Dental Press Journal of Orthodontics to coordinate an interview with Dr. Jeffrey Okeson. I have known Dr. Okeson for over 14 years. All started when I had the fantastic opportunity to be one of his residents for 3 years, and ever since, he has been my mentor and my friend. Dr. Jeffrey Okeson, despite of being a very famous and tremendously talented professional, continues to be an extremely nice and simple person. Due to these and many other reasons, I call him “my American Father”!!! He is married for 48 years to Mrs. Barbara Okeson, and they have two sons and one granddaughter. Dr. Okeson has a twin brother who is also a dentist. He enjoys jogging and has continued to jog for over 40 years. He also enjoys traveling and meeting people. Dr. Okeson has more than 240 professional publications. One of his textbooks, Management of Temporomandibular Disorders and Occlusion, is used in most of the United States dental schools and has been translated into eleven different foreign languages. Dr. Okeson has presented more than 1,200 invited lectures on the subject of TMD and orofacial pain in all 50 U.S. states and in 57 different countries. He has received multiple awards, including the first ever “Distinguished Alumni Award” from the College of Dentistry/University of Kentucky, and “The International Dentist of the Year Award” from the Academy of Dentistry International, which is the highest award recognized by this Academy. He has also been inducted into the University of Kentucky Hall of Distinguished Alumni and received the Governor’s Council on Postsecondary Education’s Acorn Award, given to top college professor in the State of Kentucky. Now is time to enjoy reading the interview! It was with great joy that I accepted the invitation from the Felipe Borges Porto (Interview coordinator)Dental Press Journal of Orthodontics para coordenar uma entrevista com o Dr. Jeffrey Okeson. Conheço o Dr. Okeson há mais de 14 anos. Tudo começou quando tive a fantástica oportunidade de ser um de seus residentes por 3 anos; desde então, ele tem sido meu mentor e meu amigo. Apesar de ser um profissional muito famoso e extremamente talentoso, o Dr. Jeffrey Okeson continua sendo uma pessoa extremamente simpática e simples. Devido a essas e muitas outras razões, eu o chamo de “meu pai americano”!!! Ele é casado há 48 anos com a Sra. Barbara Okeson, e eles têm dois filhos e uma neta. Dr. Okeson tem um irmão gêmeo que também é dentista. Ele adora correr, o que já faz há mais de 40 anos. Ele também gosta de viajar e conhecer pessoas. O Dr. Okeson tem mais de 240 publicações profissionais. Um de seus livros, Management of Temporomandibular Disorders and Occlusion, é utilizado na maioria das faculdades de Odontologia dos Estados Unidos, e foi traduzido para onze idiomas diferentes. Dr. Okeson apresentou mais de 1.200 palestras sobre os temas DTM e Dor Orofacial em todos os 50 estados americanos e 57 países diferentes. Ele recebeu vários prêmios, incluindo o primeiro Distinguished Alumni Award da College of Dentistry/University of Kentucky, e The International Dentist of the Year Award da Academy of Dentistry International, que é o prêmio de mais alto reconhecimento oferecido por essa academia. Ele também foi incluído no University of Kentucky Hall of Distinguished Alumni e recebeu o prêmio Council on Postsecondary Education’s Acorn Award, dado ao melhor professor universitário no estado do Kentucky. Agora, é hora de apreciar a leitura da entrevista! Com grande alegria aceitei o convite do Felipe Borges Porto (coordenador da entrevista)1) In your opinion, can occlusion have any influence on the development or aggravation of temporomandibular disorders (TMD)? (Daniela Feu)The role of the occlusion and TMDs has been debated for many, many years.2) What is the role (if any) of orthodontic treatment in controlling temporomandibular disorders? Are there parameters to be followed by the orthodontist during treatment and in the finalization of patient’s occlusion that may reduce the chances of developing TMD in the future? (Daniela Feu)These are very important questions. When we look at the five etiologic risk factors, orthodontic therapy can only influence one: occlusion. Therefore, from the very beginning, orthodontic therapy has only a minimum effect on TMD. However, it is important that the orthodontist recognizes how occlusion can become a risk factor for TMD. Where and how the teeth occlude has a very important relationship with temporomandibular joint function. Orthodontists should appreciate that they are truly orthopedists and need to understand the orthopedic stability in the masticatory structures. It is my belief that the most stable joint position is when the condyles are in their most superior anterior position in the fossae, resting against the posterior slope of the articular eminences, with the discs property interposed. This is an orthopedically stable joint position as determined by the muscles that load these joints. I believe it is important that in this stable joint position, the patient can achieve a stable occlusal position. The most stable occlusal position is maximum intercuspation. Therefore, orthopedic stability in the masticatory system is achieved by having both joint stability and occlusal stability that coincide. Orthodontic therapy routinely changes the patient’s occlusion. I believe every orthodontist should have as a final treatment goal to produce orthopedic stability in the masticatory structures. This means, establishing a stable joint position  that is in harmony with a stable occlusal position.It is reasonable to assume that orthopedic stability would reduce risk factors for developing TMD. However, producing this orthopedic stability in the masticatory structures by no means guarantees that the patient will not develop TMD. Always remember that there are four other etiologic risk factors associated with the development of TMD. I believe it is important that we do not suggest to the patient that orthodontic therapy will prevent TMD. An orthodontist may establish a stable orthopedic relationship and then other risk factors, such as trauma or emotional stress, could precipitate a TMD.3) The relationship between orthodontic treatment and TMD has been extensively investigated, and despite the fact that most studies indicate the lack of relationship between those, yet no consensus has been achieved. Considering the fact that all studies that investigated such relationship analyzed treatments performed by orthodontists , do you think there is a chance that poor orthodontic treatment could lead to a higher risk of developing TMD? Since there is an increase in treatments involving dental movements performed by dentist without extensive understanding in orthodontics, do you think that new longitudinal studies may start presenting stronger association between orthodontic treatment and TMD? (Felipe Porto)I would certainly agree that most studies investigating the relationship of orthodontic therapy and TMD do not suggest a strong association.Perhaps one of these reasons is related to the discrepancy between a stable joint position and the stable occlusal position. As dentists, we have a very mechanical mind and we desire precision in our dentistry for success. Therefore, even very slight discrepancies between a stable joint position and a stable occlusal position has been described as a malocclusion. In my opinion, most patients have a discrepancy of 1-2 mm. These discrepancies have not been shown to be significantly correlated with TMD symptoms. However, in mostly epidemiological studies, slides that are greater than 3 to 4 mm from a stable joint position to a stable occlusal position become more significantly correlated to symptoms.Another consideration that may have influenced the results of these studies is the fact that most orthodontic therapy is accomplished in young healthy growing adolescents. Often the occlusal condition is finalized before the condyles have fully matured. When this occurs, a stable intercuspal position allows the patient to function while condyles mature into their stable functional position. Therefore, function encourages development of the condyle into its musculoskeletal stable position (form follows function). Significant discrepancies between this position and the stable occlusal position are rarely found.Another consideration is that most, if not all, the studies that have investigated the relationship between orthodontic therapy and TMD symptoms have been accomplished in graduate orthodontic training programs. It seems reasonable to assume that treatments provided in these teaching facilities are highly supervised and at the highest level of orthodontic therapy. Perhaps orthodontic therapy that is less than ideal may pose increased risk factors, potentiating TMD symptoms. There may be some orthodontists who reviews these studies and conclude that orthodontic therapy can never influence TMD symptoms. I believe this is misinterpretation of the data and could place some patients at increased risk. I also have some concerns regarding newer orthodontic therapies that do not focus much attention on either a sound intercuspal position and/or joint position. Only time will tell if these new orthodontic technics are associated with TMD risk factors.4) Most of our readers are clinical orthodontists and occasionally they come across patients complaining of joint sounds that had its onset in the course of treatment. Is it possible that TMJ disc displacements are results of the orthodontic mechanotherapy, and what would you recommend to the orthodontist in these cases? Epidemiological studies suggest that clicking is a common clinical finding in the general population. It seems to begin in the teenage years, increasing into the 20s and 30s. Studies also suggested clicking is not often associated with significant clinical symptoms.5) It is very common to have patients seeking orthodontic treatment because they have associated occlusal problems with TMD (muscular and/or intracapsular). In your opinion, what is the ideal treatment sequence: a) to treat the TMD first and then initiate the orthodontic treatment; b) to treat both conditions simultaneously; c) to perform orthodontic treatment monitoring the progression of the TMD? (Fábio Sato)As previously mentioned, I believe it is very important to assess the function of the masticatory system prior to beginning orthodontic therapy. If signs and symptoms of TMD are present, they should be discussed with the patient (parents). If the symptoms are significant, they should be managed before starting orthodontic therapy. This is important because if orthopedic instability is present, it needs to be identified as a potential risk factor for TMD symptoms. Once the symptoms have been resolved, a stable joint position can be determined so that the orthodontic therapy can provide a sound occlusal position in harmony with this joint position. A stabilization appliance may be helpful during this treatment period. If a stabilization appliance is utilized and the TMD symptoms are not resolved, is likely that the etiologic risk factor(s) is not malocclusion and therefore the orthodontic therapy will not likely affect the TMD symptoms. The patient should be aware of this before orthodontic therapy is begun. Achieving improved esthetics is still a possible treatment goal, but reasonable treatment expectations need to be presented to the patient prior to beginning treatment.6) In patients with an orthopedically unstable occlusion, severely mutilated dentition and pain, how would you approach the TMD prior to the occlusal rehabilitation? (Bruno Furquim)When a patient presents with TMD symptoms and also needs significant dental procedures, the TMD symptoms should be managed first, before any dental procedures are attempted . Once the TMD symptoms have been resolved, a stable jaw position can be better identified to carry out the extensive dental procedures. Also, eliminating the TMD symptoms first may provide the clinician with insights regarding the appropriateness of the needed dental procedures.7) It is common for the population and for many health care professionals (including some dentists) to believe that orofacial pain is the same as TMD. Many of those professionals tend to label facial pain patients as “crazy” when TMD or dental problems are ruled out. Why do you think this happens? Where does TMD fit the full range of orofacial pain? (Felipe Porto)“I do not know”, and the only other alternative is to blame the patient. I have learned that telling a patient it is “all in his/her head” is extremely devastating to human spirit. In my opinion, pain in the oral and facial regions is rarely caused predominantly by psychologic factors. Certainly, pain in the face produces psychological issues such as depression, anxiety, helplessness, hopelessness and frustration. These conditions can most surely enhance the pain experience and sometimes mask other etiologies. I would hope that clinicians gain more insights to the complexity of pain and be more comfortable saying “I do not know the reason for your pain but I will refer you to someone who may have a better understanding of what may help.”This is a very sad, but true, statement. Many clinicians who do not see a dental cause for the pain symptoms will quickly declare that the patient is “crazy”. In my opinion, the best explanation for this is that these individuals do not have a complete understanding of orofacial pain. Temporomandibular disorders are musculoskeletal disorders of the masticatory system. There are many types of TMDs and I have a complete textbook8) Current literature is categorical about the high association between anxiety and temporomandibular disorders. Although association does not imply causation, we are suggested to intervene in anxiety to have better results in chronic pain management. How are these patients treated at your center? Data certainly reveal that anxiety, and other psychosocial issues, are often associated with chronic pain conditions.9) Why do you think that many dentists believe that TMD is always related to a dental problem? And what are the implications of such belief? (Felipe Porto)“if the only tool you have is a hammer, the whole world starts looking like a nail”. We were trained by mentors who we believed and trusted. However, as evidence-based medicine became more predominant in our field, we needed to review traditional belief models. As I mentioned in an earlier question, there is a potential component of occlusion in TMD, but there are many other factors that need to be considered. The clinician who has a strong belief model in occlusion will likely focus on that aspect, and not appreciate the more common etiologies related to TMD. This would not be in the best interest of the patient. There is nothing more disheartening for the patient, as for the clinician, than spending months or years changing the patient’s occlusion only to fail to resolve the pain problem. This is exactly why establishing the proper diagnosis is the most critical thing you can do for your patient. It is only after establishing the proper diagnosis that you can select the correct treatment that will be effective for the patient. In my opinion, extensive dental procedures are not necessary for most patients with TMD. However, if that is all you know, what else can you do? Do not fall into this trap. Educate yourself in this area of study so that your patients will receive the most appropriate and most conservative treatment needed to resolve the problem. It is very hard to break tradition. Early on, our profession assumed that TMJ disorders were predominately related to occlusion mainly because that is what we knew best. This likely relates to the old adage that states 10) In Brazil, there is a massive and injudicious use of botulinum toxin type A in the “treatment/control” of bruxism and temporomandibular disorders in general. In your opinion, what are the indications for this drug in our specialty? I have been using onabotulinum toxin injections in my chronic pain patients for nearly 20 years. I have learned that there are some indications, but often onabotulinum toxin injections can be misdirected and used inappropriately. It seems to have become some type of status symbol or fad, and its use needs to be placed in proper perspective. The condition I believe to be the most indicated is oromandibular dystonias. This is the most effective and appropriate treatment for these patients. However, this condition is relatively rare in a practice setting. I do not feel it is suitable for most patients with bruxism, because there is more appropriate treatment available. Onabotulinum toxin injections can certainly weaken the muscles of mastication, which reduces loading to the teeth.,We are learning that onabotulinum toxin may have a positive effect on pain, far greater than just weakening muscles. Evidence is arising that onabotulinum toxin may have a positive effect on reducing neuropathic pain.11) One of the changes that I currently see in the profile of patients treated with TMD is the increasing number of children and adolescents compared to patients in the past, who were basically adults. What therapeutic approach is used in such pediatric cases, since many treatments used in adults cannot be applied in children? (Fábio Sato)I am not convinced the actual incidence of TMD is increasing in children and young adolescents, even though we may be seeing more of these patients. Perhaps a better explanation is that we, the professionals, have become more sensitized to these conditions and therefore identifying them earlier. I believe young adults experience similar etiologic risk factors related to TMD as do adults.12) According to your studies and experience, is there any relationship between the chronic use of mandibular advancement devices for the treatment of obstructive sleep apnea and the development of TMD? (Daniela Feu)Several years ago, one of our orofacial pain master’s students, Dr. Cristina Perez, investigated whether dental sleep appliances posed a risk factor for developing TMD , as well13) In your opinion, what characterize a good occlusal splint? Can it (or should it) have variations depending on specific situations? (Bruno Furquim)The appliance I would recommend for the most common TMD issues is a stabilization appliance. This is a hard, maxillary appliance that produces orthopedic stability in the masticatory system. This means that when the condyles are in their musculoskeletal position, the teeth occlude evenly and simultaneously, directing force through the long axis of the teeth, with adequate anterior eccentric guidance. I would only use another type of appliance for a patient who has a painful disc displacement with reduction. In that situation, I would consider a mandibular anterior positioning appliance for nighttime use only. This can help the painful retrodiscal tissue to adapt. This appliance only provides a temporary therapeutic position that would assist in adaptation, not a permanent jaw position. It should be worn nightly for 1-2 months and then eliminated once the intracapsular pain has been reduced (tissues have adapted).Note that both these appliances should provide full arch occlusal tooth contacts. This will minimize any dental changes. The goal of these appliances is not to permanently change the patient’s occlusion; they are to help manage TMD symptoms.14) In recent years, I have noticed in Brazil an increase in surgeries involving the temporomandibular joint, especially the so-called minimally invasive ones, such as arthroscopy. In your opinion, what is the role of TMJ surgeries in the treatment of temporomandibular disorders? (Fábio Sato)There was a time in the United States when surgeries became very common for the management of TMD. We learned that routine use of surgery is not indicated or helpful in many TMD patients. The majority of TMD patients are very responsive to conservative care and more aggressive procedures are not indicated. However, there are maybe a few individuals who are relatively nonresponsive to conservative care. In these patients, a minimal surgical procedure, such as arthroscopy, may be considered. In my opinion, these procedures should only be attempted when reasonable conservative care has failed.15) The specialty of Temporomandibular Disorders and Orofacial Pain (TMD/OFP) in Brazil was regulated in 2002 by the Federal Council of Dentistry, but even nowadays, many professionals still do not have a complete understanding of the area of expertise of specialists in this field. Unfortunately, many dental schools in Brazil do not yet have a TMD/OFP discipline in their curriculum, and there are few specialists in the area , regardless the high prevalence of this type of condition among the population. How do you see the future of the specialty for the next few years? (Fábio Sato)I have been in the field of TM disorders and orofacial pain for more than 40 years, and it has been very frustrating to see how slow the profession has been to recognize its importance. TMDs are the second most common pain complaint dentists face (toothache is the first). Dentists are the only healthcare providers that understand and manage TMD. Therefore, it would be appropriate for our profession to take the lead in make sure every dentist is trained in this field. This is especially true because in many cases, simple and reversible therapies are effective and easily provided. However, that is still not the case. Making this issue even more difficult is the fact that TMD is only a small part of Orofacial Pain. In United States, the Commission on Dental Accreditation has approved formal training programs in Orofacial Pain. Our program was one of the first to receive this accreditation. These are two-year, full-time programs, educating dentist in evidence-based pain concepts. It is my hope that these programs will flourish and provide sound evidence-based management for clinicians who are interested in orofacial pain. These individuals will go out into practices and be the referring specialist for the complicated chronic orofacial pain patient. It is still my belief that every dentist should have a basic understanding of TMD so that he or she can effectively manage the common, simple, transient TMD symptoms that are often managed successfully with simple, reversible therapies. However, an option should exist for clinicians who are not interested in managing TMD to send their patients to a qualified orofacial pain clinician. This is especially appropriate for the more complicated orofacial pain patient.16) What has changed in your way of diagnosing and treating patients with orofacial pain in the last 10 years and what do you think will change in the near future? I believe our greatest change has been our focus away from occlusion as the major etiologic factor for TMD. Evidence-based medicine has forced us to place stronger emphasis on other risk factors, especially central mechanisms that result in orofacial pain. Perhaps the future should be directed towards a better understanding of why some patients suffer with pain more than others. A better appreciation of human adaptability would be very useful in understanding these conditions of vulnerability to pain.


Introduction: Minimal research has been conducted on the prescribing patterns of emergency room physicians. The opioid epidemic is a well-known public health crisis and increased knowledge of providers’ tendencies to prescribe opioids over other analgesia may help to update guidelines, improve patient safety, and lower the amount of opioid diversion and death from overdose. The purpose of this study was to determine the association between patient visit demographics and prescribed opiate analgesics.Methods: We conducted a retrospective study analyzing adult patient visits that were seen in the emergency setting for acute pain including chest pain, back pain, abdominal pain, headache, face/tooth/ear, or musculoskeletal pain, utilizing the 2011-2016 National Hospital Ambulatory Medical Care Survey Emergency Department Patient Record dataset. We analyzed the relationship between various patient visit characteristics and whether opiate analgesics were given or prescribed. Results: Our study included 73,983 visits for pain, representing an estimated 407 million weighted visits over the study period. We found that those who received opiates were more likely to be female, 62.9% vs. 60.2% and more likely to be white, 74.2% vs. 71.3 %. Furthermore, visits that received opiates were more likely to be younger, have private insurance, and be in increased pain . Conclusion: We found that certain patient visit characteristics - including being female, white, younger, and private insurance - were given opiates more in the emergency department. Females have been found to report more pain, the elderly have special considerations regarding pain medications (including the risk of delirium and drug-drug interactions), while insurance status may be confounded by age (Medicare being a large portion of government insurance). However, explanations for differences in prescription rates by race could not be easily discerned. The opioid epidemic is a well-known public health crisis. Economically, the nonmedical use of prescription opioids in 2007 was estimated at $55.7-$25.6 billion due to workplace costs, $25 billion due to healthcare costs, and $5.1 billion due to criminal justice costs . EDs areWe conducted a retrospective study analyzing adult patients, 18 years or older, that were seen in the emergency setting with a reason for the visit of acute pain using the 2011-2016 National Hospital Ambulatory Medical Care Survey (NHAMCS) Emergency Department patient record dataset. The NHAMCS-ED is an annual multistage probability sample of visits made to United States emergency departments, conducted by the Center of Disease Control National Center for Health Statistics. Acute pain included chest pain, back pain, abdominal pain, headache, or other pain. We excluded patient visits who presented with poisoning, injury, or overt trauma as well as pregnant patients. The Multum Lexicon Plus system was used to classify drugs and identify opioids which included codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, oxycodone, tramadol, and any of these drugs used as a single agent or in combination with other medications. We evaluated whether patients were given or prescribed opioids, single and combinations, or nonsteroidal anti-inflammatory drug (NSAID)/acetaminophen analgesia during their visit. Independent variables used during this study included gender, race, age, pain scale, insurance status, whether the patient was seen in the emergency department within the last 72 hours prior to present visit, whether the visit took place in a Metropolitan-Statistical-Area (MSA) or non-MSA, and geographical census region that the visit took place in .The data was analyzed using Statistical Package for Social Sciences (SPSS) Complex Samples 25.0 in a manner that accounted for the NHAMCS complex sample survey design. We analyzed the data using summary statistics and bivariate comparisons such as Chi-square tests. All significant tests were two-sided, and we used a p-value of less than .05 for significance. Institutional Review Board approval was obtained through the University of North Dakota.Our study included 73,983 visits for pain, representing an estimated 407 million weighted visits over the study period. During which, 61% of visits were female patients while patients had a mean age of 45.9±0.2 years. Opiates were given at approximately 30.2% of visits. We found that those who received opiates were significantly more likely to be female (P = 0.000), 62.9% to 60.2% [Table We found that certain patient visit characteristics, including being white, female, and younger, were more likely to be given or prescribed opiates in the emergency department. Visits that were given or prescribed opiates were more likely to be white and less likely to be black or other races. Pletcher et al. reported similar significant differences in opioid prescribing by race/ethnicity in US emergency departments, finding that white patients were more likely to receive opioids than black patients. It was further reported that this prescribing differential became more evident as patient-reported pain severity increased, with adjustment for severity not substantially affecting the differences. The differential persisted throughout all types of pain visits . MoreoveAccording to the American Geriatrics Society Beers Criteria, which describes potentially unsuitable prescription medications for the elderly, only meperidine was included in our protocol. No other opiate was listed as inappropriate for older adults. However, physicians prescribing opioid medications to the elderly have special considerations that do not have to be thought of when giving opioids to younger populations. Older adults are at an increased risk of developing delirium, increased risk of a drug-drug interaction, and increased risk of a drug-disease interaction when taking opioid pain relievers . AdditioSeveral additional reasons that influenced patients receiving opioids during their ED visit have been previously addressed. Some physicians have admitted to giving opioid analgesic to patients with the intent of improving patient satisfaction results . Others Strengths of our study included a national dataset with a large sample size. However, having a large sample size may result in small differences being found as statistically significant without necessarily being clinically relevant. Limitations included pain being self-reported by the patient, making this variable subjective.We found that those who received opiates in the ED were more likely to be female, white, younger, and have private insurance. Differences in opioid prescription rates due to patient gender, age, or insurance status may be due to logical reasons as females have been found to report more pain, the elderly have special considerations regarding pain medications (including risk of delirium and drug-drug interactions), while insurance status may be confounded by age (Medicare being a large portion of government insurance). However, explanations for differences in prescription rates by race, could not be easily discerned. Future research in this area will help elucidate and more clearly quantify the presence of bias in opiate prescription patterns regarding non-modifiable patient characteristics.


To determine the effectiveness of Transcutaneous Electrical Nerve Stimulation (TENS) in management of neuropathic pain in post-traumatic incomplete spinal cord injury patients.A quasi-experimental study was conducted at from January 2017 to June 2017 at Paraplegic Center Hayatabad, Peshawar. Total 60 incomplete spinal cord injured patients with diagnosis of neuropathic pain were subjected to high frequency TENS of 80 HZ. One session was of 45 minutes while there were two sessions per day. TENS was applied for four days in a week and all patients were followed for eight week duration. Pain intensity was measured by using VAS .Mean pain intensity on VAS at baseline was 6.45 which was decreased to 4.77 post intervention at day-1 while it was decreased to 3.48 at day-4 of week one. After application of TENS for 8 weeks, mean pain intensity was decreased to 2.80 ± 1.74. During the consecutive sessions of the TENS application, the pain intensity decreases in a linear fashion and there were significant difference (p<0.05) between pre and post treatment sessions.TENS is useful and safe adjuvant in spinal cord injury patients for the management of neuropathic pain. Spinal Cord Injury (SCI) is a devastating disability known to human kind.8Pain is a common complication after SCI with prevalence of 18 to 96%, and almost 30% of these pain are diagnosed as neuropathic pain.This quasi experimental study was conducted from January 2017 to June 2017 at Paraplegic Center Hayatabad, Peshawar. Paraplegic center Peshawar is second to none in the country providing comprehensive rehabilitative services to patients with spinal cord injuries.A total of 60 patients with incomplete spinal cord injuries with diagnosis of neuropathic pain and age 20-60 years were recruited in the study using consecutive sampling technique. Complete spinal cord injury patients and/or those with complications e.g. pressure sores, fractures etc. were excluded.TENS with high frequency of 80 HZ was applied to patients of SCI. Time for one session was 45 mints, while there were 2 sessions per day i.e. morning and evening session. TENS was applied for four consecutive days i.e. Monday, Tuesday, Wednesday, and Thursday. Each and every patient who entered into the study was followed for 8 weeks. Pain intensity was measured by using VAS before and after the application of TENS. Comparison between pre and post interventional scores was completed to see whether improvement occurred or not. Ethical approval was obtained from institutional ethical review committee of Paraplegic center, Peshawar.A total of 60 subjects with mean age 52.64±0.48 (ranged from 20-60 years) participated in the study, out of whom 75% (n=45) were male and 25% (n=15%) were female. Majority of the participants  were married while the rest of participants  were single. All the patients were from Khyber Pakhtunkhwa and were Pashto speaking. Most of the participants were laborer , 13 (21.7%) participants were House wives while rest of the participants  were having other professions. Forty six (76.7%) participants had thoracic paraplegia, 11 (18.3%) patients had lumbar paraplegia while 3 (5.0%) patients had cervical tetraplegia.Mean pain intensity on VAS at baseline was 6.45±1.09 which were decreased to 4.77±1.52 post intervention at day-1 of week 1. The mean decreased in the pain intensity was seen through the array of intervention. The mean pain intensity was decreased to 3.48±1.91 at day-4 of week-1. During the consecutive sessions of TENS application, the pain intensity decreases in a linear fashion and there were significant difference (p<0.05) between pre and post treatment sessions. After application of TENS for 8 weeks, mean pain intensity at day 1 of week 8 was 2.99 ± 1.33 which was decreased to 2.92±1.2 on day-two and 2.91±1.5 on day three while 2.80±1.7 on day-4. There was significance difference (p<0.05) in pain intensity at pre and post intervention of each session. SCI is associated with various degree of sensory and motor dysfunctions.Using the Quasi experimental design this study was aimed to determine the effectiveness of TENS in management of neuropathic pain in patients with post traumatic incomplete SCI patients. Result indicated that mean decreased in the pain intensity was seen through the array of intervention. During the consecutive sessions of the physical therapy the pain intensity decreased in a linear fashion and there are significant difference (p<0.05) between pre and post treatment session. Following TENS in patients with post Traumatic incomplete spinal cord injuries, mean pain score at week week-8 and day-4 was decreased to 2.80 which reveals a marked decreased in pain intensity. These results are consistent with a randomized control study which reveals that there was a marked decreased in the pain intensity after each consecutive intervention (application of TENS).20Certain adverse affects of TENS has been reported in literature.23Despite the fact that current study is first of its kind conducted in Pakistan which reported effectiveness of TENS in managing neuropathic pain in spinal cord injury patients, however it has some limitations. First of all, its design was quasi-experimental so the results of current study can be affected by confounding variable. Secondly sample size of current study was small due to which generalizability of the results of current study is questionable.TENS is useful and safe adjuvant in spinal cord injury patients for the management of neuropathic pain. A consistence and long term rehabilitation with TENS in patients with post Traumatic incomplete SCI is useful.AZ: Concept and study design, literature search and literature review, Acquisition of data.AA: Acquisition of data, drafting the manuscript.SB: Analysis & interpretation of data.SM: Critical revision, final approval of the version to be published.


Earlier studies documenting the effect of candidate genes on recovery have seldom taken into consideration the impact of emotional distress. Thus, we aimed to assess the modifying effect of emotional distress on genetic variability as a predictor for pain recovery in lumbar radicular (LRP) and low back pain (LBP).The study population comprised 201 patients and mean age was 41.7 years. The significant association between MMP9 rs17576  and pain recovery remained statistically significant after adjusting for pain intensity at baseline, age, gender, smoking, body mass index, pain localization and emotional distress . In contrast, the association between OPRM1  and pain recovery was abolished in the multivariate analysis . Hence, MMP9 rs17576 and emotional distress independently seem to predict persistent back pain. The predictive effect of OPRM1 rs179971 with regard to the same outcome is probably dependent on other factors including emotional processing.Trial registration The Regional Committee for Medical Research and Ethics reference number 2014/1754 Persistent low back pain (LBP) has a point prevalence of 30% and creates a substantial personal and financial public burden globally –6. LumbaEarlier data suggest that the heritability of back pain range from 30 to 45% . GeneticO-methyltransferase (COMT) affects cortical pain processing and the risk of long-lasting pain conditions [Some of the same genetic polymorphisms may also be associated with supra-spinal neuronal activity including stress-induced depression . Moreovenditions –37. In anditions –40. Finanditions . The OPRnditions  and subjnditions .Taken together, these observations and similar data from other studies suggest that genetic factors linked to pain recovery, may be associated with peripheral inflammation—but also neuronal activity in brain regions associated with emotions. In addition, recent data from our group have documented a robust association between the MMP9 rs17576 as well as OPRM1 rs1799971 variants and pain recovery . Hence, The dataset comprises two ongoing prospective cohorts, which are merged after inclusion but before 5-year follow-up. The methods are previous thoroughly described in our publication in PAIN; “Genetic predictors of recovery in low back and lumbar radicular pain” . This stThe study was conducted in accordance with the Helsinki Declaration. The Regional Committee for Medical Research Ethics (reference number 2014/1754) and the Norwegian Social Science Data Service approved the study protocol and all participants gave their written informed consent at baseline and at 5-year follow-up.Emotional distress was assessed using a short version of Hopkins Symptoms Check List (HSCL-10), 4-point scale, where 1 = no complains, 2 = some complaints, 3 = moderate complaints and 4 = many complaints. The scores summarize and divide on the number of answered questions, with a mean score > 1.85 being compatible with emotional distress symptoms present .Pain intensity was recorded using the visual analogue scale (VAS) with anchor values from 0 (no pain) to 10 (worst possible pain) at rest during the last week at baseline and at 5-year follow-up. A cut off ≥ 3.5 is defined as moderate pain .In patients with LRP, genomic DNA was collected at baseline and extracted from whole blood cells using a FlexiGene DNA isolation kit (Qiagen), whereas in patients with LBP genomic DNA was collected at 5-year follow up and extracted from saliva using an Oragene DNA sample collection kit  according to the manufacturer’s instructions. SNP genotyping was carried out using predesigned TaqMan SNP genotyping assays (Applied Biosystems). Genotypes were determined using the SDS 2.2 software (Applied Biosystems). Phase v.2.1.1 was used to define the COMT haplotypes. Approximately 10% of the samples were re-genotyped and the concordance rate was 100%.Descriptive statistics, t-test and Chi-square test were applied to describe the patients at baseline and 5-year follow-up and evaluate differences between LBP and LRP. Univariate linear regression analysis was performed to estimate the correlation between the eight genetic variants  and pain (VAS) at 5-year follow-up. Further on, we adjusted for emotional distress (HSCL-10) at baseline in the analysis to evaluate the impact of the psychosocial factor. Univariate linear regression analysis also performed to estimate the correlation between emotional distress and pain (VAS) at 5-year follow-up. Significant genetic variants p level < 0.05 were included in multivariable linear regression models where we adjusted for pain intensity at baseline, age, gender, smoking status (yes or no), body mass index, pain localization (LRP or LBP) and emotional distress. All models were checked for collinearity . All statistical analyses were performed using the SPSS (version 22) statistical package. A p-value < 0.05 was defined as being statistically significant.The study population comprised 201 patients, including 92 (46%) females and 109 males (54%) with ages of 18 to 59 (mean 41.7 ± 9.6). An active smoking habit was reported in 34% of the patients. At baseline, patients in both cohorts reported moderate pain intensity (mean VAS > 3.5) with significantly higher pain in LBP compared to LRP (p = 0.012). Regarding emotional distress, the LBP patients reported significantly more complaints (mean HSCL-10 > 1.85) than the LRP patients (mean HSCL-10 < 1.85) (p = 0.001). At 5-year follow up, the LBP patients reported significantly more pain (mean VAS > 3.5) than the LRP patients (mean VAS < 3.5) (p < 0.001). Improvement of emotional distress occurred in both the LBP (mean HSCL-10 < 1.85) and the LRP groups (mean HSCl-10 < 1.85), but a significant difference in emotional distress was seen (p = 0.035). Detailed characteristics of the study population are shown in Table 2 = 0.094). Regarding the genetic variants, the univariate linear regression analysis showed that the associations between MMP9 rs17576 as well as OPRM1 rs1799971 and pain at 5 years remained statistically significant also in this subsample of patients . In the multivariable analysis adjusting for potential confounding effects of baseline pain, pain location (LRP or LBP), age, gender, smoking (yes or no), BMI and emotional distress, only MMP9 rs17576, not OPRM1 rs1799971, remained significant (p = 0.008)  is a valid instrument , it does


The US-based categorization significantly differentiated between NPP and DPD (p < 0.0001), and receiver operating characteristic curve analysis revealed that US categorization based on ≥2 abnormal US features showed the best diagnostic performance for detecting DPD. Thus, US can aid in differentiating DPD from NPP.In this study, we compared ultrasound (US) features between normal parotid parenchyma (NPP) and incidental diffuse parotid disease (DPD). From January 2008 to December 2017, 180 patients underwent neck US before parotid surgery at our hospital. From these, 82 were excluded because of the lack of histopathological data concerning the parotid parenchyma or inadequate US images. A single radiologist blinded to the clinicoserological data and histopathological results, retrospectively investigated all US features and categorizations for the parotid glands using a picture archiving and communication system. Retrospective histopathological analysis of the parotid parenchyma was performed by a single pathologist. On the basis of the histopathological analyses, the 98 patients were divided into NPP (n = 70) and DPD (n = 28) groups. Among US features, parenchymal echogenicity and echotexture showed statistically significant differences between the two groups ( The major salivary glands, including the parotid, submandibular, and sublingual glands, play an important role in preservation of the oral cavity and dental health . The parPrimary Sjögren’s syndrome is a chronic progressive autoimmune disease of unknown etiology . SjögrenThis retrospective study was approved by the Busan Paik Hospital institutional review board (IRB 18–0103), and informed patient consent was waived because of the retrospective study design. From January 2008 to December 2017, 180 patients  underwent neck US including the major salivary glands before parotid surgery at our hospital. Parotid surgery was required for the treatment of known parotid tumors (n = 137) or abscesses (n = 7) or the diagnosis of parotid lesions (n = 36). From the total, 54 patients with insufficient US images or poor-quality US images were excluded, in addition to 28 patients without available histopathological specimens of the parotid gland parenchyma. Eventually, 98 patients  were included in the study.For all study patients, preoperative US was performed by two radiologists with 6 and 16 years of experience in performing neck US, respectively. In our hospital, neck US includes the major salivary glands. The procedure was performed with a high-resolution ultrasound scanner  equipped with a 5–12-MHz or an 8–15-MHz linear probe. US modalities were randomly chosen for each patient. During color Doppler US, a low pulse repetition frequency (700 Hz), low velocity scale (4.0 or 5.0 cm/s), and gain setting (between 75 and 78) were used.A single radiologist (with 16 years of experience in performing neck US after board certification) retrospectively investigated the US findings of the parotid glands in all patients. This investigator was blinded to the histopathological results and clinicoserological data concerning the parotid gland. The following US features were categorized using a picture archiving and communication system: parenchymal echogenicity  and echotexture , gland size , gland margin (smooth or lobulated), and parenchymal vascularity . The adjacent fat and muscle were used as references for determining parenchymal echogenicity. However, the radiologist subjectively decided the size of the parotid gland without concrete criterion. The enrolled patients were subsequently classified into one of four categories according to the number of observed US features: category 1, no abnormal US features; category 2, one abnormal US feature; category 3, two abnormal US features; and category 4, ≥3 abnormal US features.Histopathological findings for the parotid gland were retrospectively analyzed by a single pathologist with 18 years of experience in the histopathological analysis of parotid disease after board certification. This investigator was blinded to the US results and serology and assessed residual parotid parenchyma surrounding the mass on the histology slide. Autoimmune parotitis was defined as the progressive loss of glandular cells, with replacement by lymphocytes and formation of germinal centers associated with fibrosis. When there was evidence of inflammation with features that were not compatible with autoimmune parotitis, a diagnosis of nonspecific parotitis was assigned. Diffuse hyperplasia was defined by diffuse hypertrophy and hyperplasia of glandular cells, with retention of the lobular architecture and no definite nodule formation. The parotid gland was considered normal (NPP) when there was no visual evidence of coexisting DPD. When more than 50% lobules were replaced by fat cells, the diagnosis was diffuse fatty change of the parotid gland.2 test for small cell values, and Fisher’s exact test for categorical variables. Continuous variables are expressed as means ± standard deviation. Associations between individual US features and DPD were evaluated for the determination of significant independent predictors of DPD. The Mantel–Haenszel chi-squared test was also used to evaluate the linear association between individual US features and the incidence of DPD. The diagnostic accuracy of the significant US features and US-based categorization for DPD detection were evaluated using receiver operating characteristic (ROC) curve analysis; the area under the ROC curve (AUC) was compared using the method of DeLong et al. [The acquired data were tested for normality of distribution using the Shapiro–Wilk test. In comparisons of US features and categories between the DPD and NPP groups, we used independent t-tests for continuous variables, Pearson’s χg et al. . The cutp-values of <0.05 were considered statistically significant.All statistical analyses were performed with statistical software . A two-sided The parotid surgery performed for the 98 patients included excision biopsy (n = 16), unilateral parotidectomy (n = 80), and bilateral parotidectomy (n = 2). The locations of the resected parotid glands were right (n = 51), left (n = 45), and both (n = 2). The postoperative histopathological diagnoses included benign mixed tumor (n = 51), Warthin’s tumor (n = 30), abscess (n = 4), basal cell adenoma (n = 2), myoepithelioma (n = 1), tuberculous lymphadenopathy (n = 1), lipoma (n = 1), oncocytic adenoma (n = 1), mucoepidermoid carcinoma (n = 4), basal cell adenocarcinoma (n = 1), lymphoma (n = 1), and metastasis from squamous cell carcinoma (n = 1). On the basis of the retrospective histopathological analysis of the parotid gland parenchyma, 70 and 28 patients were included in the NPP and DPD groups, respectively. Six (21.4%) patients in the DPD group were histopathologically diagnosed with autoimmune parotitis; the remaining 22 were diagnosed with nonspecific parotitis. Among the 22 patients with nonspecific parotitis, three exhibited concomitant abscesses and one exhibited tuberculous lymphadenopathy on the ipsilateral side. Diffuse hyperplasia cases were not observed in any patients.p < 0.0001), whereas gland size, gland margin, and parenchymal vascularity showed no significant differences (p > 0.05). US-based categorization exhibited a statistically significant difference between the two groups (p < 0.0001).The US features for the NPP  and DPD p = 0.749) and echotexture (p = 0.917), gland size (p = 1.000), gland margin (p = 0.659), parenchymal vascularity (p = 0.133), and the US-based category (p = 0.933).Histopathology revealed diffuse fatty change in 13 (13.3%) patients, only three (23.1%) of whom exhibited DPD. There was no significant relationship between diffuse fatty change and the parenchymal echogenicity (p = 0.0035)  showed the highest diagnostic performance in terms of DPD detection ( 0.0035) . The diaThe existing literature demonstrates that US is helpful for the detection of asymptomatic or subclinical diffuse thyroid disease –13, withAccordingly, we investigated five US features and found that only the parenchymal echogenicity and echotexture were helpful for the detection of DPD at a statistically significant level. This result differs from those of previous thyroid US studies, which found significance for all analyzed US features –13. The With regard to the US-based categories, we found that category 3  exhibited the highest diagnostic accuracy in terms of DPD detection. This indicates that the diagnostic accuracy increases with an increase in the number of abnormal US features, similar to the findings in previous thyroid US studies –13. HoweWe also investigated diffuse fatty change in the present study and found that none of the cases exhibited increased parenchymal echogenicity. Furthermore, diffuse fatty change exhibited no significant relationship with individual US features or the US-based category. This could be attributed to the low prevalence of diffuse fatty change (13.3%). Further studies are necessary to clarify this aspect.This study has several limitations. First, all study patients underwent parotid surgery, which may have resulted in selection bias. Second, the image analysis was retrospective for all patients. Accordingly, a limited number of US images were used for analysis. Third, there was no specific criterion for measurement of the gland size, which was determined by the subjective judgement of the radiologist. Fourth, a single radiologist analyzed all US images. Fifth, the histopathological analysis was retrospective, performed by a single pathologist, and based on limited specimens. Most cases exhibited limited parotid parenchyma on the histology slides, which were prepared to focus on the parotid mass. In addition, many cases of excision biopsy  were included. Finally, a specific diagnosis of the type of DPD could not be established because of the lack of serological data.In conclusion, our findings suggest that US can aid in the detection of asymptomatic or subclinical DPD and its differentiation from NPP, with the diagnostic accuracy being the highest when a cut-off of ≥2 abnormal US features is used.S1 Table(XLS)Click here for additional data file.


Background: Hypoalgesic inflammatory bowel disease (IBD), a condition in which patients with active disease do not perceive and/or report abdominal pain, is associated with serious complications and there is a lack of cost-effective, reliable diagnostic methods to identify “at-risk” patients. The voltage-gated sodium channels (VGSC's), Nav1.7, Nav1.8, and Nav1.9, are preferentially expressed on nociceptive neurons, and have been implicated in visceral inflammatory pain. At least 29 VGSC single nucleotide polymorphisms (SNPs) have been implicated in chronic somatic pain syndromes, but little is known about their role in human visceral sensation. We hypothesized that disruptive VGSC polymorphisms result in anti-nociceptive behavior in IBD.Methods and Findings: We performed targeted exome sequencing and/or TaqMan genotyping to evaluate the Nav1.7, Nav1.8, and Nav1.9 genes  in 121 IBD patients  and 86 healthy controls. Allelic and genotypic frequencies of polymorphisms were compared among study groups who had undergone characterization of intestinal inflammatory status and abdominal pain experience. Forty-nine total exonic SNPs were identified. The allelic frequency of only one non-synonymous SNP (rs6795970 [SCN10A]) approached significance in hypoalgesic IBD patients when compared to other IBD patients . Hypoalgesic IBD patients were more likely to be homozygous for this polymorphism .Conclusions: This is the first human study to demonstrate a link between a genetic variant of SCN10A and abdominal pain perception in IBD. These findings provide key insights into visceral nociceptive physiology and new diagnostic and therapeutic targets to consider in IBD and other gastrointestinal conditions associated with chronic abdominal pain. Further studies are required to elucidate the precise pathophysiological impact of the rs6795970 polymorphism on human gastrointestinal nociception. Inflammatory Bowel Disease (IBD) encompasses a group of disorders, including Crohn's disease (CD) and ulcerative colitis (UC), characterized by chronic relapsing inflammation of the gastrointestinal (GI) tract. IBD affects as many as 3 million Americans, most of whom are diagnosed before age 35 . These dIn some instances, however, the lack of abdominal pain in IBD can also pose different but significant challenges. Individuals with so-called hypoalgesic and/or “silent” IBD have grossly evident intestinal inflammatory changes that do not produce significantly painful or other noxious sensations. It has been increasingly recognized that symptom-based assessment tools can be relatively insensitive for accurately assessing IBD activity . Variousv1.7, Nav1.8, and Nav1.9) have recently been implicated as primary mediators of visceral nociceptive function, including that associated with the gastrointestinal tract. Investigations incorporating retrograde labeling techniques have demonstrated the presence of these channels in nociceptive neurons innervating the stomach, small intestine, and colon  in IBD patients would result in anti-nociceptive function and diminished abdominal pain perception.Voltage-gated sodium channels (VGSC's) appear to play an important role in visceral pain perception . In partnd colon . The elefunction –14. In sfunction  or geneton ] and who had undergone a colonoscopy between October 1, 2015 and January 31, 2017.We included patients with established diagnoses of IBD who had (1) undergone a colonoscopy, (2) completed a pain questionnaire (see below) at the time of endoscopy, and (3) had provided a blood sample as part of their participation in the registry and biorepository. In addition, IBD study participants had to meet the following criteria: (1) age ≥ 18 years; (2) established diagnosis of IBD ; (3) no coexisting condition that could explain abdominal pain, including pregnancy, trauma, malignancy, infection, or non-IBD associated inflammatory disorder. We also included a cohort of healthy adult (age ≥ 18 years) control patients who had no documented history of chronic gastrointestinal illness or known pain disorder.IBD patients were excluded if they had an indeterminate form of IBD, microscopic colitis, inflammatory enteritis or colitis not associated with IBD or had not provided information about pain at or within 1 month of the colonoscopy. Patients were also excluded if they had undergone a total colectomy or proctocolectomy at any time or any intra-abdominal surgery within the calendar year prior to the time of the study encounter. Healthy controls were excluded if they had a history of chronic gastrointestinal disease or acute or chronic abdominal pain or other pain disorder.Disease severity and location were recorded for each IBD study participant utilizing contemporary endoscopic, histologic, and radiologic information. CD and UC location and phenotype were classified according to the Montreal Classification system . The sevr = −0.7, p < 0.001), we operationally defined presence of clinically meaningful abdominal pain as SIBDQ pain ratings of ≤ 5 (with 5 defined as “a little of the time”).Abdominal pain ratings were based primarily on responses to the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), that asks patients to grade pain on a frequency-based inverse Likert scale (“How often over the past 2 weeks have you been troubled by pain in the abdomen?”), with 1 representing pain “all of the time” and 7 representing pain “none of the time” . We alsoThere were three cohorts evaluated during this study: 1) IBD patients with active disease who had an SIBDQ pain score of >5   or “hypoalgesic IBD”), (2) all other IBD patients, and (3) healthy control patients. Basic demographic and disease characteristics of each group can be found in Table  IBD patiHigh-quality genomic DNA was isolated from whole blood using silica-based spin columns . Spectrophotometry was used to quantify DNA and the quality of the isolated material was evaluated with an Agilent Bioanalyzer.SCN9A, SCN10A, and SCN11A. This set was specifically designed to capture all exons, the proximal promoter sequence, as well as limited intron sequences and untranslated regions near exons. The target-captured sequencing libraries were constructed using the KAPA LTP Library Preparation Kit  combined with a SureSelectXT Reagent Kit (Agilent Technologies), and sequenced on an Illumina Hiseq 2500 sequencer  at read length of paired-end 2 × 100 bp. Targeted exome sequencing was performed on an initial cohort of 46 IBD patients that included a mixture of individuals with and without inflammation and abdominal pain. Generated reads were aligned with the GRCh37 human reference genome using the Burrows-Wheeler alignment (The custom capture oligo set was designed by the SureDesign platform from Agilent Technologies (SureSelectXT Custom Capture Oligo) against lignment . Variantlignment  was usedp value of 0.1 or less and included the polymorphisms rs4073113 (p = 0.009), rs4234134 (p = 0.057), and rs6795970 (p = 0.096). Twenty nanograms of genomic DNA were amplified per the manufacturer's directions and scaled to a total volume of 5 μL in an Applied Biosystems® Veriti® 384-well thermal cycler for each of the above assay IDs.For rigor and reproducibility, genotype analysis of all 46 IBD samples described above, along with samples from an additional 75 IBD patients  and 86 healthy control patients, was performed with commercially available TaqMan assays using the OpenArray platform on a QuantStudio 12K Flex instrument . This analysis was performed on the single nucleotide polymorphisms (SNPs) identified in the original cohort of 46 IBD patients that achieved a t-test or one-way ANOVA was used to compare continuous variables between groups as appropriate. Fisher's exact test was used to analyze the tables of genotypic and allelic frequencies. Only one polymorphism identified from the targeted exome sequencing performed on the original 46-person IBD cohort approached a significantly higher incidence in the hypoalgesic IBD cohort (rs6795970). This variant was also the only exonic polymorphism that encoded a non-synonymous amino acid change and this SNP has previously been associated with hyposensitivity to somatosensory pain stimulation (http://www.R-project.org). All p values of < 0.05 were considered statistically significant.Patients' baseline and clinical characteristics were summarized as descriptive statistics. Chi-squared or Fisher's exact test was used to compare categorical variables between groups, while independent mulation . As a reAll of the work described herein was performed following the guidelines set forth by and with the permission of the Penn State College of Medicine Institutional Review Board. All study participants gave written informed consent in accordance with the Declaration of Helsinki.p < 0.0001). Each cohort had similar gender distributions. The IBD cohorts were each composed primarily of CD patients, in statistically similar proportions. There were no significant differences in disease location  demonstrated differential expression in “hypoalgesic IBD” patients when compared to all other IBD patients exhibiting a p value of 0.1 or less (Fisher's exact test).Table SCN10A; A1073V). This functional polymorphism was therefore examined in all 121 IBD patients. Homozygotic frequency for the rs6795970 polymorphism was significantly higher in the hypoalgesic IBD cohort when compared to the other IBD patients (p = 0.01)  Table . This waSCN10A; A1073V). As indicated above, this SNP demonstrated an increased homozygotic frequency in the “hypoalgesic IBD” cohort compared to other IBD patients. This finding is significant for a number of reasons. Although other studies have provided evidence for links between specific SNPs and syndromes associated with visceral hypersensitivity . This polymorphism encodes a non-synonymous amino acid substitution . This is an important finding that provides key insights regarding visceral nociceptive physiology and new potential diagnostic and therapeutic targets to consider in patients with disorders of abdominal pain perception.There is growing evidence that this particular polymorphism (rs6795970) and the associated Naf NaV1.8 , 25, 26.f NaV1.8 . Functiof NaV1.8 . This isWe are confident in the results of this investigation for several reasons. Our study determined current IBD disease activity through direct endoscopic evaluation of the intestinal mucosa and coupled this information with contemporary validated survey results relating to patient abdominal pain experience. We performed a comprehensive evaluation and analysis of the three VGSC genes of interest  and compared all of the resultant SNPs  among the study cohorts. The initial genetic findings were “double-checked” by Taqman PCR and additional samples were evaluated using the same methodology. These results make us feel more assured of the findings and the significant influence that the rs6795970 SNP has in this context, particularly because it was the only variant encoding a non-synonymous amino acid change that was found to be significantly different in prevalence among any of the study cohorts.Potential limitations of this study include the relatively small sample size and the fact that it was performed using individuals from a single medical center. It will be important to independently validate the results of this investigation with larger numbers of the same patient cohorts. It would also be informative to perform this analysis in other conditions associated with chronic abdominal pain, including irritable bowel syndrome. Our determination of hypoalgesic IBD was also based upon the survey responses and colonoscopic findings from one clinical encounter. It would be useful to determine how consistent these findings (and the study cohorts) were between different time points. Additionally, our cohort of interest focused only on abdominal pain experience and did not include consideration of other symptoms frequently associated with IBD, such as diarrhea, bleeding, and bloating. We utilized this approach in order to minimize potential confounding that could occur in the process of interpreting our data. However, future analyses incorporating individuals lacking the additional symptoms described above could provide a more complete understanding of the so-called “silent” IBD phenotype, which has been associated with lack of perception and/or reporting of any symptom that could be associated with this disorder. The mean allelic frequency of the rs6795970 SNP in our total cohort was ~59%, which is significantly higher than that previously reported  sugV1.8 is important to visceral nociceptive function, particularly in the setting of IBD. In addition to confirming this concept in a larger population of IBD patients, it will also be important to evaluate healthy control cohorts in addition to other gastrointestinal conditions associated with alterations in visceral sensation  to determine whether the impact of this channel and the genetic variant described above is limited to inflammatory conditions of the gut. It will also be important to further evaluate the relationship between the rs6795970 polymorphism, and NaV1.8 function in general, and visceral pain perception through mechanistic studies incorporating targeted genetic changes and objective measures of pain response .Despite these drawbacks, we believe the results of this study provide compelling evidence that NaV1.8 and pain perception in IBD , this will represent a novel, new target to help identify patients at higher risk of major disease-associated complications. It could also serve as a new model to help develop less toxic pain therapies in patients with chronic abdominal pain. This could help to minimize the use of other frequently used medication types associated with increased morbidity  while also more intelligently targeting the sensory systems associated with the pain, thereby reducing the use of high cost healthcare resources  in the name of evaluating or treating chronic abdominal pain.If the studies described above further substantiate the link between NaEG-L helped to develop some of the conceptual framework for this study, performed the TaqMan sequencing experiments, and undertook some of the genetic analyses and was a key author and editor of this manuscript. YI helped develop the probes used for targeted exome sequencing, provided regular conceptual consultation, and helped to write and edit the manuscript. VW and LZ helped to select and perform the statistical tests and reviewed the manuscript. WK and XH provided the blood samples and patient data evaluated in this study and both reviewed the manuscript. KV and MC developed the major framework for this study, performed the primary analyses associated with this investigation, and were key, equal authors, and editors of this 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.


Little is known about the impact of bone graft harvesting for pre-implant augmentation of the maxilla from a patient’s perspective. To assess patient-reported outcome measures (PROMs) related to augmentation of the extremely resorbed edentulous maxilla with calvarial or anterior iliac crest bone.n = 10) or anterior iliac crest (n = 10) bone harvesting. Patient reports on procedure-related satisfaction, questionnaires on oral functionality  and oral health-related quality of life (OHIP-49NL) and subjective donor site-related outcomes  were assessed.For this randomised controlled trial, 20 consecutive edentulous patients needing extensive pre-implant surgery of the maxilla were randomly assigned to either calvarial (p = 0.400) with the procedure and its final results. Post-operative pain was mild (median 40 (20–40) mm) and decreased to no pain (4 (0–16) mm) within 14 days. Early post-operative pain was significantly higher following anterior iliac crest harvesting (p < 0.00). Impact on physical mobility, daily functioning and satisfaction with the scar formation were similar in both groups.Irrespective of the harvesting site, patients were generally satisfied (median VAS score 93 (86–99) mm, The assessed PROMs confirmed that bone graft harvesting from the calvarium or anterior iliac crest is an appropriate procedure, reflected by high levels of satisfaction, minor long-term sequela and improvement of perceived oral health. For clinical decision-making, decisions can be based on individual features and preferences.NTR3968, registered 1 July 2013.NTR,  Pre-implant augmentation of the maxilla using extraorally grafted bone has been studied objectively on medical indicators, such as surgical complication rate, donor site morbidity and physical characteristics –4. LittlThe use of objective outcome measures strikes to the modern view on clinical research that appropriate judgments on the outcome of therapeutic procedures come from those who experience them from beginning to end, i.e. the patients themselves . Hence, PROMs have shown that an edentate state is associated with a significant decrease in oral health-related quality of life (OHRQoL) , 14 and A total of 20 consecutive eligible patients was asked to join the study. These patients were referred to the Department of Oral and Maxillofacial Surgery of the University Medical Centre Groningen (UMCG), Groningen, the Netherlands, having problems with wearing an upper denture . These problems were a result of severe resorption of the edentulous maxilla. Patients were included when insufficient bone volume was available for reliable implant placement, that is, < 3 mm bone height in the maxillary sinus area and < 2 mm bone width in the anterior maxillary area. The bone height and width were assessed using cone-beam computed tomography (CBCT) scanning. For the temporal bone, the thickness in the area between the articular tubercle and the end of the mastoid bone had to be > 5 mm to allow for harvesting calvarial bone. None of the participants had undergone an operation at the donor site before.n = 10) or the anterior iliac crest (n = 10). All patients were subjected to a bilateral maxillary sinus floor augmentation and reconstruction of the width of the maxilla. The surgeries took place between November 2014 and September 2016. Each patient was followed up until at least 12 months.Twenty patients gave written consent to participate in the study. Randomisation software was applied to divide them into two groups based on the location for harvesting the bone grafts: the calvarium , a bevel was created through around the calvarial outer table graft to facilitate its removal with a reciprocating saw. The scraper was used to collect copious amounts of cancellous-like bone. To remove the graft without breaking, parallel saw cuts were made in situ . Next, tAll the operations were performed by the same experienced oral and maxillofacial surgeon at the UMCG. After harvesting the calvarial or iliac crest bone, maxillary augmentation surgery was performed according to the procedure by Raghoebar et al. .Broad-spectrum antibiotics  and non-steroidal anti-inflammatory drugs  were provided for 1 week post-surgery. Patient instructions included a soft diet and chlorhexidine mouth rinse  for 2 weeks. Two weeks after surgery, the dental prostheses were corrected and the patients were allowed to wear them again.A 4-month healing time was considered to be sufficient for reliable placement of dental implants in regions grafted with anterior iliac crest and calvarial bone . TherefoOHRQoL was assessed using the validated Dutch version of the Oral Health Impact Profile questionnaire (OHIP-49NL) –21. ThisPatient-reported denture satisfaction, including functional problem complaints in general, specific features related to facial and denture aesthetics and accidental lip, cheek and tongue biting, were assessed using a validated questionnaire . The patPatients’ eating ability was assessed by a validated chewing ability questionnaire . This quEach patient was asked to score the post-operative pain felt at the donor site during each of the first 30 days after harvesting surgery was performed. A 10-cm vertical visual analogue scale (VAS) score was used, with the bottom anchor representing ‘no pain’ and the top anchor as ‘worst pain imaginable’. Assessments took place at 12 o’clock each day. By measuring the distance (millimetres) on the 10-cm line between the ‘no pain’ anchor and the patient’s mark, the score is determined on a range from 0 to 100. For interpretation of the scores, the following cut points on the pain VAS were used: no pain (0–4 mm), mild pain (5–44 mm), moderate pain (45–74 mm) and severe pain (75–100 mm).A three-item list questioned several aspects of the patient’s experience with the procedure. The patient’s satisfaction with the end result was assessed using a 10-cm VAS scale with the bottom anchor representing ‘very unsatisfied’ and the upper anchor ‘very satisfied’. The other two items questioned (yes/no) whether the patient would recommend the procedure to other patients with the same problem and whether the patient would be willing to undergo the same operation if needed. Furthermore, satisfaction with the outcomes was assessed regarding the scar aesthetics at the donor site (yes/no) and whether the altered donor site contour was bothersome (yes/no).Twelve months after the implant-based prostheses’ were placed, the patients were seen for the final follow-up. They were asked to rate the current pain at the donor site (VAS score). In addition, the patients were questioned regarding difficulties with wearing clothes  and difficulties with functional mobility . Patients were asked whether they had perceived such difficulties during the 7 days prior to the follow-up meeting and whether these problems had been present before surgery. If the latter was positive, the results were excluded from the evaluation. The items were formulated as two-choice questions (yes/no).t test, the Mann-Whitney U test and the Pearson χ2 test compared the outcomes of the parametric variables, nonparametric variables and the categorical gender variable between groups, respectively. Concerning the outcome data, the Pearson χ2 test compared dichotomous variables. For the post-operative pain diary, a mixed ANCOVA was performed. Medians instead of means were calculated for non-normally distributed continuous variables such as the general satisfaction (VAS score) and questionnaire scores. A significance level of 0.05 was chosen for all tests.The data were collected by one observer (ABE). Data management and analysis were performed using SPSS 23.0. Data were tested for normal distribution with a Shiparo-Wilk test and checked visually using a histogram with a distribution curve. If required, the outcomes of a non-normally distributed variable were transformed into a normal distribution using a Log10 transformation. The Student All consecutive eligible patients that were referred to our department between November 2014 and March 2016, and met the inclusion criteria, were willing to join the study. The augmentation surgery resulted in sufficient bone volume for implant placement at the prosthodontically preferred sites in all cases. No peri-operative complications occurred and no additional interventions, such as drain placement at the donor site, were needed. A total of 44 implants was placed in each group. In each group, one patient lost an implant because of mobility during the osseointegration phase, resulting in a 1-year implant survival rate of 97.7%. The clinical characteristics of both groups are listed in Table p = 0.001–0.003, Table U test, u = 34.00–49.50, p = 0.23–0.98, Table The OHIP-49NL sum scores and scores on all seven domains improved between baseline and 12 months post denture placement   at baseline to 11.00  12 months after overdenture placement , meaning the pain scores of anterior iliac crest group are higher than the calvarium group scores .The mean VAS scores for pain ranged from 32.5 ± 17.1 on day 2, which can be interpreted as mild pain, to 3.5 ± 15.8 mm on day 14, interpreted as no pain , and therefore, a Greenhouse-Geisser correction (ɛ = 0.11) was used. There was a significant effect of time on VAS scores, F = 32.6, p < 0.0005.  = 2.9, p = 0.04), but not for the calvarium group  = 0.1, p = 0.93).To determine the effect of time and covariates such as age, gender and BMI on the VAS scores, a repeated measures ANCOVA was run. Mauchly’s test of sphericity indicated that the assumption of sphericity had been violated (n = 20) confirmed that they would undergo the same procedure again if needed and that they would recommend the procedure to others. The overall level of satisfaction with the end result was high with a median of 93  on a 100-mm VAS scale (n = 20).The results on general patient satisfaction are listed in Table U test, U = 34.5, p = 0.247). The VAS scores on satisfaction with the end result contained one outlier (VAS score 4 mm) in the calvarium group. The final appearance of the prosthetic device did not match this patient’s expectations. The complaint was directed at the prosthetic technique and not at the surgical procedure. On excluding this case from the analysis, the remaining scores provided a median score of 93 mm  for the entire study group (n = 19) and 89 mm  for the calvarium group (n = 9). There was no significant difference either when the median VAS scores were compared without the outlier .On separating the results according to treatment group, the median VAS score of the calvarium group was 87 mm  and of the anterior iliac crest group, 95 mm  .Regarding changes at the donor site, one patient from each treatment group noticed an alteration in the contour. Two patients from the anterior iliac crest regarded the scar aesthetics as being acceptable instead of satisfactory   and 2 mm , respectively. (Mann-Whitney χ2 test, p values 0.31–1.00, Table None of the participants in the calvarium group reported difficulties with wearing clothes or functional mobility Table . One parPROMs are a core aspect in treatment programme evaluations . TherefoThis study’s results are in accordance with previous findings in literature on OHRQoL, denture satisfaction and chewing ability, procedure-related satisfaction and long-term donor site-related outcomes . The proAnother previously described phenomenon was found: the surgery comes along with moderate direct post-operative pain and with high levels of satisfaction . High paThis study assessed satisfaction at the final follow-up to assure the patients’ appreciation would entail each step in the treatment programme. However, the course that patients’ satisfaction makes was not registered. Furthermore, not all dimensions of patients’ satisfaction were assessed as this study focussed on the patients’ appreciation of the technical procedure. Future research on these two points can help in improving the treatment programme. Furthermore, it is worth noting that in the current study, the positive PROMs are measured in complete absence of post-operative complications in both groups. As the complication rate for both treatments is low, we consider the results of our study as being representative.To conclude, prosthetic rehabilitation programmes, encompassing maxillary augmentation with extraoral bone grafts from either the calvarium or anterior iliac crest, are reliable pre-implant surgery procedures for extremely resorbed maxilla cases, as they are associated with high patient satisfaction in terms of both treatment procedure and end results. As patient satisfaction is determined by the patient’s expectations and provision of information, an explanation of the procedure and the course of post-operative complaints deserves special attention in clinical practice.


The aim of this study was to explore the prevalence and risk factors for axial neck pain in patients undergoing multilevel anterior cervical decompression with fusion surgery.In this study, 88 patients, who underwent multilevel anterior cervical decompression with fusion surgery from January 2012 to January 2017, were retrospectively reviewed. Based on the postoperative axial neck pain, the patients were classified into two groups: axial pain group and no axial pain group. The patients were followed up 3 weeks, 3 months, and 1 year after cervical anterior surgery for the early- and long-term clinical evaluation. The possible effect factors included demographic variables  and surgery-related variables .P < 0.001) and preoperative kyphosis  were risk factors for axial pain after multilevel anterior cervical surgery. Additionally, for patients with preoperative cervical kyphosis, compared to no axial pain group, the axial neck group was significantly more likely to exist a higher preoperative angle of C2–7  and a higher correction range for kyphosis . However, for all the patients with postoperative axial symptoms, the improvement rate of axial pain was significantly higher for patients without cervical kyphosis at the early-term follow-up (3 weeks) (P = 0.032), no significant differences were found at the medium-term (P = 0.554) and long-term follow-up (P = 0.902), and improvements of clinical symptom have no obvious difference at the last follow-up.The prevalence of axial neck pain was 27.3% (24 cases of 88). Our results showed that preoperative axial neck pain (62% vs 23%, Overall, preoperative axial neck pain and kyphosis could predict axial neck pain for patients undergoing multilevel anterior cervical decompression with fusion surgery, and recovery of cervical kyphosis may contribute to the long-term recovery of neural function, but may also suffer from risk of short-term axial pain, which could be reduced through moderate cervical curvature recovery. Cervical spondylotic myelopathy (CSM) is a common clinical degenerative disease with an incidence of about 53.5% , 2, seriBetween January 2012 and January 2017, a total of 88 consecutive patients (45 men and 43 women) who were diagnosed with multilevel CSM and needed operative managements were examined prospectively. The Ethics Committee of The Third Hospital of Hebei Medical University approved the study, and written informed consents were obtained from all patients before they were recorded. The inclusion criteria were the following: multilevel cervical spondylotic myelopathy of cervical spinal stenosis with neurological dysfunctions; inefficacious patients treated with conservative treatment; and 3- and 4-level anterior cervical decompression and instrumentation including ACCF (2-level corpectomy), ACDF (3- or 4-level), ACHDF (1-level corpectomy plus 1- or 2-level discectomy). The exclusion criteria were the following: the presence of ossification of the posterior longitudinal ligament; the presence of infection and trauma; cervical ossification of the ligamenta flava; association with thoracic or lumbar diseases or spine deformity; previous history of spinal surgery; and unwillingness to participate in the study.The possible risk factors include two parts: demographic variables and surgical-related variables. The following are the demographic variables collected at baseline: age, sex, BMI, smoking, drinking, heart disease, hypertension, diabetes, preoperative kyphosis, preoperative axial neck pain, preoperative JOA scores, and ODI. And the surgical-related variables include the following: surgical option, lesions vertebral, spinal canal stenosis rate, superior fusion segment, and presence of intramedullary high signal intensity.All the patients underwent cervical neutral lateral X-ray film, and the cervical lordosis (CL), namely as C2–7 Cobb angle, was calculated by measuring the angle between the C2 subvertebral endplate plane and the extension line of C7 subvertebral endplate plane at preoperation and postoperation on lateral radiographs. Anterior convex was positive and posterior convex was negative Fig. .Fig. 1ThThe visual analog scale (VAS) is a sensitive and reliable clinical procedure for the assessment of pain degree, which consists of a horizontal line 100 mm in length. The ends of the horizontal line point “0” and “100,” respectively representing “no pain” and “worst imaginable pain.” The middle section shows different degrees of pain . Based ot tests and chi-square. Age, BMI, preoperative axial neck pain, lesions vertebral, spinal canal stenosis rate, preoperative JOA scores, and ODI were analyzed using independent samples t tests, and sex, smoking, drinking, heart disease, hypertension, diabetes, preoperative kyphosis, preoperative axial neck pain, surgical option, lesions vertebral, superior fusion segment, and presence of intramedullary high signal intensity were analyzed using chi-square. The statistical significant value was set at P < 0.05 in the univariate analyses. All statistical analyses were carried out by SPSS software version 13.0 .Comparative analysis with postoperative axial neck pain as the dependent variable was done using independent samples On the day before surgery, 88 patients (45 men and 43 women) were registered on the books for evaluation voluntarily. The cohort of patients was integrated before discharge. At the time of 1-year follow-up, no patient was lost to follow-up. Thus, 88 patients (45 men and 43 women) had entered into the final assessment phase. Based on the postoperative axial neck pain, the patients were classified into two groups: axial pain group, including patients with obvious pain and related pain treatment, and no axial pain group, including patients with no axial pain or with slight discomfort and without treatment.P < 0.001) and preoperative kyphosis  had a significant difference between the two groups , sex (P = 0.542), body mass index (BMI) , smoking (P = 0.430), drinking (P = 0.219), heart disease (P = 0.580), hypertension (P = 0.551), diabetes (P = 0.683), JOA scores , DOI scores  , operation time , surgical option (P = 0.187), superior fusion segment (P = 0.499), incision length , blood loss , preoperative VAS-neck , and presence of IHSI on MRI (P = 0.563)  and a higher correction range for kyphosis  (Table n = 24), the improvement rate of axial pain was significantly higher for patients without cervical kyphosis at the early-term follow-up (3 weeks) (P = 0.032), and no significant differences were found at the medium-term (P = 0.554) and long-term follow-up (P = 0.902) (Table Additionally, for patients with preoperative cervical kyphosis, compared to the no axial pain group, the axial neck group was significantly more likely to exist a higher preoperative angle of C2–C7 (13.31 ± 2.33 vs 7.33 ± 2.56, Degenerative spine diseases such as CSM are increasing among the geriatric population, and surgical treatment of CSM is becoming more common. Consensus has currently been reached on the surgical management of CSM involving one or two mobile segments; however, controversy remains regarding the selection of surgical procedures for treatment of multilevel CSM, especially 3- or 4-level CSM –25. Li eIn this study, radiologic images of the patients showed that spinal cord compressions in the majority of multilevel CSM were mainly the result of protrusive intervertebral discs and osteophytes, and the pathophysiologic features of multilevel CSM make anterior decompression the most effective surgical option. We found that the prevalence of axial neck pain was 27.3% for patients undergoing multilevel anterior cervical decompression with fusion surgery, which was significantly lower than that of posterior decompression. This might suggest that the destruction of posterior cervical muscle complex had a significant effect on postoperative axial symptoms. On the basis of perioperative clinical and radiographic parameters, we compared three different anterior techniques, ACCF, ACDF, and ACHDF, for the treatment of 3- and 4-level CSM. The result shows that different surgical procedures for postoperative axial pain make no difference. The key finding of this study is that preoperative axial neck pain and kyphosis are the risk factors of axial neck pain for patients undergoing multilevel anterior cervical decompression with fusion surgery, and moderate correction of the kyphosis is more significant to avoid the axial pain.The physiological curvature of the cervical vertebrae is an arcuate protuberance in the middle of the cervical segment of the human spine, which evolved over a long period of time to adapt to the upright walking posture of the human body. Lee et al.  pointed This study is associated with several limitations. First, due to its retrospective design, our results did not rule out or compensate the diverse possible causes of postoperative neck pain. Therefore, further study is needed to prospectively evaluate the nature of postoperative neck pain after multilevel anterior cervical decompression with fusion surgery according to the fusion level and the nature and location of neck pain. Second, different people may have different subjective feelings about the same thing because of the different environment. In our study, only a part of all variables were selected to study which may lead to exist selection bias. Third, the effect of other postoperative complications on the postoperative neck pain was not taken into account.Overall, preoperative axial neck pain and kyphosis could predict axial neck pain for patients undergoing multilevel anterior cervical decompression with fusion surgery, and recovery of cervical kyphosis may contribute to the long-term recovery of neural function, but may also suffer from risk of short-term axial pain, which could be reduced through moderate cervical curvature recovery.