Nonrepositioned patients were hospitalized for an average of 4.1 days . There was one complication in the control group requiring screw revision. Lateral interbody fusion and percutaneous posterior instrumentation are both readily accomplished in a single lateral decubitus position. In select patients with adequately sized pedicles, performing simultaneous procedures decreases operative time over sequential repositioning. Patient outcomes were excellent in the simultaneous group and comparable to procedures done sequentially.Lumbar fusion surgery involving lateral lumbar interbody graft insertion with posterior instrumentation is traditionally performed in two stages requiring repositioning. We describe a novel technique to complete the circumferential procedure simultaneously without patient repositioning. Twenty patients diagnosed with worsening back pain with/without radiculopathy who failed exhaustive conservative management were retrospectively reviewed. Ten patients with both procedures simultaneously from a single lateral approach and 10 control patients with lateral lumbar interbody fusion followed by repositioning and posterior percutaneous instrumentation were analyzed. Pars fractures, mobile grade 2 spondylolisthesis, and severe one-level degenerative disk disease were matched between the two groups. In the simultaneous group, avoiding repositioning leads to lower mean operative times: 130 minutes (versus control 190 minutes;  Spinal fusions were conventionally done through open surgical methods via anterior or posterior approaches. With the recent advancements in technology, surgical methods, and imaging techniques, innovative minimally invasive spine surgery has emerged –3. A recLateral interbody lumbar fusion procedures are becoming more common for degenerative lumbar disease requiring instrumentation and they are typically performed by repositioning the patient to complete the second stage of the circumferential procedure , 8. We hThe following technique should be considered in select patients undergoing a minimally invasive lateral transpsoas interbody fusion with a subsequent posterior percutaneous instrumentation. This technical note describes our early experience with this method, our technical nuances, and the potential benefits that it may provide for both the surgeon and the patient.With normal anatomic variances among spine patients, we would tend to avoid this technique in “small or atrophic/dystrophic” pedicles, “rotated, asymmetric” pedicles, or certain L5 pedicles that are difficult to visualize. Additionally, on severe osteoporotic patients with difficult visualization of pedicle anatomy, it is not recommended. Although MIS techniques can be used effectively in larger obese patients, our technique is limited by the fluoroscopic penetrance through soft tissue—which can affect clear visualization of the bony anatomy. On the other hand, in patients with multiple severe comorbidities patients who require several personnel to assist for repositioning, we find that this is a strong consideration for application of this technique.In patients with more than two levels of instrumentation, we have found unique limitations in the instrumentation systems, difficulty with pedicle cannulation, and complexity of rod delivery. As we find no appreciable gain/efficiency in operative time saved, we do not recommend this technique in patients beyond two levels of instrumentation. Avoiding small, atrophic/dystrophic, rotated, asymmetric pedicles. Avoiding morbidly obese if using fluoroscopy. Limiting the procedure to two levels of instrumentation.Complication avoidance with simultaneous lateral interbody fusion and percutaneous posterior instrumentation in the lateral position consisted in the following:Table selection and patient positioning are crucial to the success of this surgical technique. Selection of the ideal operating table is typically one with multiplane adjustment capabilities for use after the patient is secured to the table (Sliding Skytron or breakable Jackson table). In our practice, we utilize a sliding Skytron table with a kidney bump. Before the patient is transferred to the operative table, a “reverse” of the orientation is made so the foot of the table is at the head anesthesiologist location. The table is also slid to the farthest extent to keep the base of the table at the anesthesiologist head—away from the operative field. This allows easy introduction of the mobile fluoroscopy unit and seamless transition between the AP and lateral planes.Once the patient is turned in the lateral decubitus position, an axillary roll is inserted and all pressure areas are padded. The arms are positioned away from the abdomen, and the patient's thorax and pelvis/lower extremities are tapped to the table—aligning the greater trochanter to the break in the table. The table is then adjusted using fluoroscopic guidance to achieve the ideal visualization for the disc spaces and bony pedicles.A specific note is made to placement of the lateral decubitus patient beyond the lateral edge of the table as much as possible (towards the surgeon's side). The dorsal lumbar soft tissue should be hanging over the lateral table and beyond a line drawn from the lateral edge of the OR table. This technical pearl is emphasized in order to achieve enough room for a lateral-medial trajectory for cannulation of the pedicles closest to the floor. We have found that if the patient's dorsal spine does not adequately hang over the lateral edge of the operative bed, then potentially the surgeon will be blocked by the OR table/mattress leading to a potentially unwanted lateral-based screw trajectory.The lateral flank and posterior spine are prepped and draped in one contiguous fashion. Oftentimes, two iodine-impregnated adhesive skin barriers are required. A note is made to completely prep and drape out the entire dorsal posterior lumbar spine.To localize the incision, a perfect lateral fluoroscopic image is obtained centered over our desired disc space. Previous reports have identified ideal starting points for each lumbar disc in relation to the lumbar plexus anatomy . A singlA neuromonitoring electrical stimulation probe is guided down to the psoas with finger retraction of the peritoneal contents. A lateral fluoroscopic image is used to guide our probe trajectory. With free-running EMGs, the stimulated probe is used to traverse the psoas muscle and enter the disc space. Care is taken not to injure the lumbar plexus or associated nerve roots. Serial dilators and specialized illuminated retractors are deployed and the discectomy and interbody insertion are completed. Throughout the procedure neurophysiologic electromonitoring is utilized. unchanged for the second-stage posterior procedure. Implant selection for this technique is helpful as instrumenting a lateral decubitus patient requires an additional level of difficulty and spatial orientation. Recommendations are made to utilize MIS instrumentation systems that allow for “guided” insertion of the rod to the pedicle screw reduction towers. In our experience, for one- to three-level fusions, guided MIS rods  offer the ability to insert percutaneous rods into pedicle screw reduction towers with ease and without significant soft tissue difficulty  and compared the outcomes with a control group of ten patients who underwent the lateral interbody fusion and were then repositioned for posterior percutaneous screw fixation (repositioned). Across both groups, patients were matched for by age and reason for surgery. In both groups, pars fractures with instability (4), mobile grade two spondylolisthesis (4), and the remaining patients had severe degenerative disk disease at a single level (12). Indications for surgery included worsening back pain in patients who failed exhaustive conservative management.A 47-year-old male presented with end-stage degenerative disc disease at L2/3 with associated severe back pain and bilateral lower extremity radiculopathy that had failed an extensive course of nonoperative management. Advanced imaging, including CT and MRI, revealed a grade 1 degenerative spondylolisthesis with associated facet arthrosis. Due to the collapse of the disc space, MRI demonstrated lateral recess and foraminal narrowing with neural stenosis but no acute herniated nucleus pulposus or severe ligamentum hypertrophy. Intraoperatively, the patient was placed in a right lateral decubitus position with the left flank and posterior dorsal spine prepped and draped in one setting. He underwent an L2/3 left lateral transpsoas discectomy and interbody fusion, followed by posterior percutaneous fixation without repositioning. Postoperative films were adequate , and he p < 0.05) and intraoperative blood loss was 108 mL . The nonrepositioned group included 3 women and 7 men, while the repositioned group included 6 women and 4 men. The average age was 54.5 years  and 57.8 years . Avoiding repositioning, operative time from incision to closure averaged 130.5 minutes  was one of the first lumbar interbody surgeries performed . As an aIn the years following the introduction of the PLIF, reports about the ALIF's surgical strain and patient morbidity began to emerge , 24. Thi2 gas insufflation, and possibility of bowl perforation [The 1990s saw pioneering alterations to lumbar spine fusion methods. Indeed, these new techniques would catapult spine surgery into the minimally invasive surgical era. In the earlier part of the decade, the laparoscopic and mini-open modifications of the ALIF were introduced . While tforation . Additioforation , 6. Overforation . Key plaIn 1998, McAfee et al. published on a minimally invasive microsurgical retroperitoneal lateral approach that would lay the foundation for the direct lateral interbody fusion . With a The extreme LIF was initially presented by Pimenta in 2001 as a variation on the retroperitoneal approach to the lumbar spine . It provThe minimally invasive retroperitoneal transpsoas lateral approach is becoming more popular among spine surgeons , 34. SinWith modern technological advances in surgical techniques, imaging modalities, bone graft alternatives, and attempts to decrease patient down time, spine surgery has seen a tremendous shift into the realm of minimally invasive surgery over the last 20 years –3, 9. FrThe technique described in this paper is to be considered for select patients undergoing a minimally invasive lateral transpsoas interbody fusion approach with a concomitant posterior percutaneous instrumentation. Our recommendation on the feasibility of this technique for a given patient is primarily determined by patient's bony anatomy, body habitus, and the number of levels fused. Pedicles for instrumentation should be large and clearly visualized on radiographs. Additionally, imaging of this anatomy may be affected abundance of soft tissue, a limitation in obese patients. Finally, the benefits of the procedure are not appreciated beyond two levels of instrumentation, and thus we do not recommend it.A limitation of this study is that all pedicle screws that were placed in the lateral position were performed at a single center; thus the results need to be confirmed in a multicenter study. It is theoretical that the learning curve of this technique is commensurate with surgeon experience and that the combination of the senior surgeon's advanced experience and efficient workflow may explain the comparable excellent outcomes. In addition, there was no comparative radiographic review of lordosis between the repositioned and nonrepositioned patients. In that realm, a recent review by Yson et al. questioned whether prone-repositioning was necessary to gain the needed lordosis from posterior fixation following LIF . In overSimultaneous lateral interbody fusion and percutaneous posterior pedicle screw fixation avoided repositioning, shortened operative time. Combining both procedures into a single lateral position also maintains surgical precision with comparable excellent outcomes. We are hopeful that this novel technique will contribute to the advancement of modern, minimally invasive spine surgery.The lateral interbody fusion and percutaneous pedicle screw procedures can both be accomplished in the lateral decubitus position. In select patients with adequate size pedicles, performing simultaneous procedures offers an advantage over sequential surgery requiring repositioning. Performing the surgeries together accomplished a circumferential fusion with increased stability over each procedure performed alone. Patient outcomes were excellent and comparable to procedures done in series.


Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in the community pharmacy. Their systemic administration has been related to significant adverse effects. The aim of this study was to evaluate the efficacy of topical NSAIDs in managing mild to moderate musculoskeletal pain versus systemic administration or combination of both routes.This was a prospective observational study conducted in a large Lebanese community pharmacy over a period of 5 months in 302 patients. Participants were divided into three groups according to their route of administration of NSAIDs either topically, systemically or combination of both. During follow up period, degree of pain, efficacy of NSAID therapy, side effects, onset time and duration of pain relief reported by each patient were collected by the study investigators using specific formulated questionnaire. Degree of pain was assessed using the Numeric Rating Scale (NRS-11). The efficacy of NSAID therapy was defined as 50 % reduction or more in pain. The primary outcome was to assess the efficacy between groups. The secondary outcomes were onset time, duration of pain relief and side effects between the three groups.A total of 149 patients were enrolled in this study. 78 patients administered topical NSAIDs, 40 administered systemic NSAIDs and 31 administered combination of both routes. Efficacy of NSAID therapy for all routes was reported in 132 participants (89 %) distributed as 64 in topical, 37 in systemic and 31 in combination. Bi-variate analysis showed no significant difference in efficacy between topical versus systemic (p = 0.99) and topical versus combination (p = 0.14). The mean onset of topical NSAIDs was significantly faster than systemic by 12.7 min (p < 0.05). The mean duration of pain relief of systemic NSAIDs was significantly longer than topical by 3 h (p < 0.05). Patients administered systemic NSAIDs  reported increase in blood pressure and gastric-upset 8 and 38 cases, respectively.There was no significant statistical difference between NSAIDs route’s of administration for the treatment of mild to moderate musculoskeletal pain in Lebanese community pharmacy patients. Topical NSAIDs were fast in onset and effective in reducing pain with no significant adverse effects. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are among the most commonly used and effective medications to treat musculoskeletal conditions because of their anti-inflammatory and analgesic effects , sub-acute (7–12 weeks of symptoms) or chronic (more than 12 weeks of symptoms)  , site of pain, used analgesic in the last month, NSAID parameters , concomitant medications , co-morbid diseases , history of previous gastrointestinal bleeding due to NSAIDs, and hypersensitivity to NSAIDs/aspirin. Patients who met the inclusion criteria were divided into three groups according to their NSAID’s route of administration including topical , systemic  and combination of both topical and systemic dosage forms.All patients were followed up by the primary investigator on Day 3, D6, D10, D14, Week 4, W8 and W12 through phone calls or scheduled pharmacy visits. Follow up was terminated when the patient discontinued the NSAID treatment for a certain reason . During follow-up dates, the primary investigator counseled the patients about proper use of NSAIDs in terms of dose, frequency, and route of administration. Degree of pain, efficacy of NSAID therapy, onset time of pain relief (estimated in min), duration of pain relief (estimated in h) and side effects  were reported by each patient and collected by the study investigators using specific formulated questionnaire “AD-23.16.14”. All patients were asked about their therapy satisfaction, medication adherence, and add-on analgesics other than NSAID. Total duration of therapy was also recorded at the end of the treatment.Since our data collection methodology involves structured interview we obtained a signed informed consent form before starting the study. The consent form explained that all data will be stored in the School of Pharmacy at the Lebanese International University (LIU). Copies of the informed consent were kept as data research records in LIU School of Pharmacy. All data that is collected from our study has the potential to be shared publically. Consequently, to maximize benefits and minimize harm, investigators explained to all participants that any acquired information is to be treated with confidentiality and published results are to be in aggregate form with no reference to names.Descriptive statistics were used to describe patient characteristics , and mean (±SD) for continuous variables.Bi-variate analysis and cross-tabulation were used to identify the significance between different routes of administration and the efficacy of NSAID treatment. One way analysis of variance (ANOVA) test was performed to identify whether there is difference in onset time and duration of pain relief among the 3 groups. Statistical significance was defined as p value <0.05. Statistical analyses were performed using the Statistical Package for Social Science (SPSS version 20.0 IBM).A total of 302 patients were initially screened, 153 patients (50.6 %) were excluded for the following reasons: severe musculoskeletal pain (20 %), neuropathic pain (12 %), headache (10 %), study participation refusal (8 %) and cancer pain (0.6 %). The remaining 149 (49.4 %) patients were enrolled and followed up in this study  followed by sub-acute (25 %) and chronic (8 %). Co-morbid diseases were reported by the participants at baseline such as hypertension (30 %), coronary artery disease (15 %), diabetes (8 %) and peptic ulcer disease (8 %). Consequently, anti-hypertensives (33 %), proton pump inhibitors (23 %), anti-lipidemics (16 %) and anti-diabetics (9 %) were used by the participants.Co-analgesics were used in addition to NSAID therapy by a total of 39 patients, of which 20 used muscle relaxants, 12 used acetaminophen and 7 used vitamin B complex supplements.Back pain was the most common site of musculoskeletal pain as reported by 42 patients (28 %), followed by shoulder (18 %), leg (10 %), neck (9 %), ankle (8 %), hand (4 %), knee (4 %), finger (3 %) and elbow pain (2 %).A total of 76 patients (51 %) had a prescription of diclofenac, followed by ketoprofen 45 (30 %), aceclofenac 37 (25 %), naproxen 18 (12 %), piroxicam 4 (2 %) and etoricoxib 1 (0.5 %).The overall efficacy rate of NSAID therapy in mild to moderate musculoskeletal pain was reported in 132 patient out of 149 (89 %), distributed as 64 out of 78 patients (82 %) in topical, 37 out of 40 patients (92 %) in systemic, and 31 out of 31 patients (100 %) in combination group as shown in  in the topical, 30 min (±10.3 SD) in the systemic and 14.5 min (±3.87 SD) in the combination NSAID therapy group. Topical NSAIDs were significantly faster than systemic NSAIDs by 12.7 min with p value of the mean difference <0.05, but slower than in combination group by 2.8 min with p value = 0.28. The mean onset of pain relief in combination therapy was significantly faster than systemic by 15.5 min with p value of the mean difference <0.05 (Table The mean duration of pain relief was 10 h SD ± 3.74) in the systemic, 7 h (SD ± 3.46) in the topical and 11 h (±2.05 SD) in the combination NSAID therapy group. The mean duration of pain relief in systemic NSAIDs group was significantly longer than topical by 3 h with p value of the mean difference <0.05, but shorter than combination therapy by 1 h with p value of the mean difference = 0.85. The mean duration of pain relief in combination group was significantly longer than topical group by 4 h with p value of the mean difference <0.05  reported increase in blood pressure and gastric-upset 8 and 38 cases respectively. Whereas patients who administered topical NSAIDs reported mild transient local dermatological side effects, such as dryness, itching and stinging 2, 3 and 2 cases respectively Table .Table 4RIn this study, NSAIDs showed to be effective in the treatment of mild to moderate musculoskeletal pain by 89 %. Roelofs et al.  study haThe primary outcome of this study was to assess the efficacy of various NSAIDs routes in musculoskeletal pain. When efficacy of NSAID therapy was compared among the 3 groups, all patients (100 %) in the combination group had efficacy of NSAID therapy, followed by 92 % in the systemic group and 82 % in the topical group. Bi-variate analysis and cross-tabulation showed no significant difference between the 3 groups in term of efficacy with a p values of 0.99 between topical versus systemic group and 0.14 between topical versus combination group. Three clinical trials, with 764 patients, compared topical NSAIDs with oral NSAIDs . The overall efficacy rate was similar for topical NSAIDs (37 %) and oral NSAIDs (37 %) with no statistically significant difference  compared to systemic therapy (mean = 30 min), this could be due to the direct and local effects of topical dosage form on the affected area. Duration of pain relief in systemic NSAIDs group (mean = 10 h) was significantly longer than topical NSAIDs group (mean = 7 h) this could be explained by the accumulation of NSAID in the synovial fluids and soft tissues, that would increase the time to clear the drug from these sites. What is important about combination of both NSAIDs routes that it combined the fast onset of topical and the long duration of pain relief of systemic NSAIDs and ended up with a remedy of rapid onset (mean = 15 min) and extended duration of action (mean = 11 h).The addition of other analgesics like acetaminophen, muscle relaxants and vitamin B complex were reported. These co-analgesics interfered with the efficacy of the NSAID treatment and could be considered as confounding variables. It was noted that vitamin B complex and muscle relaxants were frequently administered in the systemic group, whereas acetaminophen was mainly taken in the topical NSAIDs group.In our study, systemic side effects such as increased blood pressure and gastrointestinal upset were reported in 8 and 38 participants respectively, these participants were taking NSAIDs systemically either alone or in combination. Surprisingly, the rate of these systemic side effects was lower in the combination group compared to systemic group; this could be explained by the lower doses and frequencies of the used systemic NSAIDs when combined with the topical NSAIDs. A study done by Miyatake et al.  showed tWe found that most of the patients had applied topical NSAIDs for a total of 10 days, those patients reported high rates of efficacy and mild self limited local adverse events described as dryness, itching and stinging. Similarly, Baer et al.  and BookThis is the first descriptive study that was specifically designed to assess the efficacy, onset time of pain relief and duration of pain relief of topical, systemic or combination of both routes of NSAIDs in Lebanese community pharmacy patients.One of the major limitations was the patient’s assessment of pain, since it is a personal feeling and it could vary between subjects. Another limitation of the study was the use of different NSAIDs agents for a short period of time; consequently many long term outcomes couldn’t be analyzed, this would explain the findings of few side effects of the NSAID therapy especially the systemic ones in the combination group. Baseline characteristics and classification of the participants into three groups further decreased the sample size and affected the results. Additionally, the study was conducted at one community pharmacy in Lebanon which also justifies the small number of enrolled patients in this study and the inability of results generalization. It would therefore be recommended to conduct additional studies including large sample size of patients taking NSAIDs for long period of time for the treatment of musculoskeletal pain in all areas of Lebanon.NSAIDs are the cornerstone of musculoskeletal pain treatment, but their systemic use may be limited in certain patients due to their potential adverse effects. According to our study, there was no significant statistical difference of efficacy between topical, systemic or combination of both routes of NSAIDs in the treatment of mild to moderate musculoskeletal pain in Lebanese community pharmacy patients. Topical NSAIDs were fast in onset and effective in reducing pain with no significant systemic adverse effects. Combination of topical and systemic NSAIDs routes showed faster onset and long duration of pain relief, but it was associated with systemic adverse effects. What remains unclear is the safety of NSAIDs combination of both routes. Additionally it was uncertain if topical NSAIDs remain safe and retain their efficacy on the long term. Thereby, additional large-scale, long-term studies in patients with musculoskeletal pain are needed to identify the role of topical NSAIDs when combined with oral NSAIDs.


Intranasal fentanyl provides rapid and powerful analgesia which is particularly interesting in patients without intravenous access. We propose to use it for analgesia in adults presenting renal colics.A prospective study was conducted from the 2nd January to February 2013 in our emergency department. Patients aged up to 18 years old who presented with renal colic were included in this audit. Patients were excluded if they had loss of consciousness, cognitive impairment, acute or chronic nasal problems. A formal written consent was obtained from patients. The research team was alerted by medical and nursing staff. A member of the research team would check with medical or nursing staff whether administration of Intra nasal (IN) fentanyl was required. It was administered at a pre-calculated dose of 1.5 mg/kg and 50 mg/ml concentration was used. Data was prospectively collected by one of the researchers at various intervals during the patient's presentation and recorded on a pre-formatted data sheet. Pain scores were collected at 5, 15, 30, 45 and 60 minutes following IN fentanyl using a visual analogue scale pain. Observations routinely collected for patients receiving IV opiates and any adverse events were also recorded.23 eligible patientswere enrolled; median age was 51,3years. 47,8% were women and the mean weight was 73 kg. Median dose of IN fentanyl was 106 μg. Two patients have required morphinic analgesia despite having received adapted dose of IN fentanyl. The initial pain scores before IN fentanyl were high with a median of 82,2 mm (59-100). Five minutes after IN fentanyl administration the median pain score dropped to 48mm(36-63) and achieved the lowest score of 8mm(0-22) at 30 min. Pain scores were significantly lower at 5 min (P < 0.001) and at all subsequent time points (P < 0.001). No side effects were recorded.Intranasal fentanyl seems to be efficient for analgesia in adult patients with renal colic. Renal colic is an intensely painful condition requiring rapid analgesic treatment. Opioids are commonly used intravenously to provide rapid pain relief. The objective of this study was to determine the analgesic efficacy and safety of intranasal single dose of fentanyl for patients presenting to the emergency department with renal colic.A prospective study of patients presenting with renal colic was conducted in the emergency department of the military hospital of instruction Mohammed V Rabat where an annual census of 30000 attendances are recorded. Enrollments were made from 2nd January 2013 to February 2013. Adults aged more than 18 years with acute flank pain due to renal colic were included in the study. Exclusion criteria were known allergy, contraindication to morphine, or any opioid analgesic; hemodynamic instability; fever (temperature ≥38°C (100.4°F' > 100.4°F)); evidence of peritoneal inflammation; documented or suspected pregnancy; known or suspected aortic dissection or aneurysm; use of any analgesic treatment within 6 hours before presentation to the Emergency Department; or previous study enrollment. Patients with known renal, pulmonary, cardiac, or hepatic failure, as well as those with renal transplantation, were also excluded. Patients were enrolled 24 hours a day and 7 days a week during the study period. Study eligibility was confirmed by a senior emergency medicine resident. Verbal consent was obtained from patients. Written consent was not obtained to minimize “time to analgesia” in the setting of acute extreme pain. Patients were given intranasal fentanyl at concentration of 50μg/ml and a dosage of 1,5μg/kg. Advantages of this concentration solution are standard availability in all Emergency Departments and lower cost. The intranasal solution was delivered via an atomizer . Assessment of pain, using a 10 mm intervals visual analog scale pain (VAS), was performed at 5, 15, 30, 45 and 60 minutes following IN fentanyl. If the visual analogue scale was still over 4 after the first 5 minutes, we used intravenous morphine to procure quick relief. Data was prospectively collected by one of the researchers and recorded on a pre-formatted data sheet. During the study period, routine observations were noted in accordance with our institution's nursing protocols for the administration of narcotics. Parameters included were blood pressure, pulse rate, respiratory rate, and oxygen saturation every 5 minutes. Adverse events were also recorded. Comparison of patient assessed pain scores collected at 5, 10, 15 and 30 min following IN fentanyl administration were completed using the Wilcoxon signed-rank test. P values are 2 sided and were considered statistically significant if less than 0.05. All analyses were performed using the SPSS program .23 eligible patients were enrolled; median age was 51.3 years. 47.8% were women and the mean weight was 73 kg. Median dose of IN fentanyl was 106 μg. Two patients required morphinic analgesia despite having received adapted dose of IN fentanyl. The initial pain scores before IN fentanyl was given were high with a median 82,2mm (59-100) . Five miIntranasal opioid administration has been studied widely in postoperative patients , 2 and bThe intranasal fentanyl can be a good option for analgesia in case of renal colic because it provides a quick pain relief and its use is safe. Confirmation of its benefits requires studies on larger cohorts.


Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache. In its 2010 Global Burden of Disease Survey, the World Health Organization reported tension-type headache (TTH) and migraine as the second (20.1%) and third (14.7%) most prevalent disorders in the world, exceeded only by dental caries [While such a commonplace condition may be easily dismissed, the impact of headache is not to be taken lightly. Using “years living with disability” as a measure of disease impact, the WHO rated migraine as the 7th most disabling of all 289 diseases surveyed  . In condUnfortunately, the mechanisms responsible for the development of chronic headaches remain unknown. Barring rare exceptions such as “new daily persistent headache,” most patients with chronic headaches initially experience only episodic attacks . While iThanks to recent advances in electrophysiology and neuroimaging, now we are able to test these hypotheses directly on the human brain. In this review, we first provide a narrative overview of the most common forms of chronic headaches and then discuss the neural plasticity underlying specific headache disorders by comparing available electrophysiological and neuroimaging studies in their episodic and chronic forms, according to the tools used and the hypotheses proposed. Emphasis will be laid on migraine as it is the most well studied type of these headaches.Although it is not the most common of the headache disorders we will discuss, migraine headache is by far the most disabling and most researched condition . AccordiCH is a primary headache disorder characterized by severe, strictly unilateral pain, lasting from 15 to 180 minutes .TTH is the most common type of headache . Unlike MOH results from regular overuse of abortive medication, exceeding 10 or 15 days per month , for more than 3 months . While MSensitization of the trigeminal pain network  has been proposed to underlie migraine pathophysiology. As shown by the animal studies conducted by Burstein and colleagues, applying brief chemical stimulation with inflammatory agents to the dura in rats led to peripheral sensitization of the first-order neurons in the dorsal root ganglia of C2/C3 and trigeminal ganglion and central sensitization of the second order neurons in the trigeminal nucleus caudalis . As a result, the rats treated with inflammatory agents had increased excitability in response to brush or nonnoxious heat stimulation –58. ThisElectrophysiological studies of trigeminal processing also characterize neural plasticity in association with CH , althoug2 laser stimulation over the pericranial zone leads to a higher amplitude of the N2a-P2 complex together with a higher degree of pericranial muscle tenderness in patients with chronic TTH than in controls [In TTH, evidence is mounting in support of a neural plasticity characterized by central sensitization. An intriguing study in patients with chronic TTH showed increased suprathreshold pain sensitivity both in skin and in muscle, and in both cephalic and extracephalic regions . This gecontrols .Neural plasticity in the pathogenesis of MOH has also been linked to sensitization. Using SSEP, studies have shown an increase in the amplitude of painful and nonpainful cortical responses, with the latter normalizing following recovery from MOH , 21, 74.Habituation refers to “a response decrement as a result of repeated stimulation” , and patResearch also suggests that changes in habituation may be associated with the transition from EM to CM. Habituation studies using nonpainful somatosensory evoked potentials (SSEP) have reported similarities between the electrophysiological patterns of ictal EM and CM, including initial excessive cortical activation followed by normal habituation during stimulus repetition . Aurora A lack of habituation in the blink reflex on the affected side has been observed in episodic CH patients , 85, 86.Moreover, MOH patients have also shown deficient habituation mechanisms during contingent negative variation  and laseThe role of the central nervous system in pain is not limited to the processing of nociception from the periphery to the higher order regions of the brain; rather, the central nervous system is capable of actively modulating pain perception through descending pain modulatory mechanisms. Among the oldest theories of central inhibition, spinal gate control theory posits a top-down mechanism operating from the cortex to modulate the responses of dorsal horn neurons in the spinal cord . DiffuseTo date, a number of studies have shown vastly altered endogenous pain modulation in migraine patients. In the first exploration of DNIC dysfunction associated with migraine, researchers used the cold pressor test as a conditioning stimulus and assessed the nociceptive flexion reflex . As expeAs we saw with habituation, changes in DNIC may also be associated with the transformation from EM to CM. Using capsaicin as a conditioning stimulus, research has shown increased R2 area of the blink reflex in CM sufferers, as compared to their EM (with aura) counterparts . The resFunctional neuroimaging has played a remarkable role in elucidating the pathophysiology of migraine, from demonstrating that hypoperfusion and cortical spreading depression are the underlying mechanisms of visual aura , 103 to Significant efforts have also been made to link migraine to abnormalities in functional connectivity measured by resting-state fMRI (rs-fMRI). Unlike experiments examining brain responses to stimuli , functional connectivity experiments instead look for concurrent fluctuations of the fMRI signals during a task-free rest period . This liWhile some of the abovementioned experiments have been conducted exclusively with CM patients, many of the studies in the literature have been limited by their inclusion of both chronic and episodic migraine patients. Among those that have focused on CM, a combined electrophysiology and PET study noted increased cerebral metabolism in the brainstem . A rs-fMJust like migraine, recent years have seen many neuroimaging studies probing the etiology of episodic and chronic CH. Early PET studies provided evidence of activation in the ipsilateral hypothalamus, contralateral thalamus, anterior cingulate cortex, and bilateral insulae in CH , 114, wiNeuroimaging studies have provided valuable information on neural plasticity underlying MOH as well. An early PET study provided evidence of hypometabolism in the orbitofrontal cortex that persisted after detoxification, implying that the dysfunction observed is the cause, rather than a consequence, of MOH . An fMRIStudies from a wide variety of chronic pain conditions, including chronic back pain , fibromyThe mechanisms underlying structural changes in the brain associated with migraine remain to be determined. Based simply on the similarity of findings between migraine studies and those of other headache subtypes and other pain disorders, it has been proposed that these changes are consequences rather than causes of repeated attacks . One potAnother technique used to evaluate structural alteration in patients with migraine and other pain disorders is surface-based morphometry, a technique that allows the measurement of cortical thickness instead of volume . It is wIn line with these observations, two early studies by Hadjikhani and colleagues reported increased, rather than decreased, cortical thickness in the somatosensory and visual motion areas in patients with EM , 39. A sStructural imaging studies of CH also have had mixed results, disagreeing not only on the brain regions affected, but even on the direction of grey matter volume changes. Using VBM, a pioneering structural imaging study revealed gray matter volume increases in the bilateral posterior hypothalamus, a region colocalized with the functional changes observed in PET imaging of CH . ExaminiReversibility of morphological changes has been reported in other chronic pain conditions, including a recent surface-based morphometry study  demonstrDecreases in gray matter volume of pain-related brain structures were also reported in patients with chronic TTH, including anterior cingulate cortex, insula, orbitofrontal cortex, parahippocampal gyrus, and dorsal rostral pons . These dIn MOH patients with migraine history, significant gray matter volume decreases were reported in the orbitofrontal cortex, anterior cingulate cortex, insula and precuneus, as well as volume increases in the periaqueductal gray, thalamus and ventral striatum . The samWhile the clinical significance is unclear, migraine patients have well-documented white matter hyperintensities . To explAnother promising line of research in the study of the neural mechanisms underlying chronic headache or pain disorders is represented by the use of magnetic resonance spectroscopy (MRS). MRS allows noninvasive and in vivo exploration of the molecular composition of tissue, by identifying certain metabolites involved in physiological or pathological processes. By using techniques such as single voxel spectroscopy or chemical shift imaging, researchers were able to reveal the presence of biochemical alterations in the brain of patients with various chronic pain disorders. For instance, studies have demonstrated a reduced concentration of N-Acetylaspartate (NAA), a marker of neuronal integrity in chronic low back pain –156, com1H-MRS metabolite ratios in EM and CM patients [Despite the great potential, not many MRS studies have been conducted in migraine patients. Of those that have been conducted, the majority focus on disturbed energy metabolism, indicating a possible role of mitochondrial dysfunction in migraine pathophysiology . Anotherpatients . PatientGenes may influence the cerebral processes that lead to the progression from episodic to chronic headache and determine distinctive morphofunctional properties . Most stThough few in number, studies have been conducted to examine whether select gene polymorphisms might influence neural plasticity (habituation/sensitization) in MOH. The angiotensin-converting enzyme D/D genotype appears to serve as an influencing factor in migraine attack frequency , as wellConsidering that MOH bears resemblance to an abuse disorder and that previously identified susceptibility genes, such as the angiotensin-converting enzyme polymorphism, have also been linked to substance abuse behavior, researchers have sought to examine whether there are psychiatric differences between MOH sufferers with various polymorphisms. Researchers have examined whether the brain-derived neurotrophic factor (BDNF) Val66Met and wolframin His611Arg (WFSI) polymorphisms, both being linked to psychiatric illness and dependence behavior, might be related also to MOH. They observed that individuals carrying the RR WFSI  and the Others have taken an epigenetic approach with the hopes of assessing whether gene expression patterns may change along with patients' migraine state. Hershey et al. , 177 fou∗1F variant, both enzymes responsible for triptan degradation [Genetic linkage studies have reported a significant association between CM and the long allele of monoamine oxidase A 30 bp VNTR and CYP1A2radation . The latradation . Knowingradation . Allele radation .In summary, inheritance appears to play an important role in determining predisposition to specific clinical manifestations of migraine and the progression to CM, especially when related to MOH. Furthermore, the association between gene polymorphisms and characteristic neurophysiologic patterns in CM suggests that genetics can influence the way the brain responds plastically to chronic head pain and excessive drug consumption.To date electrophysiological and neuroimaging studies have revealed different aspects of neural plasticity associated with chronic headaches, especially migraine. Other common forms of chronic headaches, such as chronic CH and chronic TTH and MOH, also share some features of neural plasticity with CM, notably changes in brain excitability . NeverthNeural responses to episodic headache are initially adaptive and physiologic but later become maladaptive and pathologic, eventually creating a vicious cycle resulting in chronic headache. This process of headache evolution is associated with neural plasticity in brain excitability, biochemistry, function, and even structures. Genetic factors are likely to contribute to this process. Further studies are needed to elucidate if there are common features of neural plasticity among various chronic headaches that may serve as neurologic signatures for chronic headaches, or conversely, headache-specific neural plasticity that may help in the diagnosis and treatment of different chronic headaches.


Linear headache (LH) has recently been described as a paroxysmal or continuous fixed head pain restricted in a linear trajectory of 5–10 mm in width, linking one endpoint in occipital or occipitocervical region with another endpoint in ipsilateral nasion or forehead region. For some patients, this headache had some features resembling migraine without aura.We made a prospective search of patients presenting with a clinical picture comprised under the heading of LH and we have accessed eight new cases. A detailed clinical feature of the headache was obtained in all cases to differentiate with cranial neuralgia, paroxysmal hemicrania, cervicogenic headache, nummular headache and migraine.The eight LH patients complained of a recurrent moderate to severe, distending, pulsating, or pressure-like pain within a strictly unilateral line-shaped area. The headache duration would be ranged from 1 h to 2 days or persistent for 1–6 months with recurrent worsening of headaches. For some patients, this headache had couple of features similar to that of migraine pattern, such as accompaniments of nausea, vomiting, and phonophobia, diziness, triggering factors of noise, bright night, resting after physical activity, fatigue, menstruation, and response to anti-migraine therapy.This description reinforces the proposal of LH as a new headache syndrome or a new variant of a previously known headache syndrome, probably of migraine. Linear headache (LH) may represent a new headache syndrome or a variant of migraine as proposed recently based on the clinical features of twelve patients who presented with a paroxysmal or chronic fixed head pain restricted in a linear trajectory linking the occipital or occipitocervical region with the ipsilateral nasion or forehead region , the temporal features (duration and frequency), pain character and intensity at baseline and during exacerbations, and pain accompaniments. The presence of any triggering or facilitating factors or interictal symptoms was also evaluated. A complete physical and neurological examination was performed in all cases. Inspection, palpation and sensory examination of the affecting area, as well as palpation of the supraorbital, infraorbital, minor occipital and greater occipital nerves were included in the examination. Routine blood work-up with erythrocyte sedimentation rate, computed tomography (CT) or magnetic resonance imaging (MRI) of the head were performed in all cases to exclude any underlying disease. Cervical vertebra MRI or X-ray was also taken in all patients to check out the lesions which may cause cervicogenic headache (CEH) whose pain maps in very rare cases were described as linear area similar to that in LH , which has been proven to be a valid and reliable test of upper cervical movement impairment associated with CEH , eight patients with LH attended our Neurological department at the first Hospital of Anhui Medical University. The demographic and clinical features of our eight patients are shown in Table All patients complained of strictly unilateral paroxysmal or continuous head pain which almost invariably recurred on the same side. Five patients had symptoms on the left and two patients on the right, while the attacks shifted sides in only one patient. All patients reported gradual onset of pain among a linear trajectory of 5 mm to 10 mm in width, linking the occipital or occipitocervical region with the ipsilateral nasion or forehead region. No patient reported radiation or moving of the pain along the linear trajectory. The pain attack duration would be 1 h to 2 days in six patients, but persistent for 1–6 months in two patients of whom one had episode of pain worsening for 1–3 h. The pain character was pulsating or distending in most cases, but pressure-like in one patient and aching pain in another one patient, among these two patients, one also had pulsating feature and another one also distending feature sometimes. The pain character was indescribable in one patient. All patients denied that the pain was epicranial but complained it intracranial. During the attack, accompanied nausea without vomiting was reported in two patients, ipsilateral or bilateral dizziness reported in two patients, ipsilateral or bilateral temporal mild pain in three patients and desire to defecate in one patient, while no accompanied symptom reported in two patients. The paroxysms were usually spontaneous in four cases, but triggered by noise and bright light in one case, by noise and resting after physical activity in one case, by fatigue in one case and by menstruation in one case. During the interictal period, six patients had no symptoms at all, the other two had persistent LH pain. The frequency of attacks was variable, ranging from one attack every 2–3 months to one attack per day. The temporal pattern of the attacks was chronic in four patients who had been having attacks for 1–20 years without a remission. One patient had a remission period of 1 year between recurrent periods. The remaining three patients had short symptomatic period of half to 1 month and the pain was persistent or recurrent every day.With regard to examinations, no skin change was noted along the painful linear trajectory either during the ictal period or during the interictal period in all patients, but a hyperaesthesia to light touch noted along the painful linear trajectory in one patient (patient 2). Regional mild pain was noted in two patients while palpating the greater occipital nerves (patient 2 and 4), but no abnormal sensation noted in all other patients. Neurological examination, brain CT or MRI, and blood tests were normal in all patients. Cervical MRI or X-ray results revealed no special in almost all patients except in one patient (patient 1) who had degenerative changes of cervical vertebra. FRT results were negative in almost all patients except in one patient (patient 1) whose head rotation ranges to both sides were positive .Before coming to our department, 5 out of the 8 patients had ever tried analgesics while the headache was attacking. 2 patients (patient 2 and 3) could not remember what the exact analgesics they had ever taken. 2 patients (patient 1 and 5) had ever tried analgesics consisting of aminopyrine, phenacetin, caffeine and phenobarbital, and the pain was alleviated mildly in one patient (patient 1) but not in another one (patient 5). One patient (patient 4) had ever tried indomethacin and the pain was not reduced. All these 5 patients abandoned the medications after trying couple of times. Regarding therapy after they came to our department, eight patients accepted prophylatic treatment and had good responses. Two patients (patient 6 and 8) treated with flunarizine (5 mg twice a day) alone had the headache recurrence prevented and stopped taking medicine after 1 month treatment. Three months later, the headache recurred in one patient (patient 8). Three other patients  also took flunarizine (5 mg twice a day) alone first, and among these three patients, pain frequency and intensity was reduced in one patient (patient 7), but not changed in the other two patients (patients 1 and 2) who were further added with venlafaxine (from 75 mg once a day to 150 mg once a day) with pain recurrence prevented in one patient (patient 1) and pain frequency and intensity reduced in another one patient (patient 2). Sodium valproate (500 mg twice a day) alone relieved the LH pain in one patient (patient 5) but only reduced the pain severity in another one patient (patient 3) who was then added with flunarizine (5 mg twice a day) and had the non-menstral pain prevented but menstral pain unchanged. For the last patient (patient 4), sodium valproate (500 mg twice a day) alone, sodium valproate (500 mg twice a day) together with flunarizine (5 mg twice a day), or venlafaxine (from 75 mg once a day to 150 mg once a day) alone failed to relieve the pain, but venlafaxine (150 mg once a day) in combination with pregabalin (150 mg twice a day) prevented the LH pain with the occipitocervical point pain left there unchanged.LH is a recently described headache pattern which apparently constitutes a new headache syndrome or a new variant of migraine. Table There are several entities to which differential diagnosis need to be considered. EF, a recently described novel headache syndrome, is characterized by brief pain paroxysms starting in a particular area of the posterior scalp, and rapidly radiating forwards along a linear trajectory to reach the ipsilateral forehead, eye, or nose in a few seconds , may need to be differentiated with LH, as LH is also defined with topographical criteria. NH was first described by Pareja et al. in 2002   is more prone to be activated by cortical spreading depression (CSD) due to the sensitization of meningeal nociceptors caused by immuno-vascular interactions Levy . This reThe current LH cases and those originally described show a clear-cut clinical picture. LH is basically characterized by recurrent or chronic unilateral pain circumscribed in a line-shaped area linking one endpoint in occipital or occipitocervical region with another one endpoint in ipsilateral nose or forehead region, accompanied with or without nausea, vomiting, dizziness and mild temporal pain. So far, anti-migraine therapies have been shown effective in individual patients. This report reinforces the proposal that LH is a new headache syndrome or a new variant of previously known headache syndrome, probably of migraine. Most patients require therapeutic measures. At this stage, no definite explanation can be provided, but the clinical features point to a pathophysiological pathway similar to that of migraine. Further observations and pathophysiological studies are required for a definitive characterization and comprehension of this headache.


P = 27 mW; frequency f1 = 5.8 Hz, f2 – continuous waveform; time T = 1.14 min; dosage of 2 J/cm2 once daily); group 2 (controls) – 90 patients who received pharmacotherapy (Granofurin and solcoseryl given twice daily). The indices we assessed were pain intensity, erythema dynamics and epithelization time. Pain was completely managed in 55.6% of group 1 patients one day after therapy began, while it took three days to alleviate pain for 11.1% of the patients in group 2. The erythema was managed entirely in 24.4% of group 1 patients after the first session, while it did not change in any of the group 2 patients. Pain intensity and erythema had similar dynamics for both groups. In 5 days, 75.6% of group 1 patients showed complete epithelization, while in group 2 the process was completed in only 37.8% of patients. As a whole, the results we obtained using LLLT to treat chronic RAS were better than those obtained in the group receiving pharmacotherapy. Pain and inflammation were very effectively managed with LLLT with the parameters we used and epithelization was considerably accelerated.The aim of this study was to clinically assess the therapeutic effect of low-level laser therapy (LLLT) on chronic recurrent aphthous stomatitis (RAS) using a protocol we developed especially for the purpose. The study included 180 patients: group 1 (the study group) – 90 patients who received LLLT using a laser operating in the red spectrum (658 nm; in a non-contact mode; power output  Chronic recurrent aphthous stomatitis (RAS) is a disorder characterized by small recurrent ulcerations in the oral mucosa. The main symptom of which patients complain is intense pain. The etiology of the condition is unknown, with stress being the main factor presumed responsible for causing it. The ulcers are clearly defined, small round lesions with a red erythematous halo. They appear predominantly on the movable oral mucosa, especially the inner side of the lips and cheeks, tongue and soft palate. They often appear in clusters of two or three lesions. The pain may be so extreme as to interfere with talking and eating.Different therapeutic modalities have been tested for managing the condition. ConvissaThe effects of low-level laser therapy (LLLT) on the trophics and regeneration of the tissues have been convincingly demonstrated experimentally. The biosThe aim of this study was to clinically assess the therapeutic effect of LLLT on RAS using a protocol developed by us especially for the purpose.The study included 180 patients with chronic RAS whom we treated between 2007 and 2012. The distribution of patients by sex was: 17.2% male patients and 82.8% female patients. The mean age of patients was 43.01 ± 1.25 years. Informed consent was obtained from all patients, and the study was approved by the ethical committee at the Medical University of Plovdiv.Group 1 (the study group) consisted of 90 patients who received LLLT in the red spectrum (λ = 658 nm) using a protocol we developed especially for the study.Group 2 (control group) comprised 90 patients receiving conventional pharmacotherapy.The patients were randomly divided into two groups at the beginning of the study.Exclusion criteria for Group 1 were: (1) all forms of leukoplakia and (2) proliferative processes of the oral mucosa.2. The area of irradiation included the aphthous lesion and the mucosa adjacent to it (0.5 to 1 cm in diameter). The characteristics of the laser irradiation were as follows: power output P = 27 mW; frequency f1 = 5.8 Hz, f2 – continuous waveform; time T = 1.14 min; dosage of 2 J/cm2. We conducted a session a day until symptoms abated.The therapeutic protocol for group 1 was as follows: the laser therapy was conducted using a SIX Laser TS diode laser system with an irradiation wavelength of 658 nm. This wavelength was chosen on the basis of reports of positive evidence for its effect. The aphtThe therapeutic protocol for group 2 patients included application of Granofurin and solcoseryl twice daily until symptoms disappeared.The effect of each specific treatment was assessed by gauging the changes in pain intensity, erythema and epithelization time. The assessment was made at 1, 2, 3 and 5 days.Pain: A 10-point visual analogue scale was used to measure pain dynamics, 0 points were scored for no pain; 1 to 5 points, for mild pain and 6 to 10 points, for severe pain.Erythema: The presence, reduction and absence of erythema were recorded.Epithelization: The assessment included absence, beginning and completion of epithelization.The statistical analysis of the results was performed with SPSS v. 17 and MS Office Excel 2003.There were no significant correlations between patients’ sex and age and the studied parameters for all patients and within each group we compared. The group a patient belonged to had a strong inverse correlation with the study variables after treatment began. The results from the statistical analysis are presented in The study variables – pain intensity, erythema and epithelization of the ulcers – had the following dynamics.Prior to therapy all patients in both groups complained of severe pain. Therapy started simultaneously for both groups.The dynamics of the indicator pain for patients in group 1 are shown in The dynamics of the indicator pain for patients in group 2  showed tPrior to therapy, all patients developed erythema around the aphthous lesion. At the beginning of treatment this parameter was identical for both groups.The dynamics of the indicator erythema for patients in group 1  demonstrIn contrast, the dynamics of indicator erythema for patients in group 2  showed nThe dynamics of the indicator epithelization for patients in group 1  did not In group 2, the dynamics of the indicator epithelization  did not Pain, as a major symptom of the disease seriously, affects eating and speech resulting in deterioration of the quality of life. In group 1, pain was managed completely in 55.6% of the patients as early as one day after the beginning of therapy, the patients with no effect of the treatment being only 11.1%. In group 2 there was no patient with completely managed pain, while the patients for whom the conventional therapy gave no effect were 67.7%. At day 3 in group 1, 100% of the patients were pain-free, while the group 2 patients still felt some pain even at day 5  and 2.Erythema developing around the aphthous lesion is a sign of inflammation. The reduction of the size of erythema is a sign of a successful healing process. The RAS in 24.4% of the patients in group 1 was managed successfully after the first procedure, with the remaining cases showing different degrees of successful management of the condition; while in group 2 there were no patients in whom RAS was effectively managed. All group 1 patients at day 3 had their ulcers successfully treated, whereas no patient in group 2 had the condition managed. These results are similar to the ones we obtained in the assessment of pain. The two parameters changed in parallel in both groups.Epithelization is a sign of healing. Epithelization in group 1 was completed five days after beginning of therapy in 75.6% of patients, while in group 2 it was completed in only 37.8% of them.Thus, the results demonstrated indirectly that the disturbed eating and speech in group 1 patients were restored by day 3, while in group 2, by the end of the study (day 5), we observed complete re-epithelization in only a small part of the patients. As a whole, we found LLLT to give better results in the treatment of chronic RAS than conventional pharmacotherapy. The chosen wavelength (658 nm) and LLLT parameters led to very efficient management of pain and inflammation, and to considerable acceleration of the epithelization process. LLLT was shown to exert analgesic, anti-inflammatory and regenerative effects in managing chronic RAS, which is in good agreement with recent developments in LLLT for RAS treatment. Low-level laser can decrease the healing time, pain intensity and also decrease the time of pain relief in patients with aphtae. LLLT alsThe technique we used in managing chronic RAS with LLLT showed greater efficacy than pharmacotherapy. Patients already felt better on the day following the first procedure. The light wavelength we used (658 nm) and the chosen parameters of the laser operation led to very efficient management of the pain and inflammation symptoms. In addition, epithelization was considerably accelerated. The obtained results indicate that low-energy laser therapy applied with this technique is a reliable therapeutic modality to treat chronic (RAS).


Introduction: Coronary artery disease (CAD) is a persistent public health problem worldwide. Chest pain is one of the perceptible symptoms of the same disease. Literature has found acute chest pain as plausible risk factors for CAD. Nevertheless, none of the study has estimated duration from chronic chest pain to the diagnosis of CAD. The objective of the study was to estimate duration from chronic chest pain to CAD and to assess impact of risk factors on same duration.Methods: Data were obtained from community based study on 17,232 Saudi adults. History of patients about onset of chest pain and other risk factors were inquired. Descriptive measures were obtained by Kaplan-Meier curve. Effect of demographic and clinical factors was assessed by Cox regression models.Results: Out of 24% patients with chest pain, 21% diagnosed with CAD. The average duration was 5 years. About 12% of patients with chest pain diagnosed with CAD after one year. Advancing age, female gender, no exercise and reduced high density lipoprotein (HDL) were significantly hazardous predictors throughout duration from chest pain to diagnosis of CAD.Conclusion: The duration from chest pain to CAD was 5 years. Age, gender, exercise and HDL can be variables of concern to deteriorate hazards of CAD for patients with chest pain. Thus, this study filled the gap while estimating duration of diagnosis of CAD for those patients who encountered chest pain in past. Such analysis will help cardiologists to treat patients having chest pain with framed duration. Furthermore, risk assessment analyses assist physicians to focus more on the specified significant risk factors to avoid hazards of encountering CAD. Therefore, another objective of the study was derived to identify hazardous predictors which jeopardize the risk of shortening this time duration.Chest pain is one of the perceptible symptoms of coronary artery disease (CAD).The data were obtained from 5-years National Epidemiological Health Survey on CAD in Saudis. Permission from principal investigator was taken to work on this academic research project. Multi-stage random sampling was conducted in 13 regions of Kingdom of Saudi Arabia (KSA). Urban and rural areas of each region were considered as strata. Thus, out of 1623 primary health care centers (PHCS) in KSA, 58 were randomly selected from urban strata and 66 PHCS were selected from rural strata. Second stage cluster sampling was performed while selecting household from urban and rural community. A ratio of 2:1 was used for selecting the same. Intuitively, 100 households from urban and 50 households from rural community were selected as sampling units. A total of 17232 subjects were sampled by multi-stage random sampling of households and PHCS distributed in urban and rural areas of 13 regions in KSA.Subjects of both genders between 30-70 years of ages were included in this study. A detailed questionnaire was also filled which included questions related to history and current activities of the participants. They were interviewed about their demographic profile and investigation of risk factors associated with CAD was also made. Demographic profile comprised of questions about age, gender, marital status, education status, monthly household income, occupation and housing type. Family history, exercise frequency, smoking status, presence of any other symptoms and number of times of hospital admission were the questions asked for assessing probable risk factors of CAD. Height, weight and other anthropometric measurements were taken for physical examination. Moreover, clinical diagnoses were performed by well-trained physicians. These diagnoses included lipid tests, electrocardiography (ECG), exercise tests, coronary angiography, blood pressures, glucose levels etc.13 Age, gender, body mass index (BMI)14, waist circumference (WC)15, systolic & diastolic blood pressures 16, fasting blood sugar (FBS)17, serum cholesterol (S. Chol.), serum triglycerides (S.TG) and high density lipoprotein (HDL)18 were the prominent associated factors with CAD among Saudi population. This article is the series of earlier publication of the same research on assessing prevalence of CAD and its risk factors.The patients were asked about when they had their first chest pain in past. The number of patients who were diagnosed to have CAD was established in finding of one or more of the following criteria: either physician’s clinical assessment of the chest pain as angina, previous myocardial infarction (MI), or findings of evidence of previous MI by ECG. An article published in this series reported the prevalence of CAD in KSA was approximately 6%.The statistical analyses were conducted using Stata v. 12.0. The data were converted from snapshot  to time dependent. Duration of chest pain was set as time variable. CAD presence in the patients was set as event variable. The patient who had chest pain in past but had not diagnosed with CAD were censored. The patients, who were diagnosed as CAD patients, had not chest pain in past were truncated. Descriptive duration analysis was computed in terms of mean ± standard deviation and median (inter-quartile range). Frequency and percentages were computed for categorical variable. Bivariate association of factors with CAD among patients with chest pain was assessed by Chi-square test. Kaplan-Meier duration analysis was executed to estimate duration of chest pain on different time span. The duration of chest pain was compared in study population who were adhered with different status of significant risk factors. Mann-Whitney U test and Kruskal-Wallis test followed by Tukey’s type non-parametric post-hoc test were employed for the factors with two and at-least three categories respectively. Stratification with the status of CAD presence was also done and two-way non-parametric analysis of variance was run to study effect of risk factors on duration of CAD. To predict the duration of chest pain to CAD in presence of factors and covariates with p value less than 0.20 at univariable analyses, stepwise Cox regression model was run while setting p values of stay and removal as 0.05 and 0.10 respectively. The accuracy of model was checked by Receiver Operating Characteristic (ROC) analysis. Somers’ D coefficient was calculated to assess magnitude of accuracy of the model.st and 3rd quartiles of the same respectively. Kaplan-Meier estimator revealed that 88% of the patients with chest pain did not experience CAD by 1st year (95% CI: 86.5%–89.5%). This endurance reached about half of the above proportion (43%) by 5 years of the duration. All the patients with 17 years of chest pain were diagnosed as CAD patients with duration function of 8.3% (95% CI: 6.6%–10.2%). A similar panorama is suffered by the CAD patients with duration of at least 25 years of chest pain with very low duration function  endured chest pain in past. Cardiac chest pain was experienced by 884 (85.3%) patients out of 1,036 CAD patients. This also reckoned that 21.2% (884/4157) of patients with chest pain experienced coronary artery disease. The shortest duration from chest pain to the diagnosis of CAD was 1 year and the longest was 40 years. The median duration was 5 years with 2 and 10 were 1function .About 24% of the patients with chest pain endured CAD . The proComparing the duration from chest pain in those participants who either suffered CAD or not, the patients with CAD had shorter duration . HyperteCrude and Adjusted hazard ratio obtained by duration model are shown in The area under the receiver operating characteristics curve was 64%  indicati20 These individuals endure noteworthy prevalence of CAD.13 Several studies have been done for studying risk factors of CAD.24 Wilson et al developed predicted score for the risk of coronary heart disease25 which is considered to be generalized score for any cardiac patients.11 The score also predicted first coronary events26 and determined highest risks of coronary events in elderly age of both men and women. Later, prediction scores for coronary disease via logistic model were built for primary care patient with acute chest pain.12 Duration of symptom was considered to be the significant predictors in the model.12 Furthermore, duration of mortality due to CAD was predicted in Australian population.28 Mingala and Estolano made an attempt to estimate duration of hospital stay for patients suffering MI.29 As far as authors’ knowledge is concerned, the time duration from the first onset of chronic chest pain to the true diagnosis of CAD has never been studied yet.The population of KSA includes inhabitants from various countries.30 Current duration survival analysis was introduced by Keiding et al 31 and Ali et al 32. These gaps incited the idea that we exerted an attempt to analyze the duration of CAD from chest pain from a cross sectional sample.For the analysis of duration data, two study designs have been recommended cross sectional or cohort study designs. Though, cohort study requires time to observe complete duration while cross sectional study needs knowledge of duration of disease for the currently enrolled patients.29 The average duration of CAD mortality was varied from 10 years33 to 25 years.34 Combining these outcomes, we can say now that duration from chronic chest pain to the CAD mortality varied from 15.5 years to 30.5 years.The study estimated average duration from chest pain to the diagnosis of CAD as 5 years. Mingala and Estolano reported the average duration of hospitalization for CAD patients was 0.5 years.3 The prevalence of chest pain in Saudi adults is found to be 24% by this study. This prevalence is also relatively high in male and female residing in KSA.Hermingway et al studied prevalence of angina across 31 countries by systematic review. The study reported average weighted prevalence in female was 6.7% while in male, it was 5.7%. In population of Iran, the same prevalence was found to be 4.3%.4 By our study, it was found that 85.3% Saudi population encountered cardiac chest pain leading to CAD. Though, in primary care6, study identified 8.2% of cases as CAD in a cohort with chest pain. A study from United States indicated 83.3% prevalence of CAD among patients with chest pain.35 Similarly, a 300 weeks follow up study5 reported that CAD was prevalent in 12% of the patients with chest pain. This study also advised that great considerations should be made on patients with chest pain as in this study out of 24620 cohort of patients with chest pain, 672 (2.7%) diagnosed with any one of the thoracic ailments.Sarraf-Zadegan et al reported that in Iran cardiac chest pain leading to CAD endured by 19.4% of population.13 Advancing age and gender had also considered as significant risk factors for CAD among Iranian population.36 Exercise was not a significant predictor by regression model in the same study. However, in our study increasing exercise showed significant hazards for CAD for the patients who encountered chest pain. This indicated that patient who encountered chest pain should be vigilant for their exercise habits. These findings can be comparable with another study by Bosner et al. in which age/gender with exercise were the leading predictors for the development of CAD among primary care patients with acute chest pain.10 HDL was the only metabolic syndromes affected the hazards of CAD to the chest pain patients. The accuracy of the model is moderately good and magnitude of accuracy is acceptable. This indicated that stepwise Cox model for studying duration of chest pain is good enough to apply.Amongst the known risk factors for the development of coronary artery disease, this study indicated certain predictors which were hazardous for the chest pain patients concerning the same disease. Increasing age is significantly hazardous during the time span from chest pain to CAD. Though, this effect is slight similar as reported for overall population at risk of CAD in the earlier article.The duration from chest pain to CAD was computed to be 5 years. Age, gender, exercise, and HDL were the significant predictors that best describe the distribution of duration from chest pain to CAD. Physicians should prioritize these factors as variable of concern for the patient with chest pain to avoid risk of having CAD in long haul.Approval of study was obtained from Board of Advanced Study and Research of the institute.Authors declare no conflict of interests in this study.


The aims were to compare somatosensory function at the TMJs and conditioned pain modulation (CPM) effects between TMJ arthralgia and OA patients diagnosed clinically and based on different imaging techniques and age- and gender-matched healthy controls (n = 58) underwent standard clinical examination and three different TMJ imaging modalities. After each examination, they were classified into arthralgia or OA based on the findings. TMJ region somatosensory testing was performed in all participants. Z-scores were calculated for patients based on healthy reference data. CPM was tested by comparing pressure pain thresholds (PPTs) at TMJ and thenar (control) before, during and after the application of painful and nonpainful cold stimuli. Data were analyzed using analyses of variance.Patients (P < 0.048). OA patients showed pressure hyperalgesia compared with arthralgia patients (P = 0.025). There was a significant CPM effect at both test sites during painful cold application in all groups (P < 0.001). There was no significant difference in the relative CPM effect between groups except for clinically diagnosed arthralgia patients showing reduced CPM effect compared with controls (P = 0.047).Somatosensory abnormalities were commonly detected in both patient groups. Assessment of somatosensory function at the TMJ revealed that arthralgia patients were less sensitive to warmth, cold and tactile stimuli than OA patients  contains supplementary material, which is available to authorized users. Temporomandibular disorders (TMD) comprises a heterogenous group of complex disorders having varied and often multifactorial aetiologies , 2. TMD Moreover, due to the diverse nature of TMD symptoms, patient evaluation with clinical examination alone is insufficient to fully assess the osseous and soft tissue components of the TMJ and often requires imaging to strengthen the diagnostic process , 9. AlsoChronic TMJ pain has been associated with somatosensory disturbances such as increased pain sensitivity , 15. SomEndogenous pain modulation, involving supraspinal diffuse noxious inhibitory controls (DNIC), has been shown to be impaired in patients with idiopathic pain disorders such as fibromyalgia, tension type headache, painful osteoarthritis and TMD –27. The Therefore, the aims of this study were (1) to compare the somatosensory function at and around the TMJ in TMJ arthralgia and OA patients diagnosed clinically without and in combination with different imaging techniques and (2) to examine whether the CPM differs between the TMJ arthralgia and OA patients diagnosed clinically without and in combination with different imaging modalities and also in comparison with healthy controls.Fifty-eight TMD pain patients  and 41 age- and gender-matched healthy participants  were included. The patients were recruited from the Section of Orofacial Pain and Jaw Function, Department of Dentistry, Aarhus University. The healthy participants were invited to participate in the study by posting advertisement on web pages and flyers at and around the university regarding the study. The study was conducted at the Institute of Odontology and Oral Health and the imaging techniques such as MRI and high-resolution ultrasonography (HR-US) were performed at Aarhus University Hospital. Prior to the study, all the participants were clinically examined according to the RDC/TMD axis I protocol  = 43.1 %), this frequency is actually lower than would be expected [A few somatosensory deviations, ie, Z-scores oustside the 95 % CI, were also detected in the healthy reference group. A total of 31.7 % of healthy controls showed one or more values outside the 95 % CI. However, based on the simple calculation of chance probability of being healthy and having at least 1 of the 11 values outside the 95 % CI  when compared with arthralgia patients, whereas arthralgia patients demonstrated a higher frequency of negative somatosensory signs compared with OA patients. Hyperalgesia was documented in OA, where patients showed increased sensitivity to blunt pressure at both test and control sites compared with arthralgia patients and also OA patients diagnosed on combined examinations showed hyperalgesia to heat pain and punctuate stimuli compared with controls but not in comparison with so-called pure arthralgia patients. Hyperalgesia to pressure pain, pinprick stimuli and heat pain has also been shown in patients with OA of other joints like knee and hand , 67. It Impairment of the endogenous analgesic systems has been implicated as a contributing factor in the development and maintenance of many chronic pain conditions including TMD . HoweverThe assessment of sensory and pain thresholds using a standardized QST protocol uncovered an array of somatosensory abnormalities in both TMJ arthralgia and OA patients diagnosed clinically and based on different imaging modalities. Profiles of somatosensory function were able to differentiate between these conditions. TMJ OA patients demonstrated more pronounced hyperalgesia compared with arthralgia patients suggestive of central as well as peripheral sensitization. In contrast, arthralgia patients were mostly associated with somatosensory loss of function to non-nociceptive parameters compared with OA patients. Thus, our study points towards involvement of different underlying pain mechanisms in different TMJ pain conditions, which may have significant impact on diagnosis and rational management of these disorders. The CPM effects were similar in both patient groups and healthy controls, implying that chronic painful TMJ may not be associated with dysfunctional endogenous analgesic systems. Now, it remains to be tested if subgroups of TMD pain patients with different underlying pain mechanisms respond to different therapeutic approaches.Additional file 1:Supplementary material (DOCX 37 kb)Additional file 2:Supplementary Tables (DOCX 26 kb)Additional file 3:Supplementary Figures (PPTX 2246 kb)


Purpose. To evaluate the analgesic efficacy of 0.5% propacaine hydrochloride as topical anesthesia during phacoemulsification surgery.  Methods. Intraoperative pain intensity was assessed using a 5-category verbal rating scale during each of three surgical stages. Pain scores from each surgical stage and total pain scores were compared for the factors of patient age, gender, cataract laterality, and type. Results. In comparison of cataract type subgroups, the mean total pain scores and mean stage 2 pain scores in both white mature cataract (WMC) and corticonuclear plus posterior subcapsular cataract (CN + PSC) groups were significantly higher than in the PSC-only (PSC) group (P < 0.05). Conclusion. Phacoemulsification with topical anesthesia is not a completely painless procedure. Pain intensity varies with cataract type and stage of surgery. For routine cataract surgery, topical anesthesia is preferred because it provides sufficient patient comfort with lower incidence of complications compared to other types of anesthesia , 2.The three most common methods of applying topical anesthesia are by eye drops, by eye drops with intracameral lidocaine injection, and in gel form , 4. TopiThis study aimed to determine the efficacy of topical anesthesia by 0.5% propacaine hydrochloride in controlling pain and providing intraoperative comfort for patients undergoing phacoemulsification.This prospective study included 63 eyes from 63 patients who presented at the Erzurum Regional Training and Research Hospital between March 1st, 2011, and October 1st, 2012. These patients had no medical history of ocular surgeries or pathologies such as glaucoma, traumatic cataract, or high myopia.The pain scoring system was based on the Keele verbal pain chart  Table 1Table 1. Patients were grouped according to age, gender, laterality, and cataract type. The pain score for each surgical stage and total pain score were compared between groups. There were three age groups: 40–59, 60–75, and 76–97 years old. The three categories of cataract were white mature cataract (WMC), posterior subcapsular cataract (PSC), and corticonuclear plus posterior subcapsular cataract (CN + PSC).The American Optometric Association's grading system for cataracts  was usedNone of the patients received sedation prior to surgery, and each patient underwent the same three-stage procedure performed by a single surgeon . PatientDuring the procedure, care was taken to avoid conjunctival manipulation.Immediately after the operation, the eye was closed and the patient was moved to the inpatient clinic. In the clinic, patients were interviewed using the questionnaire below. They were asked to rate the success of their procedure and explain why they answered as they did.I think my surgery went well, because...I don't think my surgery went well, because...(c)I don't have an opinion about whether my surgery went well or not.How do you think your surgery went? Why do you think this way?P < 0.05.The pain score data were analyzed statistically using SPSS 17.0 software. The variables were compared using Kruskal-Wallis, Mann-Whitney, and chi-square tests. Differences were considered significant at The study was approved by the Regional Committee for Medical Research Ethics of Erzurum Training and Research Hospital, Turkey.n = 21; PSC, n = 20; CN + PSC, n = 22. The laterality distribution was 28 right eyes (44.4%) and 35 left eyes (55.5%). The procedures were performed without any complications.The 63 patients had an average age of 69.27 ± 12.91 years (range: 40–97 years). The age distribution of the patients was as follows: 17 patients between 40 and 59 years; 25 patients between 60 and 75 years; 21 patients between 76 and 97 years. There were 32 men (50.7%) and 31 women (49.2%). The cataract type distribution was as follows: WMC, During surgery, 56 patients (88.9%) received only topical anesthetic drops, whereas 7 patients (11.1%) described severe or unbearable pain and received additional intracameral lidocaine injections . Of the n = 3; CN + PSC, n = 3). The analysis revealed that all patients in the WMC group experienced pain in one or more stages of the surgery.When the pain scores from all surgical stages of all 63 patients were analyzed, 6 patients (10.5%) experienced no pain throughout the entire procedure .In patients who received only topical anesthesia, the average total pain score was 3.05 ± 1.24 (0–5); the average for stage 1 was 0.75 ± 0.43 (0-1), for stage 2 was 1.27 ± 0.67 (0–2), and for stage 3 was 1.04 ± 0.5 (0–2). Kruskal-Wallis nonparametric test was used to analyze the relation between cataract type and both mean total pain score and mean pain score per stage    who felt no pain during the procedure, three in each of the PSC and CN + PSC groups; all of the patients in the WMC group experienced some level of pain.Of the 63 patients who completed the postoperative questionnaire, 48 patients (76.1%) believed that their procedure had been successful, 5 patients (7.9%) believed that it had been unsuccessful, and 10 patients (15.8%) had no opinion. Of the 48 patients who considered their procedure successful, 33 patients (75%) gave different explanations for their opinion, but 15 patients (23.8%) gave similar answers. These 15 patients belonged to the WMC group, and it became apparent that their perception of surgical success was based on the fact that they experienced an immediate visual improvement when the white mature cataract was removed. All five patients who believed that their procedure was unsuccessful had received a lidocaine injection; the reason that they felt their surgery had been unsuccessful was based on the pain that they experienced during the procedure (three in the CN + PSC group and one in each of the PSC and WMC groups).Clear corneal phacoemulsification surgery has been the subject of many studies –11. The In this prospective randomized study, we evaluated the effects of cataract type, age, gender, and laterality on the efficacy of topical 0.5% propacaine hydrochloride anesthesia in providing patient comfort during phacoemulsification.Soliman et al. reported that 73.3% of patients that received topical 0.4% benoxinate and 10% of patients that received topical 0.5% bupivacaine during phacoemulsification surgery had severe to unbearable pain which led to addition of subtenon lidocaine injection [P < 0.05). This was thought to be referred pain caused by mechanical effects of nucleus rotation or intracapsular manipulation on surrounding tissue, especially the corpus ciliare region, which were necessary due to the high density of the cataracts.Analysis of the data from 56 patients who received only topical anesthetic drops revealed that the mean total pain scores and mean stage 2 pain scores in both WMC and CN + PSC groups were significantly higher than in the PSC group  during phacoemulsification was investigated. They reported that the mean verbal pain score of 80 patients in the oral placebo group was 1.11 ± 0.73 . In our The analysis of the questionnaire showed that 15 patients considered their procedure successful because their visual clarity improved during surgery upon cataract removal. It is noteworthy to mention that all of these patients were from the WMC group. WMC blocks more light compared to other types of cataract; therefore, phacofragmentation of the cataract during surgery significantly changes the patients' perception of the brightness of the microscope lamp. This change may have led the patients to conclude that their surgery was successful. Another point of note is that the five patients that required additional lidocaine injection all considered their procedure unsuccessful due to feeling severe or unbearable pain during their surgery.In conclusion, phacoemulsification with topical anesthetic eye drops is not a completely painless procedure. The majority of patients feel mild or moderate pain, and patients with dense cataracts are more likely to experience severe to unbearable levels of pain. Our data suggest that intense pain leads patients to believe that their procedure was unsuccessful, whereas immediate visual improvements during surgery lead to a belief that the procedure was successful. Therefore, patients need to be informed preoperatively that their visual clarity or pain sensations do not reflect the success of the procedure.


Introduction. In this study, we elucidate the possible causative role of chronic subclinical inflammation in jawbone of patients with atypical facial pain (AFP) and trigeminal neuralgia (TRN) in the local overexpression of the chemokine regulated on activation and normal T-cell expressed and secreted (RANTES/C-C motif ligand 5 CCL5). Neurons contain opioid receptors that transmit antipain reactions in the peripheral and central nervous system. Proinflammatory chemokines like RANTES/CCL5 desensitize μ-opioid receptors in the periphery sensory neurons and it has been suggested that RANTES modifies the nociceptive reaction. Materials and Methods. In 15 patients with AFP/TRN, we examined fatty degenerated jawbone (FDOJ) samples for the expression of seven cytokines by multiplex analysis and compared these results with healthy jawbones. Results. Each of these medullary jawbone samples exhibited RANTES as the only highly overexpressed cytokine. The FDOJ cohort with AFP/TRN showed a mean 30-fold overexpression of RANTES compared to healthy jawbones. Conclusions. To the best of our knowledge, no other research has identified RANTES overexpression in silent inflamed jawbones as a possible cause for AFP/TRN. Thus, we hypothesize that the surgical clearing of FDOJ might diminish RANTES signaling pathways in neurons and contribute to resolving chronic neurological pain in AFP/TRN patients. All samples showed the clear presence of fatty-degenerative osteonecrosis spreading up to several centimeters in the form of retromolar cavities in the cancellous bone. This brought Bouquot to propose the term “Neuralgia-Inducing Cavitational Osteonecrosis (NICO)” to describe the clinical phenomenon of neuralgia in conjunction with fatty-degenerative osteolysis and osteonecrosis of the jawbone (FDOJ) [The etiology of chronic facial pain is challenging to diagnose and difficult or frustrating to treat. Many different concepts have been presented and discussed, for example, the presence of a neuroma, implying that the nerve has been damaged in the periphery, and intracranial vascular compression of the trigeminal nerve root at the base of the skull. In 1997, Jannetta published a long-term follow-up study of the surgical approach to move the superior cerebellar artery away from the nerve root, maintaining the artery in its new position with a suture . Chronice (FDOJ) . Furthere (FDOJ) . NotwithThis study was performed as a randomized controlled trial. We collected FDOJ tissue samples from 15 patients with AFP/TRN. A diagnosis of AFP/TRN was made by neurologists, pain specialists, and physicians. Inclusion criteria were (1) therapy-resistant pain that was clinically similar to AFP/TNR and (2) the local diagnosis of FDOJ in the painful jaw site. Mandatory inclusion criteria were (3) the availability of two-dimensional orthopantomograms (2D-OPG) and (4) cone beam three-dimensional  images. A further inclusion criterion for the group with surgery in the AFP/TRN areas was the measurement of bone density of the jawbone with transalveolar ultrasound technology (TAU). Besides 2D-OPG and 3D-DVT, the definite indication for FDOJ surgery was the additional measurement of bone density by TAU. TAU is a useful tool for establishing FDOJ –13. PatiThe softening in FDOJ bone marrow is so distinct that the marrow space can be sucked and spooned out. Hollow cavitations with fatty degenerated adipocytes have undergone dystrophic changes accompanied by demyelination of the bony sheath of the infra-alveolar nerve. All 15 FDOJ samples presented clinically and macroscopically as fatty lumps. FDOJ is similar to silent inflammation or subclinical inflammation without the typical signs of acute inflammation. The current treatment of FDOJ lesions consists of curettage of the bony cavity, which relieves symptoms of pain with varying rates of success , 14, 15.μL of cold protease inhibitor buffer . The homogenate was then centrifuged for 15 minutes at 13,400 rpm. Next, the supernatant was collected and centrifuged for further 25 minutes at 13,400 rpm. In the 15 supernatants of tissue homogenate, we measured, regulated on activation, normal T-cell expressed and secreted (RANTES), also known as chemokine C-C motif ligand 5 (CCL5), FGF-2, interleukin- (IL-) 1 receptor antagonist (ra), IL-6, IL-8, monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNF-α). Measurement was performed using the Human Cytokine/Chemokine Panel I  according to the manufacturer's instructions and analyzed using Luminex 200 with xPonent software .In the examining Institute for Medical Diagnostics, Nicolaistrasse 22, 12247 Berlin inspected by DAKKS , the samples were homogenized by mechanical force in 200 Parallel to the cytokine analysis, each FDOJ sample was examined histopathologically .n = 15) are shown in As we showed in earlier publications , 16, then = 13), necrotic adipocytes (n = 10), myxoid degeneration (n = 12), and increased fat cells (n = 12); inflammatory cells were only found in one FDOJ sample. In the pathohistological findings the amount of fat cells was consistently and strikingly increased in FDOJ samples. Typical signs of inflammation, especially of an inflammatory cell response, were absent. The fatty-degenerative and osteolytic aspects occurred due to insufficient metabolic supply in an ischemic state. The histologic examination of the curetted tissue demonstrated ischemia  . The resSince spring 2009 I had been getting recurring stabbing pain on the left-hand side of my face and earache, tinnitus and pain in my shoulder/arm. During the night I suffered palpitations and panic attacks. My physical energy levels also dropped. I consulted a further two dentists to no avail. One recommended that I went to see a neurologist, who prescribed me strong painkillers and psychotropic drugs. A trip to an osteopath was also unfortunately fruitless. In summer 2011 I was in a horrendous amount of pain, particularly at night. I could barely sleep through the night. I was taking strong painkillers every day just to get me to work. Then came the day when everything was solved. On 15 February 2012 I had an operation on the left side of my upper jaw and bone was excavated. After about 4 weeks I was almost pain-free without medication.”To show the extent to which curettage of FDOJ in patients affected by AFP/TRN can contribute to alleviating facial pain and to give an example of the clinical relevance of FDOJ, our patient Mrs. N. T. reported the following: “Although the role of proinflammatory cytokines and chemokines has been identified in neuropathic pain , the exa