Introduction: This study looks at the outcome of 352 patients that underwent the “Manchester groin repair” in the period from 2007 to 2016. The effect of laterality on chronic groin pain and the reduction of pain scores post-surgery are evaluated as well as the rate of hernia recurrence for the inguinal hernia repairs.Methods: The “Manchester groin repair” is a modification of a laparoscopic totally extra-peritoneal approach with fibrin sealant mesh fixation. Data were collected prospectively. In addition to demographic data and the European Hernia Society classification grading of each hernia, pain scores were assessed prior to surgery and at 4–6 weeks post-operatively using a ten-point visual analog pain scale. Data were collected on a bespoke database and differences between time-points analyzed by non-parametric Wilcoxon signed rank tests with Kruskal-Wallis rank sum test for three-group comparisons. Significance was at the P < 0.05 level. The study was undertaken as an institutional audit.Results: Three hundred and fifty two patients underwent TEP repair as per the “Manchester Groin Repair” modification during the period of interest with a median follow-up period of 109.5 (IQR 57.0–318.5) weeks. Of these 274 (77.8%) were for the repair of true hernias and 78 (22.2%) were for inguinal disruptions.P < 0.001). Pre-operative pain scores were higher for those with a bilateral hernia , but there was no difference in post-operative scores (P = 0.347). One patient (0.3%) presented with chronic groin pain (pain after 3 months).All inguinal hernia repairs patients were evaluated ; median [interquartile range] age 50 (39–65) years. There were 75 right inguinal hernias (27.4%), 39 Left inguinal hernias (14.2%), and 160 bilateral inguinal hernias (58.4%), giving a total of 434 hernia repairs. During follow-up there were 6 recurrences (1.4%).Of the 274 patients evaluated, 145 (52.9%) had both pre and post-operative pain scores available. Median pre-operative pain score was 5 [IQR 4–7]. Median post-operative pain score was 1 [IQR 1–2]. This difference was significant (Conclusion: This study demonstrates that the “Manchester groin repair” provides an excellent repair with a low rate of recurrence and low incidence of chronic pain. Longer-term evaluation and larger patient series will add to the understanding of the role of this procedure in groin hernia repair. The success of Inguinal Hernia repair is measured by the combination of a low recurrence rate together with a low incidence of post-repair chronic pain. Recently, with heightened media interest , there hA consensus statement on CPIP in 2007 established its definition and alluded to numerous possible aetiologies of the pain that include the mesh itself and other materials used in traumatic mesh-fixation . AvoidanLaparoscopic or minimal access repair, in addition to a reduction in CPIP, have been shown to have an earlier return to normal activity and less immediate postoperative pain  10&12).&12.10&12The totally extra-peritoneal (TEP) repair is one minimal access technique that has been shown to provide a reduction in pain (CPIP) when performed with no method of mesh fixation –15 and wThe Manchester groin repair has therefore been fashioned over the last 10 years in response to the rapidly changing landscape of inguinal hernia surgery, from open to minimal access, and as a product of the first-hand experience of a high-volume operator. To the author's knowledge, this is the first report of this TEP repair modification. It includes detailed explanation of the rationale for the technical elements described such as the novel approach to the localization of mesh-fixation using FS.This study relies on the use of contemporaneous data collected on a secure NHS trust database on patients who presented with uncomplicated primary and recurrent inguinal hernia or inguinal disruption. Careful follow up, including serial visual analog pain scores and assessment for recurrence, were documented. A qualified statistician undertook all subsequent analyses.A retrospective audit of patient and outcome data for patients undergoing inguinal hernia repair by the “Manchester Groin Repair” (see Table Patients are included that underwent the “Manchester Groin Repair” from March 2007 to March 2017 (10 years).All patients aged 18 years and above were included in the study. Data was collected that includes: patient demographics, hernia type and size  and 1, [0–2], respectively] post. Testing the change scores to see whether they come from a similar distribution, the p-value 0.040 suggests we should reject the null hypothesis that the changes in the three groups are from similar distributions. The post-hoc test suggests that the change in pain scores is significantly different for those with bilateral vs. right hernias (p = 0.035).Those with a bilateral hernia appear to have a larger degree of pain pre surgery, followed by the left side (median [IQR] 6 [4.0–8.0] vs. 5 [4.5–6.0] vs. 4 [2.0–6.0]), all of which fall to a median level of 1 , [0–2], and , respectively] post-surgery. Testing the change scores using a Kruskal Wallis test to see whether they come from a similar distribution, the p-value of 0.329 suggesting no difference between the change in pain in the operation groups  but only 1 of them required an intervention with needle aspiration. Other complications included hydrocele of the cord, haematoma formation and testicular discomfort. There were no re-operations within 3 months and no early recurrences as well as any reported deaths or re-hospitalization.Hernia surgery remains a technique driven surgical entity. What constitutes a good repair remains a contentious question and in consequence any particular repair can be recommended by a surgeon with a high volume practice depicting evidence of good outcomes , 20. RecEarlier publications evaluated surgical management options for patients suffering with chronic pain following IHR where various methods of treatment were examined; mesh removal, selective neurectomy, removal of surgical clips as well as the use of diagnostic, and therapeutic analgesics and anesthetic agents. The overall level of evidence included in this review was not of a robust enough standing by being based on largely subjective data and evidence. Therefore, despite the reports of favorable outcomes in individual cases, no clear conclusions can be drawn on what exactly causes CPIP, it is likely that a multitude of factors are responsible . DespiteThe use of FS, a composite of fibrinogen and thrombin preparations, is now a well-established and recognized method for mesh-fixation. For TEP repair, mechanical integrity was first shown in animal experiments  and alsoThe “Manchester Groin Repair” relies on the use of FS to achieve fixation in key areas, namely the inferiolateral and inferiomedial edges as well as at least 3 cm below the ilio-pectineal ligament on the obturator fascia, using a slightly larger (15 × 12 cm) mesh size than that which is commonly used (15 × 10 cm) for laparoscopic repair.In the author's experience, currently very few open and laparoscopic surgeons opt for a no-fixation method of mesh placement in day-to-day practice. This move toward no-fixation may be too much of a “jump”. Given the aforementioned recommendation that there is still a need to fixate mesh prostheses in some instances, namely a large direct hernia (M3 and above) , it is lRecent international guidelines have reviewed 23 RCTs relating to mesh material and clinical outcomes and subsequently state that the evidence supports the contention that mesh characteristics influence clinical outcomes . Key chaAny mesh prosthesis used is required to obtain adequate coverage of the hernia defect and so reduce the risk of recurrence. Study of the TEP repair with a 15 × 7.6 cm mesh prosthesis resulted in unacceptably high levels of hernia recurrence and it was therefore recommended that a 15 × 10 cm mesh prosthesis be used as a minimum , 36. In This study, albeit with not large numbers, provides more evidence for atraumatic mesh-fixation with FS. In addition, it outlines the role of selective application of FS at key areas within the groin. It includes the recommendation of a relative increase in dissection to be undertaken; at least 3 cm below the ilio-pectineal “Cooper's” ligament. This creates a space for mesh-fixation to the obturator fascia. The results demonstrate that this technique has the potential to be highly efficacious. A reported low rate of recurrence (1.4%) and very low incidence of CPIP (0.3%) especially with a median follow up of 110 weeks, the author feels that these technical adaptations are in keeping with the steps that hernia surgeons will be willing to undertake in a transition toward atraumatic mesh-fixation and no-fixation during inguinal hernia repair.This case series provides evidence and rationale of a safe and efficacious modification of the established TEP repair. This information supports that a surgeon establishing laparoscopic hernia practice will consider the use of a lightweight, wide-pore mesh of a good size (15 by 12 cm) and achieve mesh-fixation with an atraumatic method e.g., Fibrin Sealant (FS). This combination assures a relative low incidence of post-herniorrhaphy pain, both acute and chronic, and a low incidence of hernia recurrence.Data from a high volume hernia surgeon; is the high volume nature of practice the real benefactor to the favorable results seen here or is it the technical alterations (most likely a combination of the two).The numbers are small but the follow up spans over a long period, but although not all patients were able to provide VAS pain scores.Ethics approval was sought and advised that this retrospective data analysis is exempt from Ethics and this has been defined in the methodology. The study was registered as an audit with Manchester University Foundation NHS Trust.JP: Writing of manuscript and data analysis. MO, MZ, PS, AKS, and SJ: Data analysis, editing of manuscript. AJS: Operating surgeon, data analysis, writing and editing of manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of this retrospective study was to assess the frequency of orofacial  and temporomandibular joint (TMJ) and/or masticatory muscle pain in orthognathic patients in a tertiary institution. A total of 286 consecutive patients undergoing sagittal split osteotomy from 2014 to 2016 were included. Thirty-nine (13.6%) patients presented with TMJ pain and 10 (3.5%) with orofacial nonodontogenic pain before orthognathic surgery; 79.6% (39/49) of these patients had no pain 1 year after surgery. Twenty-nine patients (12.2%) with no preoperative orofacial pain and 22 (9.3%) without preoperative TMJ pain presented with pain 1 year after surgery. Fifty-one (17.8%) of the 286 patients treated for orthognathic cases at our center over the 3-year period presented with pain 1 year after surgery. Most patients were managed conservatively with nonsurgical therapeutic modalities including counseling, physical therapy, warmth application, and bilateral chewing and splint therapy. In patients with TMJ pain refractory to conservative treatment, arthroscopic surgery was advised and successful in all patients for both pain reduction and improvement of the maximal interincisal opening. TMJ symptoms do develop after orthognathic surgery in patients with and without a previous history of TMJ complaints. Most patients can be managed with nonsurgical therapeutic modalities. Orthognathic surgery corrects dentofacial deformity and a wide range of minor and major skeletal and dental irregularities. Severe malocclusions are associated with aesthetic impairment, functional problems, and temporomandibular joint (TMJ) and orofacial pain , 2. MaloTMJ and muscle disorders (TMDs) are a group of conditions that cause pain and dysfunction in the TMJ and the muscles that control jaw movement . The mosOrthognathic surgery may have a beneficial effect on TMJ disorders and orofacial pain in subjects with preexisting signs and symptoms . HoweverThe influence of orthognathic surgery on the symptoms of TMD has been widely debated in the literature and among oral and maxillofacial surgeons, not only because of the possibility of improvement through the correction of deformities but also because of the possibility of symptom development. The aim of this study was to assess the frequency of orofacial , myalgia, and TMJ pain in orthognathic patients at a tertiary institution. Our hypothesis was as follows: orthognathic surgery may induce TMJ pain and myalgia in patients without pain before treatment as well as orofacial pains.Preoperative and follow-up data were collected from the records of consecutive orthognathic surgical patients between January 2014 and December 2016 with a minimum 1 year of follow-up after surgery. The primary outcome measure was the presence of self-reported nonodontogenic, neuropathic, or atypical orofacial pain and or pain in the TMJ and/or masticatory muscles  before the surgery and during follow-up. These self-reports were categorized by the assessor as an absence of pain, the presence of orofacial nonodontogenic pain, the presence of neuropathic or atypical orofacial pain, the presence of masticatory muscle and/or TMJ pain, normal sensation, and altered sensation . The diagnosis of pain and altered sensation was based primarily on a questionnaire, visual analog scale (VAS) pain score, history, and findings on physical examination .This retrospective study was approved by the Medical Ethical Committee of Leuven University Hospitals under number S57587.The bilateral sagittal split osteotomy (BSSO) surgical technique was described in detail elsewhere , 11. AllPain was assessed the same way in all patients. General information about the pain complaint was obtained using a pain questionnaire and complimentary interview. The questionnaire was designed to obtain as much basic information about the pain as possible within the limits of brevity, clarity, and self-administration. This information was completed during the interview. All patients were interviewed before orthognathic surgery and during the follow-up period by trained surgeons using a standardised protocol. The clinical pain assessment evaluated the presence or absence of pain. The subjective pain intensity present with the jaw at rest was assessed using a VAS. Subsequently, an increased pain response to voluntary opening and closing, as well as to moving the jaw anteriorly and laterally, was recorded. During subsequent assessments, joint tenderness was scored as either absent or present. The presence of muscle tenderness was assessed during mouth opening and closing and by digital palpation. Muscle tenderness was scored as being either present or absent. The presence or absence of pain and altered sensation was also noted. All patients with pain were managed postoperatively. Acute pain was managed with analgesia, such as nonsteroidal anti-inflammatory drugs (NSAIDs). Benzodiazepines were also used to manage acute TMJ pain accompanied by limited opening. Conservative modalities such as counseling, physical therapy, warmth application, and bilateral chewing and splint therapy were also applied. Osteosynthesis plate removal was done in patients with pain secondary to osteosynthesis plate. In patients with TMJ pain refractory to conservative treatment, arthroscopic surgery was advised.Information on patient age, gender, presence or absence of pain, presence of altered sensation, and type of surgery were recorded.The study included a total of 286 patients  aged 16–66 years (mean age 26.7 ± 12.3 years). During the 3-year study period, all patients who presented at the maxillofacial unit of UZ Leuven Hospital for orthognathic surgery were examined and followed up for a minimum of 1 year after surgery. One hundred twenty-two (42.66%) interventions required bimaxillary osteotomies, and 164 (57.34%) required bilateral sagittal split osteotomies (BSSOs). There was no report of altered sensation and muscle tenderness in any of the patients preoperatively, but 36 patients presented with pain associated with TMJ , 7 patients had orofacial nonodontogenic pain, and 3 patients complained of both TMJ and orofacial nonodontogenic pain. Preoperatively in most of the patients, the pain complaint apart from mild discomfort has little effect on their daily activity. The pain was reported to be intermittent in some patients, whereas others reported pain from time to time; the recorded VAS score ranged from 1 to 3 in patients with pain. The number of patients complaining of orofacial pain and TMJ pain decreased during follow-up . Of the An overview of patients with pain  before and during the follow-up period is presented in Fifty-one (17.8%) of the 286 orthognathic cases treated at our center over the 3-year period presented with pain 1 year after surgery; 3 (1.04%) were nerve related, 5 (1.75%) were due to osteosynthesis plates, 23 (8.04%) atypical odontalgia, and 30 (10.50%) were TMJ related. There are 28 patients  with new TMJ pain with an average age of 30 years. The common causes of nonodontogenic orofacial pain in the patients are shown in Pain was managed with medication such as nonsteroidal anti-inflammatory drugs, conservative modalities such as physical therapy, osteosynthesis plate removal, and arthroscopic surgery in TMJ pain refractory to conservative treatment.Our findings are in agreement with those reported by Dujoncquoy et al.  and WestOrthognathic surgery in the lower jaw strains the condylar area during surgical maneuvers in the ascending ramus. After orthognathic surgery, most patients heal without symptoms or signs at the TMJ, with a functional occlusion. However, reproducing the original condylar position is difficult, and too much pressure can be placed against the articular disc or an unfavorable condylar position can be created during osteotomy, which can worsen any preexisting TMJ symptoms or result in new ones . Hu et aTMJ pain can also be attributed to dysfunctional TMJ remodeling, which can be induced by systemic and local arthritis or trauma , 21 The We observed that the majority of patients with the new TMJ pain are women. Of the 28 new TMJ cases, 20 (71.4%) were female, which could be related to the previous findings by Aghabeigi et al. that women with an atypical psychological profile seem to be at increased risk of persistent postoperative TMJ pain after orthognathic treatment and open bite deformity [Osteotomy has been known to induce changes in the maxillary and mandibular teeth, buccal mucosa, palatal mucosa, and facial skin sensation. Though skin sensation tends to recover over time, even after direct damage to the sensory nerves, it may not completely recover to the presurgical condition. Postoperative orofacial pain includes a number of clinical problems involving the masticatory muscles or TMJ, including muscle spasms in the head, neck, and jaw and pain in the teeth, face, or jaw due to the extensive bone and muscle manipulation during orthognathic surgery .Neurological injuries during orthognathic surgery due to an exposed nerve together with disruption of the bony environment of the nerve may result in orofacial and/or musculoskeletal pain , 30, 31.Early diagnosis in conjunction with patient education is central to the management of orofacial and TMJ pain. The first line management of TMJ pain consists of conservative measures. Medications may be considered to manage the symptoms associated with pain in conjunction with patient education . MedicalAcute TMJ pain is managed effectively with simple analgesia, such as nonsteroidal anti-inflammatory drugs (NSAIDs) . BenzodiIn patients without preexisting TMJ complaints in whom orthognathic surgery resulted in TMJ complaints refractory to conservative treatment, arthroscopic surgery is advised, as it seems to be successful in all patients for both pain reduction and improvement of the maximal interincisal opening . HoweverApproximately 80% of the patients with orofacial pain and TMJ pain before orthognathic surgery were pain-free 1 year after orthognathic surgery. While 12.2% of patients with no preoperative orofacial pain and 9.3% without preoperative TMJ pain presented with pain 1 year after orthognathic surgery.


Introduction: Pain is an emotional experience. As a subjective feeling, it is associated with pathophysiological processes occurring in the central nervous system, which in turn may negatively affect the psychophysical function, cognitive abilities, level of functioning and quality of life.The Aim: The aim of the study was to assess orofacial and general pain location in patients with temporomandibular joint disorder—myofascial pain with referral.Materials and Methods: The study group consisted of 50 randomly selected, generally healthy people with complete natural dentition (37 women and 13 men) at the age of 23.36 ± 2.14 years, referred to the Department of Prosthodontics of the Medical University. All patients underwent clinical examination according to the Diagnostic Criteria for Temporomandibular Disorders (Axes I and II). The subjects were classified as people with myofascial pain with referral. The evaluation of severity of temporomandibular disorders was based on the Temporomandibular Disorder Pain Screener and the Graded Chronic Pain Scale. In order to assess orofacial and general pain location, a bodychart drawing of pain was used.Results: The study group indicated 40 different areas of the body affected by pain. 2–3 isolated pain locations were declared by a total of six subjects. One person identified 17 affected areas. Forty four people reported pain in at least four regions of the body. 70% of patients suffered from pain within the right masseter muscle. Pain of the left masseter muscle was noted in 68% of cases. Cervical ailments were reported by 56% of people. Pain of the left temporomandibular joint was observed in 68% of patients, and of the right one in 54%.Conclusion: The patients with myofascial pain with referral suffer from general ailments in different regions of the body. Only the frequency of pain in the right masseter muscle and right temporomandibular joint differed with respect to gender. The suggestion that the prevalence of pain in other areas of the body varies between men and women has not been confirmed. Due to a small sample size, such differences cannot be excluded. Further studies in this area are needed. Functional disorders of temporomandibular joints belong to the group of chronic facial disorders and affect about 10–15% of the total population . RepetitAccording to the definition of The International Study of Pain, pain is defined as an unpleasant sensory and emotional experience related to real or potential tissue damage or is described in terms of such damage , 9. PainThe aim of the study was to assess orofacial and general pain location in patients with temporomandibular joint disorder—myofascial pain with referral. The hypothesis was that the prevalence of pain in different areas of the body varies between men and women.The study group consisted of 50 randomly selected, generally healthy Caucasian people (37 women and 13 men) at the age of 23.36 ± 2.14 years , referred to the Department of Prosthodontics of the Medical University. All the participants were in the process of obtaining higher education, had never married and had at least good household income. The qualification criterion was the presence of pain in the cranio-facial and/or cranio-mandibular area at the level of 8 points in the VAS  on clinical examination. The evaluation was performed by a researcher who was also a dentist and physiotherapist. The patients represented complete natural dentition with the intercuspation corresponding to Class I, according to Angle, with no history of orthodontic treatment or retention status after its completion exceeding 3 years. Regarding the DC/TMD (Diagnostic Criteria for Temporomandibular Disorders), the subjects were classified as suffering from myofascial pain with referral pain –13. SixtPeople who had previous traumas and surgical procedures in the craniofacial area were excluded from participation. Cases affected by metabolic diseases and people whose medication or possible ailments could influence the functioning of masticatory muscles were also excluded. The group did not declare a history of physiotherapeutic treatment in the cranio-facial, cranio-mandibular, and/or cranio-cervical areas.Clinical examination including functional evaluation of temporomandibular joints and muscles of the masticatory system according to the DC/TMD – 13—axisTMD Pain Screener—axis I of the DC/TMD Graded Chronic Pain Scale version 2.0—axis II of the DC/TMD Pain drawing (Bodychart) , 2 to asAll patients underwent a thorough assessment. The proceedings covered:p < 0.05 were considered as statistically significant. With respect to Fisher's exact test, statistical post hoc power analysis was performed using G Power v. 3.1.9.4 Software (Germany). Power (1-ß) was calculated as the function of α, the population effect size and N.Statistical analysis was carried out using Statistica 12 Software   Supplem. A Chi-sThe project was carried out after obtaining consent from the Bioethical Commission of the Medical University No R-I-002/322/2016. The research was performed in accordance with the Helsinki Declaration of the World Association of Physicians and the principles of Correct Clinical Trial Guidance . Participation in the project was voluntary. Patients had obtained comprehensive information about the nature, scope of clinical activities and the course of the proceedings. At each stage, the respondents had the right to refuse to participate in the study, without any corresponding consequences. Participation in the study was preceded by the patient's written informed consent.The study involved 50 patients, 13 men and 37 women. Seventy percent of the people reported a possible occurrence of functional disorders of temporomandibular joints (TMD-PSc = 4–6) . In 15 pIn three patients from the study group, no significant chronic TMJ pain was found in the last 6 months with respect to GCPS v.2. . 30 60%.Seventy percent of patients suffered from pain within the right masseter muscle. Pain in the left masseter muscle was noted in 68% of cases. Cervical ailments were reported by 56% of participants. Pain of the temporomandibular joint was observed in 68% of patients on the left side and in 54% on the right side .2 = 4.162954, p = 0.04132)  . In this case, the test's power was slightly higher . 84.62% of men and 43.24% of women suffered from pain of the right temporomandibular joint  . Test's 5351020) . 92.31% 5351020) . A similar joint . With rear joint .The study group indicated 40 different areas of the body affected by pain . Up to tThe incidence of specific types of temporomandibular joint disorders with respect to the DC/TMD classification, depending on the studied population, is variable. John et al. stated that in a group of 416 women, 27.4% were cases of myofascial pain, 21.4% subjects had myofascial pain associated with mobility restriction of the mandible, 44.2% were patients with dislocation of the disc with the possibility of reduction, and 6.3% cases were the displacement of the disc without reduction . ArthralIn the presented study it was found that the potential presence of functional disorders of temporomandibular joints can affect up to 70% of patients, including 26 women and 9 men . The remThe results of this study obtained on the basis of the bodychart reflect the characteristic profile of myofascial disorders associated with referred pain , 2. AtteIn our study, the patients were a homogeneous group of people with myofascial pain with pain referral. With regard to the bodychart, only two people indicated ailments limited to two places of occurrence . Forty eParticular attention should be paid to pain in the cervical, thoracic and lumbar spine observed in ± 50% of the subjects  Figures, 2. The Bogduk et al. emphasize the role of convergence between cervical and trigeminal afferents in the trigeminocervical nucleus. This author indicates that nociceptive afferents from C1, C2, and C3 spinal nerves converge with the first division of the trigeminal nerve, which mediates referred pain from the neck to the head  .Pain from the cervical zygapophysial joints, which has constant segment patterns, must also be mentioned. Pain within zygapophysial joints at the C2-C3 level is referred toward the front of the head. Pain from C3-C4 and C4-C5 remains within the posterior part of the neck. A typical location of spreading pain from C5-C6 is supraspinous fossa of the scapula. C6-C7 generates spreading pain caudally over the scapula .Pedroni et al. noted that most frequently the pain area indicated by TMD patients was the cervical spine (92.85%) and scapular region (50%). The third most commonly observed location was TMJ (42.85%), followed by masseter muscle (35.71%), temporal muscle (21.42%), and frontal region (28.57%) .Wright et al. indicated the significance of postural re-education in reducing pain in temporomandibular joints, as well as in attempts to improve the extent of mouth opening . KomiyamBased on the presented results, the bodychart appears to be an extremely useful diagnostic screening tool. It constitutes a part of the comprehensive biopsychosocial assessment as well as the way of programming therapy in patients with temporomandibular joint disorder .According to the chronic pain scale GCPS v 2.0, grade I of complaints was observed in 60% of the subjects . In the It is also interesting to note that in the case of patients with musculoskeletal pain and temporomandibular joint disorders, chronic pain is the cause of limited activity in everyday life, as well as psychosocial dysfunction –32. At tThe results obtained with regard to GCPS v 2.0 differed from those listed in the literature and are most likely determined by the homogeneity of the study group, only including cases of myofascial pain with referral. According to Reiter et al., study results are often conditioned by the social context, ethnic origin, culture, personality traits, as well as the level of intelligence .In turn, in the studies by Olivo et al. carried out in a group of 45 women aged 18–50 years old with temporomandibular joints dysfunction with myogenic etiology, grade I of chronic pain intensity was found in 19 people with respect to the GCPS scale, grades II and IV only in one case, respectively, and grade III in 24 subjects . On the Our study was designed to induce reflection of clinicians treating patients with temporomandibular joint disorders. Pain locations indicated the multifaceted nature of complaints in people who potentially declared good health. The bodychart revealed the size of the patients' problems. Many areas of complaints may suggest processing disorders and central sensitization. Pain drawings emphasized the essence of the biopsychological component in this group of patients and the need to cooperate in an interdisciplinary team.Standardized procedures (DC/TMD protocol) allow the study to be repeated in similar research projects with the observation of comparable findings. Clear documentation of “Pain Drawing” allows other researchers using the DC/TMD protocol to assess the validity of the study results. The use of the Pain Drawing (DC/TMD protocol) emphasizes the need for holistic treatment in patients with craniofacial disorders. The bodychart reflects the specific profile of myofascial pain with referral. It is possible to estimate the cost and benefits of clinical prosthetic and physiotherapeutic procedures. In each case it is possible to determine the possible pattern of descending or ascending hereto or unilateral disorders corresponding to the craniomandibular dysfunction.Self-reported information obtained from the bodychart may be inaccurate or incomplete. The clinical protocol for examining patients in accordance with the guidelines of DC/TMD requires precision and is time-consuming. Due to extensive DC/TMD instruments, it is not possible to present all data in one study, which may result in the omission of information that is key for the subject's case. Some information is difficult to receive through DC/TMD protocol, particularly on sensitive topics such as role of dura mater in TMJ disorders. The DC/TMD protocol does not include a clinical examination of many muscles affecting the mobility of the mandible. Interdisciplinary cooperation with physiotherapists is necessary. Research methods are inflexible, and the protocol is imposed in advance. The expanded DC/TMD questionnaire (Axes I and II) may alienate respondents. The bodychart results may mask or ignore underlying structural causes or sources of pain. Due to the small research group, further studies in this area are needed.The bodychart is an effective research and clinical tool which allows one to reflect unconscious pain. The patients with myofascial pain with referral suffer from general ailments in different regions of the body. Only the frequency of pain of the right masseter muscle and right temporomandibular joint differed with respect to gender. The suggestion that the prevalence of pain in other areas of the body varies between men and women has not been confirmed. Due to the small sample size, such differences cannot be excluded. Further studies in this area are needed.The project was carried out after obtaining the consent of the Bioethical Commission of the Medical University of Białystok No R-I-002/322/2016. The research was performed in accordance with the Helsinki Declaration of the World Association of Physicians and the principles of Correct Clinical Trial Guidance . Participation in the project was voluntary. Patients had obtained comprehensive information about the nature, scope of clinical activities and the course of the proceedings. At each stage, the respondents had the right to refuse to participate in the study, without any corresponding consequences. Participation in the study was preceded by a patient's written consent.JK conceived and planned the study. JK and KS carried out the experiment. JK and KS contributed to sample preparation. TS contributed to the interpretation of the results. JK and KS took the lead in writing the manuscript. TS supervised the project. All authors discussed the results and contributed to manuscript revision, read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The study will try to give new insights into the mechanism of SCS action and the role of IFN-γ and other cytokines in neuropathic pain (NP) development.  We investigated the influence of spinal cord stimulation (SCS) on IFN-group 0 consisted of 24 FBSS patients qualified to SCS therapy, group 1 included 17 patients who were one month after implantation, group 2 featured 12 patients who were 3 months after the implantation, and group C (the control group) with no NP. Clinical status was assessed with the use of Numeric Rating Scale (NRS), the Pain Rating Index of McGill Pain Questionnaire (SF-MPQ), the Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The plasma concentrations of IFN-γ were ascertained by an immunoenzymatic method.  Clinical and biochemical assessment was conducted in four groups of patients: γ. Similarly, a significantly higher level of TNF-α and significantly lower level of IL-10 in FBSS patients than controls were observed. The significant differences were not observed between SCS patients 3 months after the procedure and controls' serum level of IFN-γ and other cytokines. We noticed a positive correlation between IFN-γ concentration with NRS back value before SCS and positive correlation between IFN-γ concentration after SCS with NRS leg value before SCS. Higher IFN-γ concentrations accompanied higher NRS values. Levels of TGF-β and IL-10 may correlate with physical ability and depressive behavior.  We found a significant difference between the patients before SCS and controls' serum level of IFN-γ may be recognized as an occasional pain factor because of its significantly higher level in FBSS patients versus controls and higher IFN-γ value accompanying higher pain intensity. SCS did not influence serum cytokine levels significantly. Serum concentration of IFN- Failed back surgery syndrome (FBSS) is one of the unsolved treatment problems that occur after spinal surgery and it is also believed to be one of frequent causes of neuropathic pain. Patients with FBSS often suffer from epidural, intraneural, or perineural fibrosis and scar tissue. They usually do not respond to classic spinal surgery. The treatment of chronic neuropathic pain which results from FBSS is difficult to manage because of poor understanding of pain mechanisms and difficulties with objective assessment of pain intensity. Recently, spinal cord stimulation (SCS) improving quality of life and patient ability has been recognized as one of the most useful methods for neuropathic pain treatment , 2. Detaγ, TNF-α, IL-1β, and IL-6 associated with the presence of pain and anti-inflammatory cytokines such as TGF-β and IL-10 associated with pain relief [α and IL-6 are upregulated in the animal models [β produces pain behavior in rats [β reduces pain, secondary to CCI in rats [The main role played in the formation and maintenance of neuropathic pain (NP) is nerve irritation and inflammation which produce changes in the serum expression of cytokines . Cytokinn relief –11. Cyton relief . After nl models –20. The  in rats , 22. Par in rats , 24.γ. Proinflammatory cytokines such as IFN-γ produced by the immune and glial cells are believed to especially modulate neuronal transmission and play a role in neuropathic pain feeling. After nerve injury, IFN-γ is upregulated in the rat dorsal horn and cooperates in neuropathic pain induction and maintenance [γ induces a long-lasting depolarization of inhibitory circuits sensitizing at the same time the ascending pain tracts [γ may inhibit glutamate receptor 1- (GluR1-) positive interneurons in the dorsal horns of the spinal cord [γ receptor forms a special receptor complex with the AMPA receptor subunit GluR1 [γ and other cytokines in SCS.In our interest is especially IFN-ntenance –27. IFN-n tracts . Neuron-n tracts , 30. In nal cord , 31, 32.γ, and other cytokine serum levels.The aim of this study is to observe if SCS influences analgesic response, IFN-A total of 24 patients included in the study  were admitted to the Department of Neurosurgery of Medical University of Lublin in Poland and underwent SCS for the management of pain resulting from FBSS. Magnetic resonance imaging was used to choose and verify patients with FBSS. Cases such as recurrent disc herniations, spinal stenosis or instability, spinal tumors, and infections were excluded. Coexisting neurologic and psychiatric diseases, systemic and inflammatory diseases, use of corticosteroids, tumors, active infections, severe depression, hypochondriac behavior, and alcoholic abuse belonged to the additional exclusion criteria.The patients have been implanted with 16 electrodes of Medtronic equipment. The surgical operation was performed under general anesthesia. The implantation of paddle was performed by laminectomy at the Th10-Th12 level. The procedures consisted of two phases. The trial period usually lasted for 3 to 4 days with the use of the external trial stimulator. Then, the decision about implantation of an impulse generator (IPG) was undertaken when more than 50% pain reduction was obtained in the NRS. 17 patients, out of the 24 primary qualified, found SCS as enough satisfactory treatment. The opioids were used to ameliorate pain caused by the implantation procedure during the postoperative period (2-3 days). The SCS parameters were recorded which are shown in All patients underwent standard physical and neurological examination three times: prior to surgery, one month after, and three months after the procedure. Motor deficits, reflexes dysfunctions, and straight leg-raising test were evaluated. Patients filled in a questionnaire about the intensity and duration of pain according to the Numeric Rating Scale (NRS), questionnaire about neuropathic pain by the Pain Rating Index of Short-Form McGill Pain Questionnaire (SF-MPQ), Oswestry Disability Index (ODI), and Beck Depression Inventory (BDI). The individual SCS parameters for each patient to achieve analgesia were recorded. The results were compared with outcomes of 24 healthy volunteers, used as controls, from the community hospital without previous back and sciatica pain. The 7 patients, out of the 24 primary qualified group, did not have implantation because of coexistence of medical conditions which excluded under general anesthesia, withdrawal of written consent for operation, or lack of efficacy of SCS during the trial period. The patients from group 1 were evaluated 1 month after the operation. The 5 patients missed the control visit so 12 patients from group 1 consisted in group 2, which was also evaluated after 3 months since operation. The characteristic of patient groups is presented in g for 15 minutes. The serum samples were frozen at -80°C until analyzed.Blood samples were collected just prior to surgery, one month after, and three months after. Five milliliters of venous blood was collected in the morning and immediately centrifuged at 4000 γ, IL-1β, IL-6, TNF-α, IL-10, and TGF-β Quantikine ELISA Kit, R&D Systems) was used for a quantitative determination of human IFN-γ in plasma samples. We followed the protocol recommended by the manufacturer. The ELISA Reader Victor  was used in the procedure. Samples were assayed in duplicate.A commercial enzyme-linked immunosorbent assay (ELISA) kit  were used to assess the effect size. The Spearman rank correlation coefficient (rs) was applied to assess the relationships between variables. The level of significance was α = 0, 05.Statistical analysis was performed with the use of IBM SPSS Statistics (version 24.0). Data was reported as the minimum, maximum, and mean values as well as standard deviation. For intergroup comparisons, we used Student's M = 55, 87 . Among them, there were 13 female (F) patients and 11 men (M), and 13 were physical workers. In the past, they were operated on several times, average 2,8 . The average time of pain duration before operation was M = 130 months (SD = 114). The patients of group 0 were assessed just before the performance of the procedure of SCS implantation. Group 1 consisted of 17  of these patients who were qualified for implantation of SCS. They were with mean age M = 56, 24 . The 59 percent of them worked as physical workers. The patients were operated on several times at an average of 3 times . The mean time of pain duration was 146 months (SD = 126). We also distinguished group 2 consisting of 12 patients  from group 1 which were additionally evaluated 3 months after operation. Group 2 was smaller than group 1 because 5 patients did not come for follow-up visit. The control group included 24 healthy volunteers from the community hospital without previous back and sciatica pain (see Our research was conducted in 4 groups of patients. Group 0 consisted of 24 patients with neuropathic pain because of FBSS (FBSS group) within the mean age pain see .t10 = 3,573; p = 0,003; effect size d = 0, 99); and after 90 days, the mean NRS of the back M = 2, 55  . Similarly, we observed a significant decrease of lower limb pain—before SCS, the mean NRS of the leg M = 7, 12 ; after 30 days, the mean NRS of the leg M = 5, 38  ; and 90 days after, the mean NRS of the leg M = 3, 35; ,  ; after 30 days, the mean NRS of the back = 3, 82  (063) see .t12 = 2,263; p = 0,021, effect size d = 0, 80). Before the procedure, the mean ODI M = 31, 47 points  and after 30 days, the ODI M = 26, 15 points . The results after 90 days did not change significantly . Relationships between BDI scores were not significant  and control  serum level of IFN-γ . Significant differences were not reported between SCS patients after 3 months and control serum level of IFN-γ ; after 30 days, the mean level was 14,33 ; and after 90 days, the mean level was 12,12  , group 1 vs. group 2  (see IFN-136) see .γ concentration with NRS back value  before SCS and positive correlation between IFN-γ concentration after SCS with NRS leg value  before SCS. Higher IFN-γ concentrations accompanied higher NRS values (see We noticed a positive correlation between IFN-lues see .n = 24) and the control group (Student's parametric significance t-test for two averages and nonparametric Mann-Whitney's U test) showed a significant difference only in the IL-10 level  and TNF-α level . In the FBSS group, the average level of IL-10 was M = 9.14 (SD = 4.69), while in the control group M = 17.87 (SD = 10.50). On the contrary, patients with FBSS had higher levels of TNF-αM = 71.49 (SD = 83.04) than those in the control group M = 28.08 (SD = 21.48), whereas the groups did not significantly differ in IL-1β, IL-6, and TGF-β levels. The relationship between the occurrence of neuropathic pain and the level of IL-10 is high and moderate with regard to the TNF-α levels , similarly to the level of IL-10 . A month after SCS, patients showed higher TGF-β levels than those in the control group .But interestingly, in the follow-up study, 1 month after SCS, significant differences in IL-1β and IL-10 in patients was still significantly lower , while the level of TGF was higher   see .β and clinical outcomes were the most interesting. The level of TGF-β before surgery correlates negatively with the NRS leg scale results obtained in the follow-up one month after SCS  and with the ODI scale results in the follow-up study 3 months after SCS —a higher TGF-β level before surgery correlates with less pain in the leg area a month after SCS and better functioning at 3 months after SCS.Correlations concerning TGF-β, measured 3 months after surgery, correlates negatively with the NRS leg scale results obtained in the follow-up study one month after SCS  and with the results of the ODI scale in the follow-up month after SCS  and 3 months after SCS —a higher TGF-β level measured 3 months after SCS correlates with less pain in the leg area a month after SCS and better ability a month and 3 months after SCS.The level of TGF-β, measured 3 months after surgery, correlates negatively with BDI depression scale scores obtained in the follow-up study a month after SCS —higher intensity of depressive symptoms in BDI one month after surgery correlates with lower TGF-β level in measurement 3 months after SCS.The level of TGF-rs = −0.608; p = 0.036) and the severity of depressive symptoms in the BDI scale 3 months after SCS —a higher level of IL-10 before surgery correlates with lower ODI scores  and less severe depressive symptoms at 3 months after SCS.The level of IL-10, before surgery, correlates negatively with the results of the ODI scale obtained in the follow-up study 3 months after SCS .There were no significant correlations between the TNF-β and IL-6 were nonconclusive.Correlations between the results of clinical scales and levels of IL-1α are significantly upregulated during chronic pain [γ concentrations in the human serum before and after SCS treatment. There are not any significant differences between IFN-γ serum concentrations before and after SCS. Nevertheless, it is interesting that higher IFN-γ concentrations accompany higher NRS scores. There are numerous reports about spontaneous pain occurring as a side effect of IFN-γ therapy in oncology [γ) is a proinflammatory cytokine and important modulator of central and peripheral immune response and additionally plays a role in the pathogenesis of neuropathic pain [γ serum level in FBSS patients is significantly higher than that in the control group, although Koch et al. reported no relationship between plasma IFN-γ and pain intensity [γ may contribute to the pathogenesis of nociceptive activity and pain behavior in acute lumbar radicular pain [γ plays an important role as one of the factors leading to central sensitization, which results in neuropathic pain. [γ serum level differs from controls, and it is important to seek possibilities of objective assessment of SCS action.Since the 1980s, SCS therapy has been available for patients suffering from neuropathic pain related to FBSS . More thnic pain –39. To ooncology . Interfehic pain . It is vntensity . Moen etlar pain . Studiesic pain. . So the β, IL-6, and TNF-α are significantly upregulated during chronic neuropathic pain and anti-inflammatory cytokines such as IL-10 are significantly downregulated during chronic neuropathic pain state.It is known that serum levels of proinflammatory cytokines such as IL-1α serum level in FBSS patients was significantly higher than that in the control group. So FBSS patients estimated that cytokine serum levels differ from controls. The role of TNF-α is complex. During NP induced by nerve injury, the TNF-α action as recognized acts at different levels of the nervous system. TNF-α plays a role at the site of nerve injury, at the dorsal root ganglion, at the dorsal horn of the spinal cord, and at the brain [α is found peripherally during nerve damage in CCI animal models of neuropathic pain [β, IL-6, and TNF-α has been observed during induced discogenic pain in animal models [α and IL-6 may be significantly upregulated during chronic pain [α may involve TNF-α-apoptosis-caspase [+ ion conductance is increased in a non-voltage-gated fashion leading to neuronal hyperexcitability [α antagonists depends on the type of neuropathic pain and is less effective in rat disc herniation models than in diabetic origin [It is very interesting that the TNF-he brain . Many sthic pain –16. The l models . Additionic pain –39. A po-caspase . Membrantability . Additioc origin , 49.α-expressing cells and attenuates thermal hypersensitivity after CCI [The value of IL-10 was significantly lower than in the control group and did not change after SCS. It was observed that the IL-10 level correlates negatively with ODI and BDI scores. So a higher level of IL-10 accompanies better physical ability and less depressive behavior. The serum level of anti-inflammatory cytokine such as IL-10 was lower in patients with complex regional pain syndrome (CRPS) than in the controls . The IL-fter CCI .β, after SCS, decreases significantly and TGF-β significantly increases when compared to the results in controls.There were no significant differences in cytokine serum concentrations in the FBSS group before and after SCS. However, IL-1β, 1 and 3 months after SCS, were lower than those before SCS but not significantly. Nevertheless, IL-1β levels 1 and 3 months after SCS were significantly lower than in controls. Elevated levels of IL-1β have been found in rats with chronic neuropathic pain, both peripherally and in the brain scan [β administration induces pain behavior in rats [β induces central cyclooxygenase-2 (COX-2) upregulation, which results in an increase in the synthesis of PGE-2 in spinal cord neurons and the brain [It was observed that the levels of IL-ain scan –56. The  in rats , 22. Pos in rats –59. Morehe brain .The values of IL-6 in the FBSS group and controls did not differ significantly as the values of IL-6 after SCS. The IL-6 dual nature is known. It is perceived as proinflammatory and anti-inflammatory cytokine. There are several human studies with different results. Some studies showed elevated IL-6 in a patient with herniated discs , 62. Aniβ increases after SCS but not significantly. It is interesting that the TGF-β serum level after SCS was significantly higher than in controls before SCS and 3 months after and correlates negatively with NRS leg, ODI, and BDI scores. A higher TGF-β level characterizes less leg pain, better physical ability, and less depressive behavior. Intrathecal administration of TGF-β reduces pain secondary to CCI in the animal model [β secretion reducing CCI-related neuropathic pain [The value of TGF-al model , 66. It hic pain .γ and other cytokine serum levels before and after implantation as well as when compared to healthy controls. A limited group of patients results from the homogeneity of a group (only FBSS) and exclusion of patients with serious comorbidities. It is not possible to exclude that surgery procedure itself had any influence on observed changes [γ and other cytokine serum levels is not obvious. Further explorations are needed to explain what is the real neuroimmune target for SCS therapy.The search for neuroimmune mediators in the serum may be safer and more useful for the monitoring of treatment. Cytokines are signaling proteins mediating activation, differentiation, and proliferation of immune cells and may play a role in chronic pain threshold. Cytokine synthesis is prompt and their actions are often localized with a short half-life period . Pivotal changes . A signiγ and other cytokines as neuroimmune factors in the pathophysiology of neuropathic pain from FBSS. Serum concentration of IFN-γ may be recognized as an occasional pain factor—significantly higher level in FBSS patients versus controls and higher IFN-γ value accompanying higher pain intensity. Levels of TGF-β and IL-10 may correlate with physical ability and depressive behavior. This study research does not confirm directly the relationship between SCS and IFN-γ and other cytokine serum levels but adds additional clinical light for cytokine action in neuropathic pain in FBSS patients. Further investigations for SCS influence on serum cytokines are needed.Balance between proinflammatory and anti-inflammatory cytokines may play a role in neuropathic pain during FBSS. SCS did not influence serum cytokine levels significantly. Our data supports an important role for IFN-


Radiofrequency thermocoagulation (RFT) through the foramen rotundum has emerged as an alternative for treatment of isolated V2 trigeminal neuralgia. But puncture of the foramen rotundum is difficult and time-consuming. In current study, we introduced the application of a computer-assisted design (CAD) template to guide foramen rotundum cannulation. Meanwhile, we assessed its safety and efficacy in the treatment of isolated V2 trigeminal neuralgia. n=17, puncture with a CAD template) and control group  according to the puncture method used. The puncture times, duration of puncture, and duration of operation were collected. The outcome of pain remission was evaluated utilizing the Barrow Neurological Institute's (BNI) pain score. Complications and recurrence of pain were also recorded. Data were compared between groups.  From November 2015 to August 2017, thirty-eight patients with isolated V2 trigeminal neuralgia were treated with computed tomography- (CT-) guided RFT through the foramen rotundum in our institution. All cases were reviewed, and patients were divided into the experimental group  postoperatively. At four follow-up points , there was no significant difference in good pain relief rate between the two groups. Meanwhile, no significant difference was found in complications.  CAD template is a safe and precise navigation instrument for RFT treatment of isolated V2 trigeminal neuralgia via the foramen rotundum. Therefore, this novel tool is worthy of clinical promotion. The idiopathic trigeminal neuralgia (ITN) is a common clinical condition characterized by recurrent, paroxysmal, and tortuous facial pain occurring in one or more divisions of the trigeminal nerve , 2. As rBlind puncture could cause serious complications. Huang et al.  first inIn recent years, the computer-assisted design (CAD) technique has been widely used for individualized guidance in the process of pedicle screw insertion , 19, denn=17, puncture with a CAD template) and control group  according to the puncture method used in procedure. The demographic information of patients is depicted in This study was approved by the review board of Nanjing Drum Tower Hospital 201810401). From November 2015 to August 2017, thirty-eight patients diagnosed with idiopathic V2 trigeminal neuralgia received RFT through the foramen rotundum in our institution. The diagnosis was based on the beta diagnostic criteria for ITN  [810401. FManufacture of a CAD template requires slice CT  scanning of the head . CT images (DICOM format) were imported into Mimics software , and three-dimensional images of the head were reconstructed. We set the target at the external opening of FR and simulate the puncture trajectory  through the pterygopalatine fossa . The traThe template consists of two parts: a support bracket and a guide cannula. The support bracket was individually designed to fit patient's face perfectly to ensure stability. Meanwhile, when the patient's nose and zygomatic process were used as support structures, such a bracket should be large enough to cover these parts. The guide cannula was designed along a confirmed trajectory with an inner diameter slightly larger than the puncture needle. The personalized template of the designs was exported (in the format of STL) and imported into a three-dimensional printing (3D) printer  for manufacture .The CAD template was disinfected prior to clinical use. After the process of skin preparation and draping, the template was placed on the patient's face stably, and local anesthesia was given with 2% lidocaine via a guide cannula. Then, a 2 mm tip 22G radiofrequency needle was punctured to the measured depth through a guide cannula. A CT scan was conducted to confirm the correct cannulation before the routine treatment process .In the control group, the cannulation of the foramen rotundum was conducted with the traditional method under the guidance of CT . A lead All medical history, surgery records, and follow-up records of these patients were obtained from the clinical information system. Images and the scanning time were collected from the picture archiving and communication system. The calculation includes duration of puncture (from the start of operation to the end of last scanning), duration of operation (from the start of skin preparation to the end of the RFT), and puncture times . We also assessed the therapy effectiveness using Barrow Neurological Institute's (BNI) score at each follow-up point . Pain relief was classified as good  and poor  . Complict-test was utilized to analyze differences in age, duration of disease, pain intensity, puncture times, and duration of puncture and operation. The chi-square test was utilized to analyze differences in gender, affected side, pain relief, and incidence of complications between groups. Statistically significant difference was identified by an exact P value < 0.05.SPSS, version 23.0  was used for the statistical analyses. Student's P < 0.05). Mean duration of puncture and operation in the experimental group was also shorter than that of the control group   completed the cannulation of the foramen rotundum with one attempt. The remaining 2 cases (11.76%) took two tries to finish the puncture process. Only 4 patients in the control group underwent one-time success, and the average puncture times was 2.9 ± 1.1. The rate of one-time successful cannulation in the experiment was obviously higher than that in the control group ( < 0.05) .All patients in both groups experienced good pain remission (BNI Class I or BNI Class II) postoperatively. The good pain relief rates of the experimental group at 7 days, 3 months, 6 months, and 12 months were 100%, 100%, 94.1%, and 88.2%. Two patients experienced recurrence of pain (BNI Class IV), respectively, five and ten months after operation. The rates of good pain relief at each follow-up point in the control group were 100%, 100%, 90.5%, and 85.7%, respectively. Three patients experienced pain recurrence (BNI Class IV), respectively at five, six, and nine months after operation. Five patients subsequently received repeated percutaneous RFT through the foramen rotundum and got satisfied postoperative pain relief (BNI Class I).P=0.196). No other serious complications were found.All patients experienced mild facial numbness in the second branch of the trigeminal nerve immediately after surgery, and this symptom gradually subsided within one to three months. There were 5 cases of facial hematomas in the control group and 1 case in the experimental group. Ice compress was used to attenuate this complication. There was no significant difference in facial hematomas incidence between the groups  , the incHowever, the opening of the FR is small, and its orientation is rarely parallel to the cannulation trajectory, making the puncture process more difficult than the cannulation of the foramen ovale . Huang eIn recent years, with the development of CAD and rapid prototyping technique, an individualized template has been found applied in a variety of puncture procedures including denture implantation , 27, verIn our study, all patients received satisfactory pain relief immediately after surgery. All patients experienced numbness in the second branch of the trigeminal nerve, and this symptom gradually subsided within one to three months. At the four follow-up points, there was no significant difference in good pain relief rates between the two groups. During the 12-month follow-up period, two patients in the experimental group and three in the control group experienced pain recurrence (BNI Class IV). Both patients achieved good pain remission after repeated RFT treatment through FR. Our results demonstrated that the efficiency of the RFT was stable as long as the needle tip was accurately placed at the external opening of the foramen rotundum. Wan et al.  found a The preponderant complication is facial hematomas. The incidence of facial hematomas in the control group was higher than that in the experimental group. Even though the difference was not statistically significant, we believe that it could be increasingly obvious as the sample increases. In our research, we did not find other serious complications including intracranial bleeding, puncture injury of the V1 or V3 branch, and even cerebrospinal fluid leakage, as reported in previous research works , 23, 32.CAD template shows great potential in enhancing the safety and accuracy ablation of RFT for isolated V2 trigeminal neuralgia. This novel instrument deserves the attention of pain physicians, especially in resolving complex foramen rotundum cannulation. Meanwhile, prospective clinical studies are needed on a larger number of samples to further confirm our results.


While pain is a common symptom in JIA patients, it remains unclear why some JIA patients develop ongoing or persistent pain. Complex clinical and social settings confound analysis of individual factors that may contribute to this pain. To address this, we first undertook a retrospective analysis of pain reports in a JIA patient cohort with the aim of identifying potential factors contributing to persistent pain. We then carried out an experimental laboratory study, using joint inflammatory pain behaviour in rodents, to validate the role of these factors in the onset of persistent pain under controlled conditions.Patients: Retrospective analysis of anonymised pain visual analogue scale (VAS) scores and accompanying clinical scores from 97 JIA patients aged 13–19 (mean: 16.40 ± 1.21) collected over 50 weeks. Rats: Experimental study of pain behaviour following intra-articular microinjection of complete Freund’s adjuvant (CFA) in adolescents (n = 25) and young adults (n = 43). Some animals (n = 21) had been previously exposed to joint inflammation in infancy or adolescence.Patients: Cluster analysis of patient pain VAS scores revealed three trajectories over 50 weeks: consistently low pain (n = 45), variable pain (n = 30) and persistently high pain (n = 22). Number of actively inflamed joints did not differ in the three groups. High pain at a single visit correlated with greater physician global assessment of disease activity, while a high pain trajectory over 50 weeks was associated with more limited joints but fewer actively inflamed joints. Rats: Rodents administered ankle joint CFA also exhibit low, medium and high joint pain sensitivities, independent of joint inflammation. Prolonged inflammatory pain behaviour was associated with high background pain sensitivity, following joint inflammation at an earlier stage in life.Both JIA patients and rodents differ in their individual pain sensitivity independent of the concurrent joint inflammation. Using experimental animal models allows us to isolate physiological factors underlying these differences, independently of social or clinical factors. The results suggest that a history of prior arthritic activity/joint inflammation may contribute to high pain sensitivity in adolescents with JIA.The online version of this article (10.1186/s12969-019-0360-3) contains supplementary material, which is available to authorized users. Juvenile idiopathic arthritis (JIA) is a heterogenous group of inflammatory arthritides affecting 1 in 1000 children in the UK –4 and paRecent studies show that only a subset of children with JIA 10–20%) develop persistent pain over 5 years from disease onset –10. Thes–20% deveUnderstanding the factors determining pain trajectory is crucial to furthering our understanding of JIA pain, but assessing the relative contribution of individual factors is extremely difficult in patient cohorts. Animals models provide an alternative approach – allowing contributing factors to be assessed in a controlled setting . Age appIn the first part of this study we have undertaken a retrospective analysis of pain reports in a JIA patient cohort with the aim of identifying biological factors that explain reports of persistent pain. In the second part we have used an experimental rodent model of joint inflammatory pain, to validate the role of these factors in determining pain sensitivity in these models.This part of the study is a retrospective analysis of data collected from patients with JIA and their physicians at clinic visits to University College London Hospital. The data follows an observational study design examining factors influencing pain in a cross-section of adolescents with JIA.Study participants attended routine clinical appointments at University College London Hospital between 2014 and 2018. At each appointment, patients completed a questionnaire which included the 10 cm pain Visual Analogue Scale (VAS), the Childhood Health Assessment Questionnaire (CHAQ) and a 10 cm patient general evaluation VAS (PGE). Concurrently, physicians completed a 10 cm physician global assessment VAS (PGA) and recorded the number of active (inflamed), swollen and limited joints. Patient characteristics  were noted for each appointment. All data was anonymised prior to patient selection and statistical analysis.Disease activity markers erythrocyte sedimentation rate and c-reactive protein levels were only available for 43% of clinic visits because blood sampling is only routine practice in patients receiving disease-modifying antirheumatic drugs (DMARDs) or biologics and because the data was only available if blood sampling coincided with a clinic visit. As such these factors could not be included in the analysis without losing statistical power. Information on disease markers for each pain trajectory is available in Additional file Physician reported outcomes are drawn from evaluations made during clinical appointments. Several rheumatologists contributed to the data with an agreed consensus between physicians. Intra-investigator variation was not assessed due to the retrospective nature of this study.In total, 282 patients with JIA attended the clinic for at least 1 year. Sixteen were excluded due to a change to a non-JIA diagnosis. The remaining patients made 1714 clinic visits overall with varying intervals between appointments. Completion of the patient questionnaire varied (67.3% completed). Physician-reported measures (PGA and joint counts) were reported at 80.4% of visits. Patient characteristics are shown in Table Only patients with 3 pain VAS scores obtained at 25 ± 7 week intervals were included in the analysis. Data collection was opportunistic, leading to the following exclusions: 60 patients with an insufficient number of pain VAS scores, 104 patients with incorrect time intervals between visits, and 5 patients due to missing baseline variables. The exclusion criteria are shown in Fig. In total, 97 patients were included in this analysis Fig. , aged 13Analyses were performed using SPSS, version 25. Patient pain trajectories were identified using hierarchical cluster analysis. Distinctions between trajectories were identified using repeated measures two-way ANOVA with Bonferroni post-hoc analysis. Characteristics of patients with each trajectory type were compared using either one-way ANOVA or Chi-Square test, depending on the type of data.The influence of current arthritic activity on pain was determined using linear regression assessing the correlation of physician-reported measures with pain at a single clinic visit. PGA and the number of active joints for each trajectory type were also compared using one-way ANOVA with Bonferroni post-hoc analysis.Factors associated with each trajectory type in patients were identified using multinomial logistic regression. Physician-reported measures collected at study onset and patient characteristics were included in this analysis. In addition, the association of active, swollen or limited joints (or a combination of the three) with trajectory type was examined using Fisher’s Exact test.This part of the study examined factors, highlighted in the analysis of patient data, in an experimental animal model of monoarthritic pain. This allowed us to assess their contribution to inflammatory pain sensitivity in the absence of confounding factors.oc, 12h light-dark cycle) with unlimited food and water. Handling and maternal separation of pups were kept to a minimum and animals were exposed to the same standard caging, handling and diet throughout.Animal experiments were performed under a project license from the UK Home Office. Male and female Sprague-Dawley rats were bred and maintained in-house at UCL under standard conditions . Control animals received CFA for the first time at P40 (n = 12/sex) or saline (n = 12/sex). Three animals receiving CFA twice were removed from the study due to excessive joint inflammation and pain behaviour. Two animals were excluded due to no pain behaviour post-CFA.Monoarthritis was induced by a microinjection of complete Freund’s adjuvant  into the intraarticular space of the left ankle joint. Animals were anaesthetised with isoflurane and a 30-gauge needle attached to a 100 μl Hamilton syringe was inserted into the ankle joint from the posterior lateral aspect. The minimum volume of CFA required to produce acute arthritic inflammation was administered, namely 2, 10, or 20 μl CFA for animals aged postnatal day (P)8, P21 and P40 respectively . Control animals were administered sterile saline using the same procedure. In some animals, intraarticular injections of CFA were administered at two ages: either P8 or P21 and again at P40  and regularly (every 1–4 days) up to 24 days post-injection. Calibrated von Frey hairs were applied to the paw and the mechanical withdrawal threshold was determined using the up-down method as described elsewhere . ThreshoHindlimb weight bearing was measured using an incapacitance meter (Churchill Electronic Services) which measures the weight supported by each hindlimb of a stationary animal. Three readings collected over 1 min were averaged and the weight borne by the ipsilateral limb was expressed as a percentage of the weight borne across both hindlimbs.Ankle joint diameter was assessed as an indicator of the extent of joint inflammation. This was measured using callipers while the animal was standing. The joint was measured across the widest point–the malleoli produced by the fibula and tibia. Joint diameters were transformed into a percentage change from baseline.Analyses were performed using SPSS, version 25. Sensitivities to inflammatory pain were identified using hierarchical cluster analysis. Distinctions between different sensitivities were identified using repeated measures two-way ANOVA with Bonferroni post-hoc analysis. The distribution of male and females across pain sensitivities was examined using a Chi-Square test. The influence of current joint inflammation on pain sensitivity was determined using a linear regression assessing the correlation of joint diameter with % reduction in mechanical threshold 3 days after the induction of monoarthritis as well as a comparison of joint diameter across 21 days in animals with different pain sensitivities using repeated measures two-way ANOVA with Bonferroni post-hoc analysis.To assess the effect of prior monoarthritis on pain sensitivity, animal groups were compared using two-way ANOVAs with Bonferroni post-hoc analysis. Comparison of weight bearing deficits present prior to the second bout of monoarthritis (at baseline) were made using one-way ANOVA with Bonferroni post-hoc analysis.Pain visual analogue scores (VAS) reported by patients varied considerably at each clinic visit . Despite this variability, pain VAS over the 3 clinic visits could be separated into 8 discrete clusters which were aggregated into 3 larger functionally distinct pain trajectories based on proximity between clusters Fig. : patient2,94 = 193.21, p < 0.001). Disability (CHAQ) and quality of life (PGE) followed similar trajectories .Pain VAS significantly differed between the three trajectory groups across clinic visits (Fp = 0.018) compared to either the low or variable trajectories  or limited joints at that visit (OR(95%CI) = 1.02(0.96–1.09), β = 0.04, p = 0.46). This model examining variables influencing concurrent pain, explained a significant amount of the variance seen in pain VAS scores  but not all (R2 = 0.28).In the patient cohort, pain at any individual clinic visit was significantly associated with physician global assessment (PGA)  = 1.90(1.61–2.23), β = 0.51, 2,94 = 7.64, p = 0.001) in patients with variable (p < 0.05) or high (p < 0.01) pain compared to those with low pain , a pattern similar to that seen when correlating pain and concurrent arthritis activity.Since pain is not associated with measures of current arthritic activity, we investigated the association of factors at study onset with pain trajectory. Average scores for PGA was significantly higher (Fp = 0.035) but they were more likely to have swollen joints (OR(95%CI) = 1.73(1.02–2.95), p = 0.044) or limited joints restricted in movement (OR(95%CI) = 1.57(1.06–2.32), p = 0.026) compared to patients with a low pain trajectory (Table p = 0.033).However, regression analysis assessing the influence of disease activity markers alongside patients characteristics showed that patients with a high pain trajectory were less likely to have active joints at the onset of this study, (OR(95%CI) = 0.62(0.40–0.97), p = 0.096) and more swollen joints (OR (95%CI) = 1.59(0.99–2.57), p = 0.057). This trajectory was not associated with PGA (OR (95%CI) = 1.22(0.90–1.64), p = 0.20).Patients with variable pain were also more likely to have limited joints (OR (95%CI) = 1.531.04–2.26), p = 0.033) than patients with low pain  within patients of each trajectory type revealed that the pattern of joint types differed significantly between the low and variable/high pain trajectories with fewer patients with only active joints but more patients with swollen and limited joint in patients with a variable/high pain trajectory  and reduced weight bearing on the inflamed limb for 21 days  with some variance. Based on mechanical withdrawal thresholds 3–10 days post-injection, animals could be separated into 3 clusters: those with a low (28.0%), medium (36.0%) or high (36.0%) sensitivity to pain. Animals in these three sensitivity groups also exhibited mechanical hypersensitivity after CFA injection for differing timescales , 7 days for animals with medium sensitivity (0 vs. 3–7 days: p < 0.001), and 10 days for animals with high pain sensitivity (0 vs. 3–10 days: p < 0.001).Adolescent rats (P21) with complete Freund’s adjuvant (CFA) induced monoarthritis exhibited clear pain behaviour. This was measured by mechanical hypersensitivity for 7 days post-CFA injection .Weight bearing on the inflamed limb also differed between sensitivity groups  and did not significantly differ between the three sensitivity types over 21 days post-injection  did not correlate with pain behaviour 3 days post-injection . Weight bearing on the inflamed limb  was reduced for 21 days post-injection in Saline+CFA animals  and 24 days post-injection in CFA + CFA animals .To test whether pain trajectory is influenced by previous arthritic activity, pain behaviour was assessed in animals administered low dose joint CFA  twice: once at P8 or P21, and again at P40 Fig. . Overall3.63 = 22.02, p < 0.001; vs. Saline+Saline/Saline+CFA: p < 0.001; Fig. p > 0.050). Sex distribution did not differ the two groups . Reductions in mechanical withdrawal threshold  and joint inflammation did not differ between groups .The effect of a second CFA injection upon pain behaviour, differed significantly between the low and high sensitivity groups. Animals with high sensitivity experienced significantly longer lasting pain, measured as a reduction in weight bearing, after the second CFA injection , nor did other discrete disease-related variables (JIA subtype or medications administered) differ between trajectories. However, a different subjective measure of disease activity–the physicians’ assessment (PGA)–did correlate with pain reported at an individual visit. Evaluating factors related to each pain trajectory we found that, while active arthritis is less likely in patients with high pain, these patients had more swollen and limited joints suggesting that prior arthritic activity may influence the progression of pain.This was explored in the second part of the study using an experimental animal model of joint inflammation to examine the role of prior inflammation in the development of persistent pain. Recurrent joint inflammation was established through the administration of CFA at two time-points. As predicted from the patient data, a prior bout of inflammation exacerbated pain, measured by weight bearing, but only in animals with higher baseline levels of pain sensitivity.Divergent pain trajectories have been shown previously in JIA –10. StudPsychosocial variables  were not included in this analysis due to the retrospective nature of the data collection. Despite this limitation, our data suggests that prior arthritic activity can exacerbate pain in individuals with high sensitivity to inflammatory pain. In patients, increased limited joint count was associated with variable and high pain trajectories, despite a lack of correlation between limited joints and pain reported at a single visit. Limited joint count is not typically included in analyses of factors influencing pain, indicating the novelty of this discovery. However, association does not necessarily indicate cause and it is hard to define the chronology of arthritic activity and pain. Indeed, pain within 6 months of JIA onset has been associated with increased disease severity, notably polyarticular disease and continued pain/disability at 5 or 8 years after JIA onset , 22.Severe JIA has been differentiated into those requiring more medication but achieving control of arthritic activity and pain and those who, despite intensive treatments and comparable arthritic activity, continue to report pain and reduced quality of life . This suWith variations present in the pain trajectories in JIA patients, cross-species studies can facilitate characterisation of the relationship between disease activity and pain and dissect out underlying mechanisms. Our results from rodents suggest that–even within a colony of Sprague Dawley rats from a single institution–there are differences in innate sensitivity to inflammatory pain leading to low or high pain trajectories in arthritis. Here we show that the relationship between high pain and prior arthritic activity is dependent on this sensitivity. Individual pain sensitivities in rodents have been described elsewhere, focussing on genetic differences between rodent strains –27 or beWe have previously proposed that preceding painful events may exacerbate pain in JIA,  and hereThis work shows that both patients with JIA and rodents with experimental joint inflammation have individual sensitivities to arthritic inflammatory pain which is not related to current joint inflammatory status. A significant number of both JIA patients and rodent models have pain that is persistently higher or more prolonged than other individuals of the same age, sex and arthritic activity. The results support the hypothesis that prior, rather than current, arthritic activity may be an explanatory factor for those individuals with a high sensitivity to inflammatory pain.Additional file 1:Table S1. JIA disease activity markers for each pain trajectory. Table S2. Patient characteristics of included and excluded patients. Figure S1. Disability and quality of life as reported by patients with different levels of pain. Figure S2. Ven diagrams examining proportions of patients with each type of joint count. Table S3. Animal numbers and the distribution of pain trajectories in female and male adolescent rats. Table S4. Animal numbers and characteristics of animal groups receiving one or two bouts of monoarthritis. (DOCX 353 kb)


Liposomal bupivacaine demonstrated promise decreasing postoperative pain in total hip and total knee arthroplasty (THA/TKA). Some randomized trials have shown non-superior results; however, confounding variables were not accounted for in such analyses. This study attempts to determine risk factors associated with failure of pain management in patients receiving liposomal bupivacaine.Postoperative pain scores were collected following primary or revision arthroplasties between January 2016 and December 2017. Retrospective analysis of institutional total joint quality and outcomes registry was screened and patients undergoing primary or revision arthroplasties who completed a multi-modal pain management including liposomal bupivacaine were included in the study. Patients with a history of infection/deviated from the institutional pain management protocol were excluded.A total of 237 patients were included for analysis. Younger patients less than 64 years old had significantly higher pain scores between 0 and 12 h and > 24 h. Active smokers had significantly higher pain scores between 0 and 6 h and > 24 h. Patients with a history of opioid use/pain management had significantly higher pain scores at 6-12 h and 24-48 h. Regression analysis indicated risk factors for resistance to liposomal bupivacaine are younger patients less than 64 years old, those undergoing primary THA, and patients with a history of smoking/pain management/opioid use.We identify risk factors for resistance to liposomal bupivacaine, which include younger age less than 64 years old, history of smoking/pain management/opioid use. Future studies should use these risk factors as exclusion criteria when using liposomal bupivacaine or initiating any randomized trials regarding efficacy. Control of postoperative pain in the setting of primary total hip and total knee arthroplasty (THA/TKA) is critical for successful outcomes leading to quicker recovery, reduced readmission rates, and lower treatment costs . CurrentWhile most of the bias was removed with these level 1 trials, these studies, along with its predecessors, do not include subset analyses that may provide more insight into pain control failure . In thisInstitutional Review Board (IRB) approval, study number 20171537, was obtained to collect patient outcome data following THA and TKA at our institution. A single surgeon, consecutive cohort of 286 consecutive patients undergoing either THA or TKA between January 2016 and December 2017 were retrospectively reviewed. Retrospective analysis of institutional total joint quality and outcomes registry was screened for inclusion. Inclusion criteria consisted of any patient undergoing primary or revision arthroplasties with completed multi-modal pain management strategy and received liposomal bupivacaine  and orthopaedic floor nursing protocol, pain scores were assessed and recorded via the Wong-Baker Visual Analog scale (VAS). Timepoints included times at 2, 4, 6, 8, 12, 24, and 48 h post-operatively.p-values where > 25% of cells have expected counts < 5. The main outcome measured was highest pain score (0–10) recorded within a 48 h window post-op. The relationship between patient demographics and surgical variables with highest post-op pain score was assessed with absolute differences (AD) and 95% confidence intervals (95% CI) using bivariate and multivariable linear regression analysis. Variables with a p-value < 0.05 from the bivariate analysis were included in the multivariable model. A p-value of < 0.05 was considered to be statistically significant in all calculations. All statistical analysis was performed using SAS 9.4 .Frequencies and proportions of categorical patient demographic and surgical variables are reported. Means and standard deviations (SD) of continuous patient demographics and pain score variables are reported. To test for differences in demographic and surgical variables based on pain failure at 0–6, 6–12, 12–24, and 24–48 h time intervals, chi-square tests were calculated for categorical variables and one-way ANOVA tests were calculated for continuous variables. Fischer-Exact tests were used in place of chi-square tests to obtain 2, and 155 (68.6%) patients were female. Surgery was performed in the right lower extremity in 133 (58.3%) patients with a primary total knee making up a majority of the procedures (54.7%), followed by primary total hip (29.6%), then revision total knee (8.1%), revision total hip (6.7%) and bilateral knee (0.9%). A majority of patients did not receive PCA (78.7%). Spinal/epidural blocks were administered to 26 (11.3%) patients, femoral/intraarticular blocks to 11 (4.8%) patients, and 193 (83.9%) received no blocks. A total of 47 (21.0%) of patients were current/former smokers, and 42 (18.7%) used alcohol. Patients with a history of pain management made up 41.8% of the population, and 42.5% of patients took pain medication at home . A total of 21 (9.3%) of patients were taking steroids and 23 (10.1%) taking antidepressants at the time of surgery. Diabetics made up 29.7% of the population  patients experienced pain failure at 0–6 h post-op, 65 (35.7%) patients at 6–12 h post-op, 147 (71.4%) patients at 12–24 h post-op, and 171 (79.5%) patients at 24–48 h post-op. Mean highest pain score was 1.8 ± 1.8 in the PACU, 4.3 ± 3.1 at 0–6 h post-op, 4.2 ± 3.1 at 6–12 h post-op, 6.4 ± 2.8 at 12–24 h post-op, and 6.8 ± 2.6 at 24–48 h post-op. Overall, within the first 48 h post-op, mean highest pain score was 7.5 ± 2.2 and a total of 205 (86.5%) of patients experienced pain failure at least once (Table 8.4% patip = 0.002), 6–12 h , and 24–48 h  intervals. Among patients with a history of pain management, a higher proportion of patients had pain failure at 6–12 h  and 24–48 h  intervals. A higher proportion of pain failure was also observed in patients who were on opioid pain medication at home at 6–12 h  and 24–48 h  intervals. Patients who were not on any pain medication at home were less likely to experience pain failure at 6–12 h  and 24–48 h  intervals. A higher proportion of smokers experienced pain failure within the first 0-6 h postop  and patients who received PCA after surgery experienced a higher rate of pain failure 12–24 h after surgery . Gender, BMI, side of surgery, type of surgery, type of block received, alcohol usage, steroid usage, antidepressant usage, and prior diagnosis of diabetes were not significantly associated with pain failure at any time interval 0-48 h after surgery   and primary total hip procedure was associated with a lower pain score by greater than 1 point compared to primary total knee procedure  (Table Multi-modal pain protocols following THA/TKA have become the standard of care –5. Oral Our current study investigated the efficacy of pain control after liposomal bupivacaine injection following TKA/THA at various time intervals in order to ascertain risk factors leading to resistance of liposomal bupivacaine. Results from our study demonstrated that a total of 86% of the 237 patients included had pain failure at least once during the first 48 h. Not surprisingly, smokers, younger patients less than 64 years old, and patients with prior opioid use, experienced significantly higher rates of pain failure at various time intervals (Table This study does have some limitations. Power calculation at 0.80 and alpha of 0.05, yielded a R-squared coefficient of 87.5% indicating significance for the regression analysis performed. At a power of 0.90, however, R-squared coefficient fell to 52.3%, offering a less reliable significance at a higher power. However, with a significant R-squared at a power of 0.80, the authors considered the statistical significance appropriately interpreted for the conclusions found in this study. Another limitation of this study is a lack of control group. When examining our data, we found that our baseline pain scores were in line with historical controls; therefore, a control group was assessed. In addition, retrospective analysis of a registry may have led to potential inherent bias; however, the goal of this study was not to demonstrate superiority but rather identify risk factors for failure of pain management with liposomal bupivacaine. Lastly, there were select patients who were provided with PCA, regional block, or spinal anesthesia, which may influence pain scores for patients receiving liposomal bupivacaine, but this was also taken into consideration in our statistical analysis.Liposomal bupivacaine has been shown to be efficacious in pain control management following primary and revision arthroplasties. However, our study demonstrated that younger age less than 64, and a history of smoking, pain management, and opioid use, led to failed pain management after use of liposomal bupivacaine as part of a multi-modal pain regimen. Future studies should use these criteria as exclusion criteria when using liposomal bupivacaine or initiating any randomized trials regarding efficacy.