RCT, 15 subjects in SENZA-EU and 51 subjects in the combined dataset were taking >90 MME of opioids for management of pain Fig. . Twelve For subjects on high doses of opioids prior to treatment (>90 MME), in the combined dataset, 12 months post-10 kHz SCS therapy resulted in a 45.9% reduction in the mean opioid dose at follow-up from 196.8 ± 14.2 to 106.5 ± 14.1  from one doctor, and of those who overdosed, 40% were also prescribed their pain relief from a single doctor29. Surveys have reported that 70% of long-term opioid users suffer from a chronic disease or disability which limits their daily function60. Assuming 10% of these patients may be on high-doses to maintain an adequate level of function and pain relief, feasible alternative options are required to reduce the risk of overdose. Clearly, patients suffering from CLBP and leg pain need evidence-based, safe and effective alternatives to long term opioid therapy.Despite clear guidance on maximum doses of opioids and the rationale for high-dose opioids becoming weaker, patients continue to rely on doses > 90 MME for pain management. A recent retrospective analysis of 1,066 primary health care records of patients prescribed opioids for chronic non-cancer pain, 9.7% were receiving ≥90 MMEIn the current study, patients had CLBP and leg pain for an average of 11.3 ±0.8 years. They experienced significant baseline pain, despite being managed by prescription opioid therapy. Over a third (39.3%) of subjects were taking > 90 MME of opioids at baseline. 10 kHz SCS therapy was successful in reducing the mean opioid dose and patient reported pain at 12 months. Figure Not only was 10 kHz SCS therapy able to reduce the overall dose of opioids used by subjects with CLBP and leg pain, it reduced the proportion of subjects requiring high-risk doses >90 MME per day at the same time. Figure s in opioid dose and higher proportion of subjects taking lower doses of opioids at 12 months were observed in the SENZA-EU study. There may be multiple factors contributing to these observed differences. While SENZA-EU was a prospective, single-arm study designed to assess the efficacy of 10 kHz SCS system, SENZA-RCT was a randomized controlled trial designed to compare 10 kHz SCS with traditional SCS in order to support regulatory approval. Thus, the SENZA-RCT was highly focused on pain management rather than opioid reduction, whereas more emphasis was placed on weaning SENZA-EU subjects off of opioids. In SENZA-RCT, subjects were allowed to continue on stable doses of opioids but were considered as treatment failures regardless of pain scores (VAS) if they increased opioid dose. Related, there were also differences in pain management practice between study centers in SENZA-EU and SENZA-RCT. Investigators from SENZA-EU study actively encouraged the subjects to titrate and taper their opioid dose, whereas investigators from SENZA-RCT did not actively encourage opioid reduction. Lastly, chronic pain patients who are on long term opioids but still have high pain scores underscores the observation that opioids seem to have little benefit in improving chronic pain, especially as measured by VAS, yet are difficult to discontinue. Over the past decade, especially in the US, patients remained on opioids despite their dubious clinical benefit. This may have translated into clinical management changes that were not part of the goals of the RCT or EU studies.Interestingly, compared to SENZA-RCT, higher reduction67. The CDC guidelines published in 2016, recommended caution when increasing the opioid doses above 50 MME and avoiding opioid doses above 90 MME29. To prescribe safe doses of opioids and to wean the chronic pain patients off opioids, pain management specialists need durable alternatives for management of chronic pain. The current findings indicate that 10 kHz SCS can be considered as an alternative to opioids. A case-controlled retrospective study by researchers from Boston, USA showed that opioid usage was reduced or eliminated in 71% (n = 15/21) of patients treated with 10 kHz SCS for back and/or leg pain68. Another retrospective study by pain management specialist from Perth, Australia showed that percentage of patients not taking opioids increased nearly 2-fold in patients treated with 10 kHz SCS therapy and 70% of patients either eliminated or reduced their opioid dose at last follow-up. More importantly, average opioid dose in patients taking high dose opioids at baseline was reduced by 47% at last follow-up69. Current study further confirms the findings from the retrospective studies and shows that 10 kHz SCS can provide long-lasting pain relief and allow reduction or elimination of opioids even in patients who were prescribed high-risk doses. Pain physicians need to take note of the findings from the studies and encourage patients treated with 10 kHz SCS to discontinue opioids. They need to include reduction or elimination of opioid use as part of treatment plan when contemplating 10 kHz SCS. Establishing opioid reduction as part of the treatment goal even prior to the trial could help in setting up expectations and result in meaningful improvement in quality of life.In the past few years, several studies have documented lack of clinically relevant efficacy with the use of opioids for chronic non-cancer pain and highlighted the harmful side effects of using opioidsThe main limitation of this study is that it involved post hoc analysis of the dataset and there was no prospectively defined statistical analysis plan (SAP) for predetermined outcomes. Although the combined dataset in the study included 129 subjects with opioid dose information, there were differences between the two studies and the number of subjects taking > 90 MME was relatively small. Additional prospective studies and real-world studies may be needed to validate the findings of this analysis. Nevertheless, current analysis shows that despite the differences between the two studies and the patient cohorts, 10 kHz SCS therapy resulted in significant reduction in opioid dosage while maintaining pain relief when the data was analysed individually and when combined.Based on the results of this study, 10 kHz SCS therapy has the potential to assist physicians and patients in the wake of the opioid crisis, offering a non-pharmacological alternative to the suite of pain management tools for patients on high-risk doses of opioids (>90 MME).50. The study protocol and informed consent forms were approved by each study site’s ethic committee . Local clinical research and data protection regulations, good clinical practice guidelines (ISO 14155), and the Declaration of Helsinki were followed during the study. Selection bias in the study was minimized by the involvement of independent medical monitors, which assured high level diligence for the recruitment of subjects. Inclusion and exclusion criteria for enrollment of patients has been previously reported50. Briefly, patients who signed informed consent forms, with chronic back pain  with or without leg pain with pain intensity of ≥5.0 cm (average score over the last 30 days) on the 0 to 10 cm, visual analog scale (VAS), who were ≥18 years of age and who were candidates for SCS were included in the study. Patients were evaluated at baseline and then received a trial 10 kHz SCS  therapy for 14–30 days50. Patients who had at least 50% reduction in pain intensity received a permanent IPG implant and followed for 24 months with assessments at 1, 3, 6, 12, and 24 months50. Subjects were enrolled in the study between August 2009 and February 2011. The follow-up for the last implanted patient was completed in April 2013. The study design allowed adjustment of stimulation parameters and clinical judgement-based adjustment to pain medication dosage throughout the follow-up period50.As described previously, SENZA-EU was a prospective, multicentre, open-label study in 83 subjects conducted at two European centers including AZ Nikolaas Pain Centre, St Niklaas Belgium and Guy’s and St Thomas’ Pain and Neuromodulation Centre, London, United Kingdom51. The study was conducted in compliance with the U.S. Code of Federal Regulations and recommendations guiding physicians in biomedical research by the 18th World Medical Assembly, Helsinki, Finland. The study protocol and informed consent forms were approved by each study site’s institutional review board . Selection bias in the study was addressed by the involvement of independent medical monitors for the recruitment of subjects and randomized assignment of subjects to the 10 kHz SCS group. Patients who signed informed consent forms and were candidates for SCS with chronic, intractable back and/or leg pain, refractory to conservative therapy for a minimum of 3 months with an average back pain intensity of 5 or greater out of 10 cm on the VAS, average leg pain intensity of 5 or greater out of 10 cm on the VAS, an Oswestry Disability Index (ODI) score of 41 to 80 out of 100 were randomized in a 1:1 ratio to receive stimulation with an investigational 10 kHz SCS therapy system  or a commercially available SCS system 51. Patients underwent a percutaneous trial lasting up to 14 days51. Those with ≥40% back pain reduction from baseline proceeded to permanent implantation and subjects with at least 50% pain reduction were considered as ‘responders’51. Subjects were enrolled between June 2012 and December 2012. Following randomization, subjects were implanted with 10 kHz SCS system and followed through 12 months, which concluded in February 2014. Oral analgesics were stabilized from 28 days before enrollment until activation of the implanted SCS system, excluding allowances for perioperative analgesics51. Adjustments were then allowed under the guidance of a study investigator as medically necessary, but the subjects who increased their opioid dose were considered as ‘non-responders’ regardless of their pain relief51. Assessments were performed at scheduled visits 51. Data from subjects implanted with 10 kHz SCS system was included in the current analysis.SENZA-RCT was a prospective, randomized, controlled trial in 198 patients across 10 centers in the U.S., designed to assess 10 kHz SCS therapy as compared with traditional low frequency SCSBoth studies, SENZA-RCT and SENZA-EU assessed back and leg pain intensity as patient reported VAS  at baseline and 12 months. Opioid medication dose was assessed in both studies at baseline and 12 months as  and the changes in opioid consumption were recorded as “eliminated”, “decreased”, “no change” or “increased”. The assessments were comparable between the studies and therefore it was possible to combine the data from the studies.Demographic analyses were performed in the implanted patients with data at 12 months and with basic information on opioid usage (Fig.


Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established treatment for patients suffering from trigeminal neuralgia (TN) as a primary modality or for those refractory to medical treatment. However, few existing studies have identified intraoperative parameter or navigation technique that can be used to predict the rates of short-term or long-term pain relief. In this study, we analyzed patient characteristics, intraoperative parameters and technical factors, and postoperative changes in relation to immediate and long-term pain relief.This study included a total 252 patients in which 340 RF-TR were performed under the guidance of intraoperative computed tomography (iCT) alone or with magnetic resonance image (MRI) and iCT fusion imaging.The immediate pain relief of RF-TR with iCT alone and iCT with MR image guidance with or without cerebrospinal fluid (CSF) outflow were all above 90.4%. The 2-year pain relief rate of RF-TR using iCT alone and iCT with MR images guidance with or without CSF outflow were 47.8%, 39.8%, 71.7%, and 53.9% respectively. Significant factors for 2-year pain relief were CSF outflow, iCT with MR image fusion, non-recurrent TN, and presence of postoperative facial numbness.This preliminary study demonstrated foramen ovale cannulation under the aid of iCT with MR image guidance could improve 2-year pain relief. Percutaneous radiofrequency trigeminal rhizotomy (RF-TR) is a well-established and effective technique for treating trigeminal neuralgia (TN) . The shoRF-TR is usually done under the guidance of fluoroscopy; however, computed tomographic or navigation assistance can be employed for added safety and precision, especially for the less experienced surgeon. RF-TR with intraoperative computed tomography (iCT) navigation became the treatment of choice in our center since August 2010, which progressed further to include fusion images of computed tomography and magnetic resonance image (MRI); this progression was based on the fact that prior image guidance techniques only allowed the accurate cannulation of the foramen ovale, whereas the inclusion of MRI enabled visualization of the trigeminal cistern and ganglion, which we hypothesize could facilitate better anatomical localization of the target for lesioning. We have shown that this technique can shorten the procedure time and is easy to master, and although short-term pain relief is demonstrated, the long-term advantage of the added image assistance remains unknown , 17. In Two hundred fifty-two consecutive patients, who were diagnosed with medically refractory TN and received RF-TR under iCT navigation at Chiayi Chang Gung Memorial Hospital, were enrolled from May 2010 to February 2016. Two hundred thirty patients had classical TN; 18 had tumor with nerve compression, and 4 had post-herpetic neuralgia. Of the patients, 162 (64.3%) were women and 90 (35.7%) were men. The patient’s age ranged from 20 to 90 years . Other clinical characteristics are shown in Table All procedures were performed on an outpatient basis at our Brain-SUITE® iCT. The MRI series were taken at the outpatient department before the procedure, and the CT images were acquired intraoperatively before cannulation of the foramen ovale. The trigeminal cistern was marked on all axes of the MRI slices, and the foramen ovale and the lateral pterygoid plate were highlighted on all axial slices of CT images. The MRI were fused with the CT images on the iPlan® 2.0 platform with Cranial Essential & Unlimited® 1.0 software .The patient was placed in supine position with their head in slight extension on a snug-fitting horseshoe headrest. The hub of the needle was attached to the instrument adaptor, and the foramen ovale was cannulated based on the Hartel’s technique with adjustments by fusion image guidance. The target of the needle tip was 6 mm beyond the endocranial surface of foramen ovale based on the CT image guidance without MRI fusion; by contrast, the needle tip was placed into the trigeminal cistern based on MRI fusion guidance Fig. . The locTwo hundred fifty-two patients were followed up for 2–8 years via subsequent outpatient visits or a phone interview. A numeric rating scale (NRS) score was used to evaluate the severity of pain before and after the procedure. The NRS, the interval to recurrence and facial numbness (included different degrees of hypoesthesia and dysthesia), as well as the occurrence of postoperative complications such as anesthesia dolorosa, diplopia, keratitis, and masseter weakness were recorded during serial follow-up.U test and chi-square test. The clinical outcome in relation to ablation temperature, CSF outflow, and complications (odds ratios [ORs]) were analyzed by univariate binary logistic regression analysis. All factors with a p value < 0.2 by univariate analysis were considered in the multivariate model using a backward elimination strategy. A p value < 0.05 was considered statistically significance. Missing data were censored in all analyses. All data analyses were performed with the Statistical Product and Service Solutions (SPSS) version 23.0.The patients were grouped according to the type of image guidance used ; the patient and procedural characteristics were compared using the Mann-Whitney Comparison of the patient groups using iCT alone and iCT with MRI fusion is shown in Table The procedure characteristics according to various outcome groups are listed in Table On univariate analysis of the patient characteristics, intraoperative parameters, and postoperative changes, immediate pain relief was related to CSF outflow, iCT with MRI guidance and postoperative facial numbness, and negatively correlated to neuralgia involving the V1 dermatome; in a multivariate model, postoperative facial numbness and involvement of V1 distribution remained statistically significant Table . The faiSignificant factors for pain relief lasting more than 2 years on univariate analysis were younger age, CSF outflow, iCT with MRI guidance, non-recurrent TN, postoperative numbness, and involvement of the V2 dermatome. CSF outflow, iCT with MRI guidance, non-recurrent TN, and postoperative facial numbness remained statistically significant in a multivariate model Table .Table 5RThe immediate pain relief rate following repeated RF-TR for patients suffering from recurrent TN was 97.5%, which was comparable to non-recurrent cases receiving their first RF-TR; however, the rate of recurrence in this patient group was 43.6% at 2 years. On univariate analysis, significant factors for 2-year pain relief in the group of recurrent TN were younger age, involvement of V2 distribution, CSF outflow, iCT with MRI guidance, and postoperative facial numbness; however, no factors remained statistically significant in a multivariate model (Table One hundred eight patients (31.8%) had postoperative facial numbness after RF-TR; the percentage of postoperative facial numbness was lowest in patients that had no pain relief after RF-TR (4.5%) and highest in those that had a durable response for more than 2 years (46%). There were 13 patients (3.8%) who complained of severe dysesthesia and anesthesia dolorosa developed in 6 patients (1.8%). Masseter weakness was observed in 49 (14.4%) of 340 procedures and these patients reported no disability, and the weakness improved gradually. No patient suffered from oral cavity penetration, diplopia, corneal keratitis, CSF leakage, carotid-cavernous fistula, oculomotor nerve palsy, or abducens nerve palsy. The complications had no correlation with the ablation temperature, CSF outflow, or previous treatment modality.Neuronavigation is a widely adopted technology in modern neurosurgery , 35, 36.The occurrence of CSF outflow during cannulation was sixfold higher when MRI fusion was used compared to iCT alone, which was also associated with a better 2-year outcome. This can be due to the fact that CSF may act as an effective conductive medium for heat transfer by convection around the gasserian ganglion within the trigeminal cistern, and that CSF may prevent tissue charring around the needle tip for an effective lesioning volume , 21. WhiThe common complications after RF-TR are severe dysesthesia 3.7–25%), anesthesia dolorosa (0.5–2%), and masseter weakness 4.1–30%). The less common complications are keratitis (0.4–4%), diplopia , CSF leak 0.16%), meningitis (0.2%), carotid- cavernous fistula (0.06–0.14%), and blindness –30%. The, 32, 34.%, anesth%, meningTreatment of TN with isolated or concomitant V1 involvement by RF-TR is controversial , 38; theRecurrent TN was found to be a poor prognostic factor in subsequent RF-TR, as more than half suffered from relapsing pain in spite of initial pain relief following repeated RF-TR; however, outcome predictors for RF-TR in patients with recurrent TN could not be identified. The pathophysiological mechanism of recurrent TN is not well understood; it could be related to sparing of the trigger myelinated A-beta fibers by radiofrequency rhizotomy, which selectively destroys A-delta and C fibers , and theThe voltage threshold for pain reproduction on test stimulation was not predictive of the outcome, whereas other technical factors such as the use of iCT guidance with MRI fusion and the occurrence of CSF outflow were favorable prognostic factors, thus a shift in needle targeting from electrophysiological-based stimulation to image-based anatomical localization could have the potential to eliminate the ambiguity in pain reproduction of test stimulation, and enables a greater degree of patient comfort from a deeper level of sedation during the procedure.The present study demonstrated that accurate anatomical localization by the use of the iCT with MRI fusion could avoid all puncture-related complications to result in a good outcome at 2 years, and CSF outflow using this technique is a favorable predictor for long-term pain relief.


Adequate control of acute postoperative pain is crucial in breast surgeries, as it is a significant factor in the development of persistent chronic pain. Inadequate postoperative pain control increases length of hospital stays and risk of severe complications. Erector spinae plane block (ESPB) is a novel regional block that has the ability to sufficiently block unilateral multidermatomal sensation from T1 to L3. By reviewing the literature on ESPB, this paper aimed to elucidate its efficacy in breast surgery analgesia and its role in addressing the opioid crisis in North America.PUBMED, EMBASE, and Cochrane databases were systematically searched for relevant articles according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inclusion criteria included any articles that described ESPB in breast surgery. Exclusion criteria composed of articles that exclusively discussed other kinds of regional blocks.Thirty-two articles including 6 randomized controlled trials were included in this review. ESPB demonstrated superior pain control and less opioid consumption compared with tumescent anesthesia or using no block. However, ESPB showed lower efficacy in pain control compared with pectoral nerve block. Patients experienced less nausea and vomiting and were overall more satisfied with ESPB compared with other pain control modalities. The vast majority of the studies reported the ease of ESPB administration, and only 1 case presented with a complication.ESPB is a promising form of regional anesthesia that can decrease postoperative pain and opioid consumption when used as part of multimodal pain analgesia for patients undergoing breast surgery. One common feature they share is the significant postoperative pain experienced by patients, with some studies showing that over 50% of patients undergoing mastectomy and reconstruction experience pain up to 1 year postoperatively.13 The opioid epidemic has fueled continuous efforts in improving pain management in plastic surgery procedures and specifically breast surgery.15 A case–control study of almost half a million individuals who underwent plastic or reconstructive surgery found that patients undergoing breast surgeries are the most susceptible to both acute and prolonged postoperative pain.16 Although many patients prefer tolerating pain rather than overconsuming opioids, the literature shows that breast surgeons usually overprescribe them.18 Therefore, it is the physician’s responsibility to seek benign pain control modalities to ease patients’ recovery and fight the opioid epidemic.The past few decades have witnessed a surge in opioid consumption as a method of postoperative analgesia. Alarmingly, levels of addiction and opioid-related mortality have reached over 42,000 deaths annually in the United States alone.20 This change parallels the surge in interest for quality improvement initiatives and Enhanced Recovery after Surgery pathways in hospitals to improve outcomes and increase patient satisfaction. A recent meta-analysis demonstrated superior pain control with regional blocks compared with opioid-based analgesia.20 In addition, they allow for earlier patient mobilization, faster return to function, and carry no risk of addiction and overdose.21Although using regional blocks as an adjunct form of analgesia existed for many years, they have only recently increased in popularity as a method of postoperative pain management.22 Several regional nerve blocks have been proposed for breast analgesia.23 Popular examples include the pectoral nerve blocks (PECS I and II) and paravertebral blocks (PVBs).24 Although the efficacy of these blocks has been well demonstrated, they all incur limitations, such as increased hematoma rates, risk of pleural punctures, and intravascular injections.27 Furthermore, the spread of local anesthetic through the fascial planes in PECS can prevent the electrocautery from functioning at an acceptable level.28 A recent systematic review of fascial plane blocks in breast surgeries showed that none of the reviewed blocks provide complete analgesia to the whole breast region alone.21In surgeries for breast cancer specifically, there is further evidence that regional anesthesia attenuates the surgical response system and can reduce the progression of malignancy.29 It demonstrated the ability to sufficiently anesthetize unilateral multidermatomal sensation from T1 to L3 when administered at T5.30 When compared with the commonly used PVB in thoracotomies, ESPB showed similar pain relief results with less adverse effects.31 In the past 2 years, ESPB has been used in several breast surgeries, such as mastectomies and breast reconstruction.33 Although several systematic reviews summarize the efficacy and limitations of interfascial regional blocks, none have been conducted for ESPB in breast-related surgeries.The erector spinae plane block (ESPB) is a novel regional anesthesia technique first described by Forero et al in 2016 as a successful interfascial block for neuropathic pain in the thorax.The goal of this study is to systematically review the literature on the efficacy of ESPB in breast surgeries, specifically, mastectomies, lumpectomies, breast augmentations, reductions, and reconstructions. By reviewing the literature, this paper aims to elucidate ESPB’s efficacy in breast surgery analgesia, and its potential role in addressing the opioid crisis in North America. It is hoped that this will encourage surgeons to comfortably prescribe less opioids and provide an alternative, safer pain management method for patients.The PUBMED, EMBASE, and Cochrane databases were systematically searched for relevant articles using both keywords and MeSH terms. The specific search strategy used for PUBMED was the following: (“mastectomy” OR “lobectomy” OR “breast” OR “Breast”[Mesh] OR “reduction” OR “augmentation” OR “reconstruction”) AND (“erector”). Similar searches were conducted on the 2 other databases.This systematic review was performed and reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Two authors independently reviewed all resulting search entries against the inclusion and exclusion criteria. Any disagreement over the eligibility of an article was adjudicated by an independent researcher. Inclusion criteria consisted of studies that described ESPB in adult females (>18 years) undergoing breast surgery. Due to the novelty of this technique, randomized controlled trials (RCTs), prospective studies, case control studies, and case series/reports were included. Furthermore, there was no lower limit on the number of cases within a study for it to be included. Exclusion criteria composed of articles that exclusively discussed other kinds of regional blocks, and those that discussed ESPB in nonbreast-related surgeries. Finally, commentaries and conference abstracts were excluded.52 Out of the 32 articles, 6 were RCTs54 and 26 were case reports and case series. All of the articles were published between June 2017 and May 2019 ,57 5 discussed ESPB combined with another method of regional anesthesia , and 1 discussed ESPB with the addition of a local anesthetic .43 In total, the case reports and case series comprised 60 patients of ages 20–83 years. The reporting of outcomes was heterogeneous among the RCTs and the case reports/series. The most common measured outcome was postoperative opioid consumption (n = 23) followed by postoperative pain (n = 22).Out of 26 case reports/series, 21 articles discussed the exclusive use of ESPB (continuous and noncontinuous),P < 0.05).54 A higher concentration of bupivacaine was associated with less postoperative opioid consumption needed (P = 0.03).51 Furthermore, ESPB was found to significantly decrease opioid consumption within the first 24 hours post breast reduction when compared with tumescent anesthesia (P < 0.05).45 However, both Altiparmak et al and Gad et al showed that patients undergoing unilateral mastectomies who received an ESPB required significantly more tramadol and morphine compared with patients who received a PECS block .53 However, it is important to note that both articles used more local anesthetic in the PECS block versus the ESPB (30 cc versus 20 cc) , it is challenging to quantitatively compare postoperative opioid consumption in the different case series.P < 0.05),54 whereas the other RCT evidenced no differences in pain between the patients who received ESPB and those who received no regional anesthesia.40 Furthermore, Oksuz et al found that patients undergoing ESPB had significantly less postoperative pain compared with tumescent anesthesia (P < 0.0001).45 The RCT comparing different concentration of bupivacaine in ESPB showed that patients who received the higher concentration of 0.375% had significantly less pain levels at every measured time point (P < 0.05).51 Finally, the 2 RCTs that compared ESPB with a PECS block found that patients undergoing the former block had higher levels of pain in the first 24 hours postoperatively (P < 0.05).53 Pain scores were further mentioned in 16 case reports, most of which (15 out of 16) reported the mean pain scores to be less than 5 on the VAS or NRS during the first 24 hours postoperatively. The maximum pain score reported by 1 patient was 6.43 Postoperative rescue analgesia was provided to patients with an NRS of 4 or higher.Pain level was measured using either an NRS or a VAS in all 6 RCTs. When compared with no regional anesthesia (only GA), only 1 RCT found that patients who underwent an ESPB had significantly lower levels of pain at 0, 2, and 4 hours postoperatively (P < 0.005).45 Although there was no significant difference between patients who received ESPB and those who received no regional anesthesia (P = 0.768) in 1 of the studies,40 another showed that 5 of 20 control patients in comparison with none of the ESPB patients required rescue metoclopramide for severe PONV.54 Furthermore, a higher concentration of bupivacaine was not shown to affect PONV, as demonstrated by Altiparmak et al51 One case series on 2 patients measured PONV and simply stated that no PONV was observed.59Symptoms of nausea and vomiting were measured in 4 of the 6 RCTs. Patients who received ESPB were found to have significantly less complaints of postoperative symptoms of nausea/vomiting (PONV) when compared with those who received tumescent anesthesia (P = 0.289).51 Furthermore, Gad et al found that there was no difference in the mean intraoperative fentanyl requirements between patients who underwent an ESPB compared with a PECS.53 Only 5 case series/reports discussed the use of intraoperative opioid requirement for pain response.46 Talawar et al found that 6 of 10 patients receiving ESPB required additional intraoperative fentanyl.46 Two other case reports mentioned the use of 15058 and 100 μg60 of fentanyl intraoperatively. On the other hand, Altiparmak et al and Kim et al reported that no additional intraoperative opioids were required for patients on ESPB.61Intraoperative opioid requirement due to pain response was measured in 2 of the 6 RCTs. The mean fentanyl requirement was found to be similar in both groups that were administered ESPB with different bupivacaine concentrations , and the tumescent anesthesia group (P < 0.001). Furthermore, 1 of the case reports mentioned patient satisfaction by stating that the patient was overall satisfied with the block. The case report failed to mention what test was used to measure satisfaction.61 The lengths of hospital stay of only 4 patients were reported, all of which varied between 8 hours and 3 days. However, due to the heterogeneity of the breast surgeries performed, no meaningful conclusion about length of hospital stay associated with ESPB should be drawn.61 Only 1 case report measured patient sleep quality and mentioned no postoperative insomnia.50 Prolactin and cortisol levels were measured in only 1 RCT which found no difference in either levels between patients who underwent ESPB and those who underwent a PECS block. However, both groups evidenced a significant decrease in both hormones 24 hours postoperatively.53The other outcomes reported include patient satisfaction, hospital length of stay, quality of sleep, and cortisol and prolactin levels. Two RCTs reported patient satisfaction.48 Only 1 major complication was recorded in a patient with a pneumothorax 3 minutes after the administration of ESPB.62Only 2 articles  reported complications. Ueshima and Otake reported 2 cases where there was inadequate intraoperative analgesic effect of the ESBP on T2–T6 intercostal nerves when assessed 20-minute postblock administration.45 Although PECS block was superior to ESPB block in terms of postoperative pain and opioid consumption, the authors of this review believe that ESPB is still a suitable option for breast surgeries especially due to the ease and safety of administration and the higher risk of complications associated with PECS blocks.53The present systematic review elucidates the potential benefits of ESPB in breast surgeries. All of the RCTs demonstrated positive efficacy of ESPB. As an adjunct to general anesthesia, it is found to be superior in decreasing postoperative pain and opioid consumption in patients undergoing mastectomies. When compared with tumescent anesthesia, ESPB was associated with less postoperative pain, opioid consumption, and overall greater patient satisfaction post breast reduction.29 Ueshima and Otake showed that the block still provided adequate breast analgesia when administrated in the lateral decubitus position, which allows the patient to be under general anesthesia before administration of the block.49 Aygun et al further demonstrated successful administration of ESPB via the “Dry Leaf technique” that allows the patient to be in the supine position. This permits administration of the block after commencement of the surgery.63 All 32 articles included in this review performed ESPB as described by Forero et al, but with slight modifications to the technique regarding position of patient , spine level of injection (T2–T5), and local anesthetic used , the authors of this study decided to include case reports/series to more accurately report the benefits of ESPB in these patient populations.Future studies should aim to investigate the variables that impact the spread of ESPB, such as patient position, age, and body habitus. In addition, future studies should aim to confirm whether ESPB provides adequate analgesia to the whole breast region via pinprick sensation testing. Furthermore, more RCTs should be conducted to verify the efficacy of ESPB compared with other widely used regional blocks, such as PVB and serratus anterior block. Future studies should also conduct cost–benefit analyses of ESPB which would provide great incentive in setting guidelines for breast perioperative pain control. Finally, none of the reviewed studies measure long-term opioid use.23 The ESPB is a promising form of regional anesthesia that can decrease postoperative pain and opioid consumption when used as part of multimodal pain analgesia. The technique is easy to perform under ultrasound guidance with a very low rate of complications.Given the prevalence of breast surgery, its risk for chronic postoperative pain, and the prolonged postoperative opioid use, there is growing interest for improved perioperative pain control using regional anesthesia.


Prognosis of medically treated trigeminal neuralgia patients is assumed to be poor, but the evidence is lacking. Thus, prospective real-life studies of medical management of trigeminal neuralgia are warranted.This was an observational study. Patients were consecutively enrolled in a structured management program at a specialist centre for facial pain. Optimisation of medical treatment, physiotherapy, psychotherapy, and advice from trained nurses, were parts of the program. Medically intractable patients were referred for neurosurgery. Data-collection was prospective using standardised schemes and patient surveys. The aim was to describe the two-year outcome of medical treatment at the specialist centre. The primary outcome was a 50% reduction in the overall burden of pain according to a Numerical Rating Scale (NRS) after two years.p < 0.01. There was no significant association between primary outcome and sex, depression and/or anxiety, concomitant persistent pain, or neurovascular contact with morphological changes of the trigeminal nerve.A total of 186 primary TN patients were enrolled in the program of which 103 patients remained medically managed and completed the two-year follow-up. Fifty patients were treated surgically within the first two years of follow-up. Half of the medically managed patients (53 (51%)), had more than a 50% reduction in the overall burden of pain over the two-year period. The overall burden of pain on NRS decreased from mean 5.34 to 3.00, Patients with trigeminal neuralgia improve over a two-year period when enrolled in a structured medical management program. Optimisation of drug treatment, continuous advice and education and support by the multidisciplinary team, referral of the medically intractable patients for surgery or the natural history of the disease, can be some of the reasons for the improvement. The favourable prognosis provides hope and optimism for medically managed TN patients.NCT03838393.Current study was observational, and patients were offered standard clinical care and laboratory workups according to current American Academy of Neurology and European Federation of Neurological Societies treatment guidelines. The study has been registered at ClincalTrials.gov. ID: The online version of this article (10.1186/s10194-019-0973-4) contains supplementary material, which is available to authorized users. Trigeminal neuralgia (TN) is a facial pain disorder characterised by recurrent paroxysms of severe unilateral pain distributed in one or more branches of the trigeminal nerve . The natConsiderable expertise is necessary for proper medical management of TN because the drugs are unspecific, mostly antiepileptics, and often have to be administered in a high dose to control the pain . FurtherRandomised controlled trials are the gold standard for assessment of efficacy and tolerability of drug treatment . Such trThis study aimed to provide evidence concerning the real-life efficacy of medical management of TN when directed by specialists. Additionally, the aim was to inspire other neurological centres to improve their TN management programs to ensure the best possible care for this patient group. We hypothesised that the two-year prognosis in a group of medically managed TN patients enrolled in a structured multidisciplinary management program was favourable, defined as a 50% reduction of the overall burden of pain over a two-year period.This study was a prospective, observational study of TN patients enrolled in a structured multidisciplinary management program at the Danish Headache Center (DHC), as previously described in detail . The proNewly referred TN patients seen between May 2012 and December 2015 were enrolled consecutively and followed-up systematically. Inclusion criteria were: recordings of the intensity of pain at enrolment of the programme (baseline recording), a two-year assessment (end-point recording), and effect and side-effects of drug treatment (at baseline and endpoint). The exclusion criteria were: initiation of medical treatment at the DHC before May 2012, neurosurgical treatment of TN within the two-year follow-up, and incomplete two-year follow-up. The number of patients enrolled in the inclusion period determined the sample size.primary TN.The diagnostic criteria used in this study were the beta version of the 3rd edition of the International Classification of Headache Disorders (ICHD-3-beta) . Until tAt enrolment, all medically managed patients were offered five fixed visits within a two-year period. Follow-up regime has previously been described in detail . In shorAt the initial visit, a routine physiological and neurological examination was performed with a special focus on the trigeminal sensory function, as previously described in detail .A 3.0 Tesla MRI scan was conducted according to a TN protocol . The TN Assessments were conducted by a neurologist or highly trained fellow in neurology at the DHC at all visits. At the initial visit, a standardised purpose-built semi-structured interview was performed by a highly-trained fellow in neurology, supervised by a senior neurologist. At the subsequent follow-up visits, the patients were assessed by the same senior neurologist. For a detailed description of the semi-structured interview see Additional file A self-complete patient survey was mailed to the patients two years after their initial visit. If the patients did not return the questionnaire, a reminder was mailed to them again 26–27 months after enrollment. If they did not return the second questionnaire, data was registered as missing. The survey included 21 qualitative and quantitative questions, corresponding the assessment schemes, concerning; overall burden of pain, pain quality, current treatment and satisfaction with treatment. Satisfaction levels were registered on a 7-point Likert Scale, anchored at 1 = very dissatisfied and 7 = very satisfied. For the analysis, the patients were considered as satisfied if 5–7 was reported on the scale, while the patients were regarded as dissatisfied if 1–3 was reported on the scale. The patients were regarded as neither satisfied or dissatisfied if they reported 4 on the scale. See Additional file Data from the control schemes and questionnaires were used to evaluate the outcome. If there was disagreement between the two-year follow-up assessment and the patient survey, data from the follow-up scheme was reported in this study.no burden of pain and 10 = worst possible burden of pain. To grade the burden of pain on the NRS, the scale was subcategorised into NRS 0 = no burden of pain, NRS 1–4 = mild burden of pain, NRS 5–7 = moderate burden of pain, NRS 8–10 = severe burden of pain [The primary outcome was a good outcome according to the overall burden of pain NRS, i.e. the number of patients who had a reduction of minimum 50% on the NRS two years after enrolment in the management program compared with baseline. NRS was anchored at 0 =  of pain . If the No pain, BNI II = Good effect: Occasional pain that does not, or only occasionally, reduce my quality of life, BNI III = Limited effect: Daily pain with a moderate reduction of my quality of life, BNI IV = Insufficient effect: Daily episodes with severe pain which significantly reduce my quality of life. If patients were not taking any TN drugs, BNI was registered as BNI = 0. Patients who were not taking any medication (BNI = 0) were subdivided into two groups a) patients in remission b) patients without medical treatment but not pain-free.The secondary outcomes were; a) poor outcome defined as no reduction of the overall burden of pain NRS over the two-year follow-up period. NRS was anchored as described above, and b) good treatment effect according to BNI defined as the number of patients who reported BNI level 0, I or II two years after enrolment. BNI I = Very good effect: Continuous and ranked data are summarized by descriptive statistics. Categorical variables are presented with frequency distributions  and with 95% confidence limits (Cl). McNemar’s, Chi-square and Fisher’s test were used to assess associations of categorical variables. Nonparametric testing (Wilcoxon signed-rank test) was used to determine the significance of differences in reported outcome measures, e.g. NRS and BNI, between baseline and endpoint assessments.p < 0.05) was found. Variables with no significant association with outcome were excluded sequentially. The predefined independent variables were sex , anxiety and/or depression (yes vs. no), disease duration (≥ 5 years vs. < 5 years), degree of neurovascular contact at MRI  and pain quality . In a previous study, which included a subset of the patients also included in the current study, we found a strong association between the male sex and a neurovascular contact with morphological changes [A multivariate logistic regression analysis with backward stepwise selection was used to test for associations between a subset of predefined variables and good outcome. The same multivariate logistic regression analysis was also conducted to test for associations between a subset of predefined variables and poor outcome. Variables were retained in the regression model if a significant association .If more than 10% of the clinical data from the semi-structured interview or two-year assessments were missing, the patient was excluded from the analyses. Missing data were considered missing at random, based on the assumption that missingness was independent of the demography, treatment, and pain level. From May 2012 to December 2015, 223 patients were enrolled in the management program. A total of 186 patients were diagnosed with primary TN and 37 patients with secondary TN  had a good outcome, i.e. a minimum reduction of 50% in the overall burden of pain on NRS, compared with baseline. Significantly more patients reported no overall burden of pain (NRS 0) (16 vs. two patients) and mild burden of pain (NRS 1–4) (63 vs. 38 patients) at their two-year assessment compared to baseline . A severe burden of pain (NRS 8–10) was reported by fewer patients (7 vs. 25 patients) at their two-year assessment compared to baseline (p < 0.001). The number of patients with a moderate burden of pain was unchanged (38 patients vs. 22 patients (p = 0.06))  to 3.00 Cl 2.47–3.53), .47–3.53,A poor outcome was reported by 33 (32%), of whom 24 patients (23%) reported no changes in the overall burden of pain, and nine patients (9%) experienced a worsening of the overall burden of pain, over time.Of the 16 patients who reported moderate or severe burden of pain at their two-year assessment, four patients underwent microvascular decompression after the two-year assessment. Seven patients were satisfied with their drug treatment, despite the increase of burden of pain during the follow-up. Two patients were referred to neurosurgical consultation but wanted time to consider the pros and cons for surgery. One patient had co-existing severe rhinitis at the time of assessment that might have worsened the TN. Thus, she was not considered a candidate for surgery, at the time. The reason for not undergoing neurosurgery was unknown in two patients.p < 0.001), reduced from a median of 2 (SD 1.31) to 1 (SD 1.16) on the BNI scale. Significantly more patients reported a good treatment effect according to BNI  at the two-year assessment (85 patients (83%)), compared with baseline (53 patients (53%)), (p < 0.001) ; suffering from other headaches (p = 0.90); hypertension, (p = 0.66); depression/anxiety (p = 0.11) or age < 40 at onset (p = 0.88). , The clinical characteristics of the medically treated patients did not differ from the characteristics of the patients who were referred to neurosurgery before their two-year follow-up Table . The neunor the two-year assessment. They continued their follow-up at the DHC due to the treatment of other coexisting headaches, primarily migraine and tension-type headache. At the initial assessment significantly more patients, 97 patients (85%), were using TN drugs, compared to 74 patients (72%) who were using TN drugs at their two-year assessment, (p < 0.001). The most frequently used drugs at the initial visit were carbamazepine (29 patients (28%)) and gabapentin (29 patients (28%))  of the enrolled patients . Seven (7%) patients did not take any medication neither at baseline p = 0.12). The median dose of oxcarbazepine at baseline was 1200 mg (range 300–2400 mg) and 900 mg (range 300–2700 mg) at the two-year assessment (p = 0.18). The median dose of gabapentin at baseline was 1600 mg (range 600–4500 mg) and 2100 mg (range 600–3600 mg) at the two-year assessment (p = 0.59) (Table The median dose of carbamazepine at the first visit was 600 mg (range 100–1600 mg) and 800 mg (range 200–1400 mg) at the two-year assessment, (p < 0.038).Combination therapy with two or more drugs was used in 22 (21%) patients at baseline. The most frequent combinations were carbamazepine and gabapentin (4 patients), or oxcarbazepine and gabapentin (4 patients). At the two-year assessment 25 patients (24%) used combination therapy. The most frequently used combinations were oxcarbazepine and gabapentin (7 patients) and carbamazepine and gabapentin (6 patients). There was a significant increase in the number of patients who were not taking any TN drugs at the two-year assessment (31 patients (29%)) compared with baseline (17 patients (17%)),  patients of whom the treatment was discontinued in 14 patients (23%), drug treatment was initiated in four patients (6%), while the type of drug was changed in 22 patients (36%). Combination therapy was altered to monotherapy in 6 patients (10%), combination therapy was initiated in 14 patients (23%), and combination therapy with three or more drugs was reduced to two drugs in 2 patients (3%).The patient survey was returned by 52 (50%) patients. Of these, 45 patients answered the questions concerning satisfaction with the treatment and level of information given at the DHC. Regarding satisfaction concerning the treatment; 9 (20%) patients were unsatisfied, 4 (9%) patients were neither satisfied nor unsatisfied, while 32 (71%) patients were satisfied. Concerning the level of information: 6 (13%) patients were unsatisfied, 13 (13%) patients were neither satisfied nor unsatisfied, while 33 (73%) patients were satisfied.n = 9, b) Did not have endpoint NRS recordings n = 6, c) Not satisfied with the treatment and did not want further follow-up, n = 4, d) Suffered from other diseases not related to TN , n = 4, e) Dead not related to TN, n = 4, f) No out-patient visits, for unknown reasons, n = 2, g) Only interested in surgical treatment and discontinued follow up at DHC, n = 2, h) Moved to another country, n = 1, i) No further treatment options according to treating physician at 1st out-patient visit, n = 1.Thirty-three patients (24%) were lost to follow-up. This was due to; a) Satisfied with current treatment and did not want further follow-up, A standardised collection of data concerning the use of non-medical treatment have not been conducted in this study. However, we estimate that 10% of the patients have used the non-pharmacological treatment offers (physiotherapists or phycologists) and estimate that over 90% of the patients have talked to the specially trained nurses. Future studies are to be conducted.This real-life prospective study demonstrates that TN patients enrolled in a structured multidisciplinary medical treatment program improve over two years with half of the patients having more than 50% reduction in the overall burden of pain. Findings are in line with a previous prospective study with a shorter follow-up (3–9.5 months), where 68% of the patients reported a 50% reduction of pain . The reavery good or good effect of the drug treatment, during the follow-up.Our results could indicate that a structured program directed by specialists is effective. It is likely that individualised drug treatment and proper dose adjustments play a role. Almost all the enrolled patients underwent individual adjustment and/or change of drug during the time of follow-up. In the group of patients who were in current drug treatment, the dosage of medication was stable as well as there were no significant changes in the use of specific types of drugs. An increased number of patients were without drug treatment as well as there was an increment in the number of patients with Although drug treatment is a cornerstone in TN management, patient-centered care including non-pharmacological therapy can improve treatment . FurtherOur results show a more favourable prognosis of TN, than the prognosis of e.g. painful diabetic neuropathy. A recent study of treatment of painful diabetic neuropathy reported that only 30% of the patients, treated at a tertiary centre, reported a good outcome, defined as a 30% reduction of pain and 1-point reduction on the Pain Interference Scale . WhetherIn a recent study, we found that the male sex and a neurovascular contact with morphological changes of the trigeminal nerve are strongly associated with a good outcome of microvascular decompression . Based oOur results do show that patients with coexisting chronic pain had poorer odds of a good outcome than patients without coexisting chronic pain. This is in line with previous studies demonstrating that complex patients with multiple pain conditions are more difficult to treat . AnotherOur results show that TN does not generally seem to progress. In our cohort, which might be expected to be the most difficult to treat, only a small subset of patients (apart from those referred to surgery) reported worsening of pain.The current findings contradict the proposed natural history theory of TN as a progressive disorder that, over time will result in increased frequency and intensity of pain concomitant persistent pain and sensory disturbances , 29. TheOur results could reflect that the natural history of TN is rather that of a non-progressive or slowly wearing off nature, or the results could reflect a regression towards the mean. To be able to make any final conclusions on the natural history of the disease, RCTs and even longer-term studies are needed. However, whatever the explanation for the current results, the findings do indicate that TN patients improve over a two-year period given that they are managed in a multidisciplinary setting directed by specialists, i.e. physicians, nurses, psychologists and physiotherapists.Our results are representative only for those TN patients who were medically managed and not referred for surgery. Fifty of those patients who were initially enrolled in the management program were referred to Department of Neurosurgery due to unsatisfactory management of their TN pain. We recently reported a favourable outcome for the selected group of TN patients who underwent a microvascular decompression at the Department of Neurosurgery . The proCurrent TN guidelines recommend that if carbamazepine or oxcarbazepine treatment fails, patients are considered medically refractory and neurosurgical treatment is the next step . The resThe patients with a poor outcome of the medical management in our cohort were all offered neurosurgical treatment, but many opted out of surgery. We hypothesise that it is either due to a relatively low overall burden of pain or fear of surgery, that holds the patients back for surgery. In Denmark healthcare is free why financial problems is not a barrier to surgery.The prospective design with standardised and systematic assessments of the patients and the set up as a real-life study in a clinical setting are the major strengths of this study. Real world data is difficult to acquire but does offer a more realistic view of the situation in the clinic due to fewer exclusion criteria. Although treatment practice was in line with international guidelines , choice The burden of overall pain was restricted to evaluate the patients’ evaluation of the average pain frequency and intensity, as opposed to a broader definition used by Tölle et al. . It reprThis study is hypothesis-generating regarding the explanation of the favourable prognosis of TN. To be able to explain the causes of favourable prognosis, case-control studies or randomised controlled trials are required. Although randomising TN patients into subgroups where some patients are not given any preventative drugs or the neurosurgical procedure is postponed, would raise major ethical concerns. Future studies using a similar methodology from other specialist centres, as well as studies of even longer follow-up, are warranted to produce more real-life data and shed light on prognosis, treatment and the natural history of TN.This large prospective real-life study demonstrates that patients enrolled in a structured multidisciplinary TN management program at a specialist centre improve considerably over time. Thus, TN does not seem to be a disease with invariable progression in contrary to what has previously been assumed. The reasons for improvement could be several; optimisation of drug treatment, continuous advice and education and support by the multidisciplinary team, referral of the medically intractable patients for surgery or the natural history of the disease. The favourable prognosis provides hope and optimism for patients and care providers and suggests that specialist management of TN is highly rewarding.• In TN patients who are managed in a multidisciplinary centre, the level of pain decreases over time and medication dosages remain stable• Prognosis in medically treated TN patients is not dependent on concomitant persistent pain, neuroimaging findings or sex• Findings indicate that TN is not an invariably progressive disease and provides optimism and hope to clinicians and patients that medical treatment of TN by experts is highly rewardingAdditional file 1:Supplementary material S1. Trigeminal neuralgia semi-structured interview. (DOCX 35 kb)Additional file 2:Supplementary material S2 - Trigeminal neuralgia patient survey. (DOCX 27 kb)Additional file 3:Supplementary material S3. Association between changes in the overall burden of pain and clinical characteristics. (DOCX 31 kb)


The aim of the study was to analyze the effect of the treatment given to patients in a pain clinic on their assessment of pain intensity and the incidence of emotional disturbances in the form of anxiety, depression, and aggression. The study was conducted from January 2014 to April 2018 among patients under the care of two Warsaw pain clinics. The study tools were the Hospital Anxiety and Depression Scale—Modified Version (HADS-M) and the Numerical Rating Scale (NRS). The project enrolled 325 patients, with women comprising 60.62% of patients, and the age bracked of 65–79 years comprising 39.38% of patient. The major reasons for attending the pain clinic were osteoarticular pain (44.92%) and neuropathic pain (42.77%). The therapy applied lowered the patients’ pain intensity (4.98 vs. 3.83), anxiety (8.71 vs. 8.12), aggression (3.30 vs. 3.08), and the overall HADS-M score (18.93 vs. 17.90), which shows that the treatment of both the pain symptoms and the associated emotional disturbances in the form of anxiety and aggression was effective. Sex is a factor affecting pain intensity. The level of mental disorders was influenced by the sex and age of the patients and how long they had been treated in the pain clinics. International Association for the Study of Pain (IASP), which promotes research in the scientific, practical, and educational aspects of this field [“an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” [According to the is field ,2, pain  damage” ,4,5. The damage” .International Association for the Study of Pain (IASP) recommends interdisciplinary treatment of patients with chronic pain, underlining the need to address not only the aspect of the patients’ somatic feelings but also biological, psychological, and social factors in the model of pain management and to implement psychological, social, recreational, and professional training. Pharmacotherapy remains the basic method of treatment, but it should comprise an element of a complex program of rehabilitation, whose final effect is not only to lower pain intensity but also improve the patients’ quality of life and make it possible for them to return to their families and to society [Chronic pain is a little-known condition which poses a major challenge to modern medicine, since it is difficult to diagnose and to find appropriate management for each case. In spite of the continuous development of medicine resulting in greater accessibility of new treatment methods and the development of new-generation analgesics, many attempts to eliminate pain from everyday life end in failure. The  society ,8,9,10.Since the process of diagnosing and treating pain is complex, it requires comprehensive planning, which demands specialist knowledge and experience from doctors dealing with the problem of pain management. Interdisciplinary treatment of patients suffering from pain is possible in specialized organizational units that are being set up in many countries. An example of such units are clinics and counseling centers for pain management. Their primary objectives are to treat patients with acute and chronic pain, educate both healthcare personnel and patients, and participate in the preparation of guidelines and research in the field of pain ,11,12.The problem of pain management has now become such an important issue that the authors decided to undertake research aiming to analyze the effect of the treatment offered in pain clinics on the intensity of pain and the incidence of emotional disorders in the form of anxiety, depression, and aggression.Research was conducted in patients under the care of two outpatient pain clinics in the city of Warsaw: The Pain, Anesthesiology and Intensive Therapy Clinic of the Medical University of Warsaw, 4 Lindleya Street, as well as the Pain Clinic located at 231 Czerniakowska Street (Poland). It took place from January 2014 to April 2018. The inclusion criteria for participation in the study were as follows: 18 years of age, ascertainment of pain on the basis of the patient’s medical history, and attending a pain clinic in the city of Warsaw. The exclusion criterion was the lack of informed consent on the part of the patient. The study obtained approval no. AKBE/24/15 from the Bioethics Committee of the Medical University of Warsaw. It was, moreover, approved by the managers of the clinics involved. The patients taking part in the project were informed about the voluntary nature of their participation, their anonymity, and the fact that the results of the study would be used exclusively for scientific purposes. The study assessed the level of pain intensity and emotional disturbances in the form of anxiety, depression, and aggression in the patients who agreed to participate in it during their first and subsequent visit in the above-mentioned pain clinics.Research was based on the analysis of the medical histories of the patients attending the pain clinic (their sociodemographic data) as well as by the diagnostic survey method using the questionnaire technique. The research tools were: The Hospital Anxiety and Depression Scale—Modified Version (HADS-M) and the Numerical Rating Scale (NRS).The Hospital Anxiety and Depression Scale—Modified Version (HADS-M) is a revision of the Hospital Anxiety and Depression Scale (HADS) developed by Zigmond and Snaith , and wasThe Numerical Rating Scale (NRS) is a one-dimensional measurement of pain intensity in adults. The most frequently used version is the 11-point NRS scale, which was the one used in the present study. The NRS form can be filled out by the patients either by reporting the scores verbally or by writing them down on their own. The respondents are asked to rate their pain giving a numerical score to its intensity. The NRS score ranges from 0 to 10, with 0 indicating no pain and 10 the worst possible pain. Higher scores on the NRS scale indicate a higher intensity of pain ,17.M) and standard deviation (SD) are shown.The data collected from the survey questionnaires were analyzed using the STATISTICA version 13 software . Amounts and percentages were used in the description of quality data, while in numerical data—the mean  were compared using the Wilcoxon matched-pairs signed-ranks test. The differences between the two groups were analyzed by means of the Mann-Whitney U-nonparametric test, while the Kruskall-Wallis test was performed to compare more than two groups of variables. The study assumed statistical significance as SD 14.73). The main reasons for attending the pain clinic were osteoarticular pain (44.92%) and neuropathic pain (42.77%). Over half of the group studied were given specialist multimodal therapy treatment (59.69%), with antidepressant drugs being the most frequent medication (56.31%). The patients had usually been attending a pain clinic for over two years (29.54%) (The study enrolled 325 patients treated in pain clinics. Women dominated in this group (they comprised 60.62% of those enrolled), while most of the overall group of patients were in the 65–70 age bracket (39.38%), with the mean age being 62.17 years ((29.54%) .The statistical analysis that was conducted—which took into account both the changes in pain intensity measured on the NRS scale and emotional disturbances in the form of anxiety, depression, and aggression evaluated on the HADS-M scale between the first and the subsequent visit in the pain clinic—showed a statistically significant difference in the case of pain intensity, the level of anxiety and aggression, and the overall result on the scale. As a result of the therapy undertaken in the pain clinics, the patients obtained lower values expressing pain intensity, anxiety, depression, and the overall HADS-M score. In the case of depression, the difference was not statistically significant .p < 0.05). It follows from the study that women and younger people had a higher level of anxiety during the first visit, patients who had been treated for 4 to 12 months showed the highest level of depression, and the group of patients under 34 years of age who had been treated at the pain clinic for between four and twelve months showed a significantly higher level of aggression. When examined on the subsequent visit, the analysis indicated significant differences between pain intensity versus the level of anxiety, the duration of treatment versus the level of depression, and the age of the patients versus the level of aggression (p < 0.05). During the subsequent visit at the pain clinic, women reported a significantly higher pain intensity and anxiety level than men, and patients aged 35–49 demonstrated the highest level of aggression. A significantly higher level of depression was found in patients who had been treated for two years or longer. Analysis showed statistically significant differences during the first visit in pain clinics between the sex and age of patients compared to the level of anxiety, and, similarly, between the duration of treatment versus the level of depression as well as between the duration of treatment compared to the level of aggression  devoted to adult patients treated in the University Hospital Limerick in Ireland . Moreove18 devoteIn the present study, the authors made two measurements to assess the pain intensity and the level of emotional disturbances. The first one was performed in the pain clinic when the patients first came there and the next one was performed during their subsequent visit. It follows from the analysis conducted that the level of pain intensity, anxiety, aggression, and the overall result on the HADS-M scale underwent significant changes as a result of treatment in the pain clinics: the respective scores fell and were 4.98 vs. 3.83 for pain intensity, 8.71 vs. 8.12 for anxiety, 3.30 vs. 3.08 for aggression, and 18.93 vs. 17.90 for the overall HADS-M. Thus, both the treatment of pain intensity given at the pain clinic and the associated emotional disturbances in the form of anxiety and aggression proved to have been effective. Pain is closely linked to the occurrence of emotional disturbances, which is confirmed by the studies of Pakpou et al. (2018), Sagheer et al. (2013), and Ahmed et al. (2013) ,25,26. TThe further part of our study was devoted to assessing the impact of sex, age, and duration of treatment on the level of pain intensity and disorders taking the form of anxiety, depression, and aggression. The results of our own studies indicated that during the first visit women scored higher on the scale of anxiety, while during the subsequent visit they scored higher on both anxiety and pain intensity in comparison to the studied group of men. Patients in the 35–39-year age bracket demonstrated the highest level of anxiety, while those under the age of 34 years had the highest level of aggression both during the first and the subsequent visit. Patients whose duration of treatment was from 4 to 12 months indicated the highest levels of depression and aggression during their first visit, while during the subsequent visit those who had been treated for over two years demonstrated the highest level of depression on the HADS-M scale. In the study done by Vanhaudenhuyse et al. (2014), the authors also pointed out the influence of sex on patients with chronic pain. They observed that women indicated a higher level of anxiety and depression measured on the HADS scale. Similar results were reported in the study by Nolen-Hoeksema (2001) ,35. It eThe authors of the present paper undertook this study in order to report the influence of the treatment of patients in pain clinics because they found no such reports in Polish literature. The study has some limitations. It was done in only two pain clinics in Poland and reports only a few types of pain. Moreover, the authors analyze selected determinants. However, due to the importance of pain management and associated mental disorders in the world today, it is reasonable to continue research on this subject. A better understanding of this field of knowledge will improve the social awareness of the existence of pain clinics and help ensure the best possible diagnostics and management as well as the high quality of specialist care in pain clinics.The most frequent reason for patients undertaking treatment in pain clinics was osteoarticular and neuropathic pain. Women and people in the 65–79 age bracket were the most frequent patients in this group. Treatment in pain clinics has a positive impact on pain intensity and the level of anxiety and aggression in patients with pain symptoms. Sex is a factor that influences the level of pain intensity. The level of mental disorders is influenced by the patients’ sex and age.


To determine the caecal intubation time depending on bowel preparation as per Boston Bowel Preparation Scale.This cross-sectional study was conducted at Dr. Ruth K. M. Pfau, Civil Hospital Karachi between August 2018 to February 2019. A total of 201 patients were included in the study. Time was recorded from insertion of colonoscope to the time required to reach the cecum. Bowel preparation was graded during withdrawal of colonoscope by using Boston Bowel Preparation Scale. Pearson Correlation test was used to study correlation of BBPS scores with CIT, gender, BMI, adenoma and polyp detection.In this study 201 patients undergoing colonoscopy were included. Mean ±SD of age of patients was 36.9 ±15.8 years. Out of the 201 patients 112 (56%) were males and 89 (44%) were females. The results of our study showed that increased Boston Bowel Preparation Scale Scores were associated with decreased caecal intubation time. The mean CIT was 10.7 ±5.4 minutes and Pearson correlation was significant at 0.002. Significant correlations of BBPS were also found with BMI and adenoma detection.The diagnostic effectiveness of colonoscopy depends upon the quality of the preparation. Good bowel preparation improves the speed of colonoscopy and its completeness. Caecal intubation time is defined as the time required to reach caecum after insertion of colonoscope. It indicates the difficulty of advancing the scope till caecum.6Another scale named as Boston Bowel Preparation Scale (BBPS) is considered as a novel scale for rating of bowel cleanliness has received good intra and inter-observer reliability assessments and is designed for researches related to colonoscopy and bowel preparation.9Our objective was to determine the impact of bowel preparation on caecal intubation time, as good bowel preparation will lead to shorter caecal intubation time, better visualization of mucosa and polyp detection.This cross-sectional study was conducted at Dr. Ruth K. M. Pfau, Civil Hospital Karachi between August 2018 to February 2019. Non-probability consecutive sampling was used for selection of patients. Approval was taken from the Institutional Review Board of Dow University of Health Sciences.All patients between the ages of 18-70 years undergoing colonoscopy were included. Exclusion criteria: Patients who were unable to tolerate colonoscopy preparation solutions and patients having electrolyte abnormalities to whom colonoscopy preparation solution could not be given, were excluded.A written informed consent was taken from the patients undergoing colonoscopy. Patients were advised to take colonoscopy preparation solution at 12 PM then at 6 PM the day before colonoscopy. They were advised to take liquid diet for 24 hours before colonoscopy and nil oral orders for four hours before colonoscopy. Each colonoscopy preparation kit contains two 45 ml bottles of solution. Each 45 ml bottle contains: sodium sulfate 17.5 grams, potassium sulfate 3.13 grams, magnesium sulfate 1.6 grams. Inactive ingredients include sodium benzoate NF, sucralose, malic acid FCC, citric acid USP, flavoring ingredients, purified water, USP. The solution is diluted to a final volume of 500 ml with water before intake. Colonoscopy were done by three skilled colonoscopists which in study were called as A, B & C. Time was recorded from insertion of colonoscope in anus till caecum is reached. Bowel preparation was graded during withdrawal of colonoscope by using BBPS from 0 to 3, where higher score means good bowel preparation, details of Boston Bowel Scale is given as under:0 = poor preparation with solid stool on mucosa that cannot be cleaned and hinder the mucosal visualization.1 = some mucosa seen while rest of mucosa cannot be seen due to solid or loose stool.2 = some mucosa cannot be seen due to solid or loose stool while rest of mucosa is visualized.3 = good preparation and visualization of entire mucosa.7It is the sum of three individual segments scale.First Segment Caecum & Ascending ColonSecond Segment Transverse Colon with Hepatic & Splenic FlexuresThird Segment Descending, Sigmoid Colon & RectumThe impact of bowel preparation on caecal intubation time was analyzed separately for individual colonoscopists as well as combined for all three too. BBPS scores was correlated with CIT, gender, BMI, adenoma and polyp detection using ‘Pearson Correlation Test’. Value of ≤0.05 was taken as significant.In this study 201 patients undergoing colonoscopy were included. Three colonoscopists from our department participated in this study. Out of the 201 colonoscopies, 72 were performed by Colonoscopist-A, 35 by Colonoscopist-B and 94 by Colonoscopist-C. Mean ±SD of age of patients was 36.9 ±15.8 years. Out of the 201 patients 112 (56%) were males and 89 (44%) were females. Mean age of males was 34.8 ±16.6 years while that of females was 39.6 ±14.5 years. The difference in age among gender was statistically significant . Mean BMI of patients undergoing colonoscopy was 24.2 ±3.5. Mean BMI of female was significantly more as compared to males . Mean caecal intubation time was 10.7 ±5.4 minutes. In males it was 10.4 ±5.2 minutes while in females it was 11.2 ±5.6 minutes. Difference between caecal intubation time in males and females was not significant . Details are given in A total of four adenomas were detected by Colonoscopist-A whereas no adenomas were detected by Colonoscopist-B and C. A total of 29 polyps were detected out of which 14 (48.3%) polyps were detected by Colonoscopist-A, 3 (10.3%) by Colonoscopist-B and 12 (41.4%) by Colonoscopist-C.The caecal intubation rate was 100% by all three colonoscopists. The mean CIT of Colonoscopist-A was 9.2±4.2 minutes, Colonoscopist-B was 14.9±6.6 minutes and of Colonoscopist-C was 10.4±5.0 minutes. Difference in caecal intubation time was significantly different among the three colonoscopists when tested with ANNOVA (P <0.001). The correlation of CIT with BBPS by all three colonoscopists combined showed strong correlation with two tailed correlation at 0.002. Individual colonoscopists caecal intubation times also showed strong correlation with BBPS scores, details are given in The BBPS has been validated in a number of clinical trials.12In our study we aimed to determine CIT &, rate and correlate the CIT with BBPS score. Secondary objective was to see adenoma detection rate and correlation of BBPS score with BMI. The results of our study showed that increased BBPS score, i.e., good colon preparation was associated with short CIT. The result of our study corresponded with the earlier studies where mean caecal intubation time was found to be shorter with increased BBPS score.et al. in their study reported 5251/9223, i.e., 56.9% objectively confirmed complete colonoscopies and in 1913/9223 (20.7%) procedures the endoscopist was unable to complete the colonoscopy.15Caecal intubation was considered successful if caecal landmarks  were photo-documented. Bowles C As the colonoscopies were performed by three colonoscopist so difference in their duration of experience and technique may contribute to CIT. But we try to minimize this confounder by assessing mean CIT with BBPS by all three colonoscopist separately also. Another limitation of this study was that patient’s pain tolerance was not assessed prior to colonoscopy which may also contribute to the speed of colonoscopy. We used sedation and analgesia prior to every individual colonoscopy to minimize this difference in pain threshold. Another limitation of this study was that it was done in single center.The diagnostic effectiveness of colonoscopy depends upon the quality of the preparation. This study showed that good bowel preparation improves the speed of colonoscopy, its completeness, rate of polyp and adenoma detection.HA: Did coloscopies, Study Conception.TR: Data collection, initial manuscript writing.MAS: Did colonoscopies, manuscript review and statistical analysis.FSA: Manuscript writing and statistical analysis.BFZ: Did colonoscopies, final corrections and approval of manuscript, is responsible for integrity of research.AAS: Data collection, initial manuscript writing.


Post-operative pain after open cholecystectomy can result in increased oxygen consumption, atelectasis, pneumonia, decreased vital capacity, and increased morbidity and mortality. The aim of this study was to compare the analgesic effects of intrapleural meperidine and intravenous morphine in controlling post-cholecystectomy pain.In a double-blinded randomized clinical trial, 72 patients who were candidate for elective open cholecystectomy, were divided randomly into two groups based on accidental randomized numbers. Anesthesia technique was precisely the same for all patients. At the end of surgery, 50 mg of meperidine  was injected intrapleurally for meperidine group patients; whereas, 0.1 mg/kg intravenous morphine was injected intravenously in control group. Onset of pain and total dose of rescue analgesic were measured.In order to obtain a Numerical Rating Scale (NRS) <3, the difference in morphine consumption up to 12 hours in two groups (4.4 ±1.7 mg in meperidine group & 5±2 mg in control group) was not statistically different. However, the first request for analgesia in meperidine group was delayed significantly longer than the control group (146.6 ±6.8 minutes in meperidine group & 40 ±1.8 minutes in control group).A single injection of intrapleural meperidine can delay the first request for analgesia in open cholecystectomy compared to intravenous morphine. Cholecystectomy is one of the most common surgeries worldwide. Early post-operative pain is the most common complaint of patients on the first day after laparoscopic or open cholecystectomy. Post-cholecystectomy pain could decrease Functional Residual Capacity (FRC), decrease vital capacity, and induce desaturation particularly in recovery time. Post-operative pain increases morbidity of patients .Systemic opioids are mainstay of post-cholecystectomy analgesia in many settings, but respiratory depression, nausea, vomiting and ileus are common side effects of opioids. The high incidence of post-operative pain and risk of respiratory incompetency due to decreased FRC and vital capacity indicates the need to control this pain.Intrapleural analgesia has been proposed as an effective method for controlling the postoperative pain, preservation of lung function after thoracotomy or cholecystectomy, and reduction of post-operative pulmonary complications . The mecMeperidine is an opioid with local anesthetic effect. Intrapleural meperidine could be a safe option with higher efficacy for post-cholecystectomy pain.Our aim was to compare the analgesic effects of intrapleural Meperidine and intravenous morphine in controlling post-cholecystectomy pain.The study was reviewed and approved by the Shahid Beheshti University of Medical Sciences Ethics Committee and performed in accordance. Information about the study was given comprehensively both orally and in written form to all patients or their accompanying adult. They gave their informed written consents prior to their inclusion in the study.In a randomized double blind study, 80 patients candidate for elective cholecystectomy were enrolled in this study, 8 patients were excluded due to change in the surgical technique, prolonged operation or transferring the patient to the intensive care unit (ICU) at the end of procedure. Finally, the data of 72 patients were collected. The trial was registered in the Iranian Registry of Clinical Trials under the registration number of IRCT20151012024493N3.Inclusion criteria were patients with ASA class I and II, no addiction to drugs, no long-term analgesic use, no history of thoracotomy, age between 18 and 60 years, and Body Mass Index (BMI) between 18–30. Exclusion criteria were development of respiratory distress in recovery, duration of surgery >150 minutes, change of surgical incision other than Kocher right subcostal, and major complication of cholecystectomy procedure.2 for 3 to 5 min. For premedication, fentanyl 3 μg/kg and midazolam 0.03 mg/kg was administered. The anesthesia induced with propofol 2 mg/kg/IV and lidocaine 1.5 mg/kg/IV and cisatracurium 0.2 mg/kg/IV. Intubation was performed under smooth direct laryngoscopy after 5 minutes when TOF=0. Endotracheal tube size was selected after laryngoscopy under direct visualization. Anesthesia was maintained with propofol 100–200 μg/kg/min/IV, remifentanil 0.05 μg/kg/min/IV infusion and cisatracurium 0.05 mg/kg every 30 minutes and 50% Nitrous oxide/50% Oxygen to keep the depth of anesthesia between 40 and 60 on Cerebral State Monitoring (CSM).Method of anesthesia was the same in both groups. Patients were pre-oxygenated with 7 L/min 100% OAt the end of surgery, in meperidine group, 50 mg of meperidine was diluted in 20 ml normal saline and injected into intrapleural space. In control group, intravenous morphine was injected at 0.1 mg/kg/IV. To blind the study, meperidine group received 0.1 ml/kg/IV normal saline  and control group received 20 ml of intrapleural normal saline. Data collection was performed by a different physician who performed the injections.Intrapleural injection was performed at the end of surgery when surgical incision was closed. Patient was reversed by neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg), while propofol and remifentanil infusion continued. Patient breathed spontaneously, then a Tuohy needle was applied. The technique for intrapleural block was performed with the patient in a supine position. The 5th intercostal space was identified. The needle was inserted about the midaxillary line, and an epidural needle tip was advanced until it touched the rib and then the needle walked up to rest on the cephalad edge of the rib and advanced slowly over the superior edge of the rib. When the tip of the needle entered the parietal pleura, the hanging drop was drawn into the chest cavity because of the negative intrathoracic pressure and then the prepared solution injected. Control CXR was performed to rule out pneumothorax. Then physical examination was performed to detect the subcutaneous emphysema.Pain score was recorded by using Numerical Rating Scale (NRS) The first time to request rescue morphine analgesia, total dose of administered morphine during 12 and 24 hours after surgery and NRS was recorded in prepared data sheets.A total number of 80 patients were enrolled in the study and 4 patients were excluded from each group. Age, sex, body weight and duration of surgery were not significantly different between two groups of study (P>0.05) .Visual Analogue Scale-VAS>3) was significantly longer in meperidine group (146.6±18.5 minute) compared to control group (40.5±15.1minute) (P=0.001) (Onset time of pain (P=0.001) .Although the total dose of morphine in the next 12 and 24 hours post-operative was lower in meperidine group compared to control group , it was None of patients developed pneumothorax in control CXR performed after surgery.In this study we assessed intrapleural meperidine versus intravenous morphine in control of the post-cholecystectomy pain. Our results showed that intrapleural meperidine is effective in deterring post-cholecystectomy pain in comparison to placebo.Onset of pain was significantly longer in meperidine group compared to intravenous morphine. Morphine is a more potent opioid in comparison with Meperidine and has higher affinity to central μ receptors. This effect implies the fact that local anesthetic effect of meperidine in controlling post-cholecystectomy pain is superior to central effect of opioids.Total dose of rescue morphine was not significantly different between the two groups of study. This also emphasizes that intrapleural meperidine is effective through its peripheral local anesthetic effect. Meperidine local anesthetic effect is transient and last for 3 to 4 hours, and thereafter systemic analgesic is required.Several mechanisms have been proposed for local anesthetic-like effect of meperidine. Although less potent in comparison with lidocaine, meperidine blocks voltage-dependent Na+ channels with molecular pharmacologic features of a local anesthetic . MeperidIntrapleural analgesia has been described as a successful method for post-operative pain following open cholecystectomy and in patients who sustained several unilateral rib fractures . In partIntrapleural injection of local anesthetics has been debated and results from various studies that are controversial. In Strömskag et al. study, median time interval from the intrapleural injection to administration of supplementary analgesics was 260 minutes for 20 ml 0.25% bupivacaine .In another study, intrapleural bupivacaine decreased post-operative pain in open cholecystectomy surgeries . On the Although our results showed that intrapleural meperidine is an effective procedure to decrease post-cholecystectomy pain; however, further researches with higher sample size are needed to demonstrate the actual efficacy of different methods of analgesia. The main side effect of this method is minimal risk of pneumothorax  which weIn conclusion, intrapleural meperidine is an effective treatment for post-cholecystectomy pain which significantly delays onset of pain in these patients. This method could be a suitable alternative in post-cholecystectomy pain control.