Postoperative mobidity following third molar surgery is affected by a number of factors. The study of these factors is essential for effective planning and limitation of morbidity. The aim of this study was to determine the effect of age, type of impaction and operative time on immediate postoperative tissue reactions following mandibular third molar surgery.Consecutive patients with impacted mandibular third molar teeth were studied. All the third molars were classified according to Winter's classification. Surgical extraction was performed on all the patients by a single surgeon under local anaesthesia. The operation time was determined by the time lapse between incision and completion of suturing. Postoperative pain, swelling and trismus were evaluated.There were 120 patients with an age range of 19-42 years. Patients in the age range of 35-42 years recorded a lower pain score (p = 0.5) on day 1. The mouth opening was much better in the lower age group on day 2 and 5 (p = 0.007 and p = 0.01 respectively). Pain, swelling and trismus increased with increasing operative time. Distoangular impaction was significantly associated with higher VAS score on day 1 and 2 . Distoangular and horizontal impaction are associated with a higher degree of swelling and reduced mouth opening on postoperative review days. Vertical impaction was associated with the least degree of facial swelling and best mouth opening.Increasing operating time and advancing age are associated with more postoperative morbidity, likewise distoangular and horizontal impaction types. The quality of life experienced by patients following third molar surgery is increasingly becoming a health concern . Third mFactors affecting postoperative morbidity could be patient factors, tooth related factors and operative factors . PatientThe surrounding bone in young patients is relatively soft and more resilient compared to older patients, where the bone is harder, necessitating more bone removal, with more difficulty in separating tooth from bone, resulting in more postoperative pain, swelling and trismus ,14. BrucConsecutive patients scheduled to undergo surgical removal of impacted mandibular third molars in the Maxillofacial Surgery Unit of State House Medical Centre, Abuja, Nigeria from February to November 2009, were recruited into the study. Clearance was obtained from the Ethics and Privileges Committee of the hospital and informed consent was signed by the patients before enrolment. Smokers, patient with systemic diseases and patients with active pericoronal lesions were excluded from the study. Orthopantomographic images were used to classify all the impacted mandibular third molars into Mesioangular, Distoangular, Vertical and Horizontal impactions based on Winter's classification.Surgical extraction of a tooth per session was performed on all the patients by the same surgeon under local anaesthesia. For the patients that required bilateral extraction, a gap of at least 15 days was allowed between the two procedures to allow for total recovery from the first one. Access was gained through a 3-sided mucoperiosteal flap and ostectomy was carried out with a fissure bur and normal saline irrigation. With adequate ostectomy, elevation of the tooth was carried out and was followed by socket toileting. Sectioning of the tooth was carried out whenever necessary. They were then discharged home with standard postoperative instructions.The operation time was determined by the time lapse between incision and completion of suturing. They were all placed on broad spectrum antibiotics and analgesics of diclofenac Potassium (cataflam Novartis) 50 mg 8 hourly for 3 days.Postoperative pain, swelling and trismus were evaluated. Pain was estimated subjectively by asking the patient to rate the nociceptive experience on a visual analog scale of 0 to 5. The leaflets were handed over to them for daily entry with day 1 being the operation day and the assessment was done for 7 days.Swelling was assessed by a modification of a 3 line measurements Figure  using 5 Maximum inter-incisal distance was used as the index of trismus using Boyle's gauge-a venier calibrated calliper. Percentage mouth opening was calculated on each postoperative review days. The measurement of MID was taken from the incisal edge of the upper right central incisor  to the incisal edge of the lower right central incisor. Three readings were taken for each patient and the average was determined. This constitutes the reading for the particular day. Baseline measurements were taken just before the surgery and similar readings were carried out on days 2(48 hours), 5 and 7 postoperatively. Percentage mouth opening was calculated thus: postoperative minus preoperative measurement multiplied by 100.Data analysis was carried out with Statistical Package for Social Sciences (SPSS) 15.0 for Windows. A multivariate analysis of the effect of patients' age, sex, type of impaction and operative time on pain, swelling and trismus was also carried out. Mean values are presented with 95% confidence interval.A total of 120 patients comprising 42 male and 78 females were studied.The age range of the patients was 19 to 42 years with a mean (SD) age of 26.7 years. Fifty-eight (48.3%) patients were in the age range of 19-26 years, fifty-three (44.2%) were in the age range of 27-34 years and nine (7.5%) were in the age range of 35-42 years. The effect of age on pain, swelling and trismus is shown in Figure The mean (SD) duration of operation was 22.63 (7.4) minutes with a range of 11 to 35 minutes. The distribution of operative time and its effect on postoperative pain, swelling and trismus is shown in tables The distribution of types of impaction and its effect on pain, swelling and trismus is shown in tables A multivariate analysis of the effect of patients'age, sex, type of impaction and operative time on pain, swelling and trismus is shown in table Severity of pain, amount of swelling and degree of trismus are the primary indicators of patients discomfort following surgical extraction of an impacted third molar tooth .This study recorded a significant influence of age on post operative morbidity following surgical extraction of impacted third molar teeth. A higher degree of trismus and facial swelling was recorded in patients with advancing age. This finding is in agreement with some studies ,18,19. BThis study recorded a lower score of pain perception in the older patient than the younger ones within the first 24 hours of surgery. Pain following third molar surgery has been shown to peak within 24 hours of surgery which has equally been confirmed with this study . InformaThe mean operation time of 22.63 recorded in this study is similar to 21.92 and 25.0 mins reported by Raprastikul et al  and SaglThe commonest type of impaction, mesioangular , recorded in this study is similar to the reports from earlier studies -28. DuriThe knowledge of the effect age, operation time and type of impaction on postoperative inflammatory reactions following third molar surgery is very important because it will assist in treatment planning. It could be used as an objective tool to educate patients on the need for early extraction of an impacted third molar to minimize postoperative morbidity. The type of impaction is developmental and cannot be controlled but the knowledge could assist in objective education of patients on possible postoperative reactions for medico- legal reasons.The authors declare that they have no competing interests.SAB conceived of the study on third molar surgery, participated in its design and coordination and helped to draft the manuscript. EVO and AAA made substantial contributions to the design, acquisition of data and manuscript drafting. WLA and BOB participated in data analysis, interpretation and critical review of intellectual content. All authors read and approved the final manuscript.Seidu Adebayo Bello, BDS, FMCDS, FWACS,Wasiu Lanre Adeyemo, BDS, FMCDS, FWACS, Dr. Med. Dent., FICSBabatunde Olamide Bamgbose, BDS, FMCDSEmeka Vitalis Obi, BDSAdemola A Adeyinka BDS


The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis.This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control . The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs).A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control ; an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was −0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%).This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee.NCT01839331ClinicalTrials.gov  Osteoarthritis (OA) is the most common form of arthritis affecting a conservatively estimated 27 million Americans in 2008 Current drug treatment for OA of the knee relies on pain control with analgesics, anti-inflammatory treatment with non-steroidal anti-inflammatory drugs (NSAIDs), intra-articular (IA) corticosteroids, and IA hyaluronan products. The only evidence based treatment recommendations by the American Academy of Orthopaedic Surgeons (AAOS) for pain due to OA are self-management/physical activity, weight loss, and NSAIDs or Tramadol; patients with pain that is not controlled by these recommended treatments rely on non-recommended alternatives, or eventually knee replacement Human Serum Albumin (HSA) has been commercially approved and in use for over 30 years. It has been safely administered intravenously to humans worldwide and has an excellent safety profile. In common clinical use, HSA is administered as a 5% solution in volumes of 100–500 mL per day in treatment for shock, burns, and plasma volume expansion The Low Molecular Weight Fraction of 5% HSA (LMWF-5A) has not previously been used for the indication of OA. The low molecular weight fraction  of pharmaceutical HSA contains aspartyl-alanyl diketopiperazine (DA-DKP), which is formed after the dipeptide aspartate-alanine is cleaved from the N-terminus of albumin and cyclizes into a diketopiperazine LMWF-5A is being developed to provide relief for the pain of moderate to severe OA of the knee. A previous randomized, placebo-controlled, double-blind study conducted in 43 adults in Australia demonstrated that a single 4 mL IA injection of LMWF-5A is considered safe and well tolerated, and is efficacious at reducing pain in adults with OA of the knee (unpublished).The purpose of this study was to investigate the safety and efficacy of two doses of a single IA knee injection of LMWF-5A on joint pain in OA of the knee. The primary trial objective was to evaluate the greater efficacy of 10 mL LMWF-5A versus 10 mL vehicle control than 4 mL LMWF-5A versus 4 mL vehicle control IA injection in improving knee pain, when applied to patients suffering from OA of the knee. The secondary trial objectives included: the safety of an IA injection of LMWF-5A, and the efficacy of an IA of LMWF-5A on stiffness, function, and overall disease severity.The study was performed in accordance with the principles of good clinical practice guidelines and received institutional review board (IRB) approval from the SUNY-Buffalo Health Sciences IRB and Liberty IRB; written informed consent was obtained from all participants involved in the study. Registration on ClinicalTrials.gov was initiated on March 25, 2013 and preceded patient recruitment (Identifier: NCT01839331).We conducted a randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the effect of two doses of a single IA knee injection of LMWF-5A in patients with symptomatic knee OA. The study was conducted at nine clinics across the United States, and consisted of a 28 day screening period and a 12 week participation period. Patients were enrolled and received treatment between March 29, 2013 and May 1, 2013, with follow-up through July 17, 2013.Patients were recruited from the population being seen by Investigators at the clinics participating in the study. In addition, we recruited patients through notifications sent to referring physicians as well as radio and web-based campaigns.Eligible patients were between the ages of 40 to 85 years old, fully ambulatory, with symptomatic index knee OA of at least 6 months preceding screening and a clinical diagnosis of OA supported by recent radiologic evidence within 6 months of screening, with moderate-to-severe OA pain in the index knee (baseline pain rating of ≥ 1.5 on the Western Ontario and McMaster Universities Arthritis Index (WOMAC®) osteoarthritis Index 3.1 5-point Likert pain subscale Exclusion criteria included: A history of allergic reactions to albumin and its excipients; any human albumin treatment in the 3 months before randomization; concurrent arthritic conditions such as inflammatory or crystal arthropathies, previous major injury, and any other disease or condition interfering with the free use and evaluation of the index knee for the duration of the trial; any pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to randomization; use of the following medications during the study: IA-injected pain medication or topical treatment in the index knee, analgesics containing opioids, significant anticoagulant therapy, immunosuppressants, systemic treatments, or corticosteroids > 10 mg prednisolone equivalent per day.If both knees were osteoarthritic, then at screening the investigator selected the knee that best satisfied the requirements for the study. In cases where both knees satisfied all inclusion and exclusion criteria, the study knee was selected based on greater baseline WOMAC A pain score. Patients were assigned to treatment by a sequential  randomization schedule in blocks of 4 following confirmation of eligibility before study medication was administered as a single intra-articular injection into the knee joint space . Randomization was developed and maintained by an independent statistician. Treatments were provided in kits containing blinded study vials, syringes, needles and acetaminophen (rescue medication). The Sponsor, the investigator, and all study staff having a role in the day-to-day conduct of the study remained blinded to treatment.A total of 329 patients with OA knee pain were randomized 1∶1∶1∶1 across 4 study arms: 4 mL LMWF-5A, 4 mL saline vehicle control, 10 mL LMWF-5A or 10 mL saline vehicle control.The starting material of LMWF-5A, HSA purchased from OctaPharma , was subjected to centrifugation/ultrafiltration under sterile conditions and the ultrafiltrate, containing species with a MW less than 5000 Da, was separated. The ultrafiltrate contained DA-DKP (approximately 50 – 200 µM) and the excipients (i.e. sodium caprylate and sodium acetyltryptophanate). The ultrafiltrate was transferred for aseptic filling, to afford sterile drug product. The control arm in this study was saline vehicle control, rather than a true ‘placebo’, as saline has been shown to induce significant pain relief, especially in trials involving intra-articular injections The clinical effects of treatment on OA were evaluated during clinic visits at 6 and 12 weeks and telephone contacts at 2, 4, 8 and 10 weeks, using the WOMAC® osteoarthritis Index 3.1 5-point Likert score, the Patient's Global Assessment of disease severity (PGA) using a 5-point Likert Score, and the amount of acetaminophen after intra-articular injection. Acetaminophen was supplied in 500 mg tablets at baseline as a rescue medication, and allowed as 1 tablet every 4 hours as needed.Safety was evaluated by recording adverse events , vital signs and physical examination results .The primary endpoint was the change in the WOMAC average pain subscore by 5-point Likert scale between baseline and week 12. Both the Likert and VAS scales are validatedSecondary endpoints included: the incidence and severity of AEs; change in the WOMAC average subscore by 5-point Likert scale for stiffness (WOMAC B subscore), physical function (WOMAC C subscore), and pain with movement and pain at rest ; change in PGA; use of rescue analgesia (acetaminophen).We estimated the sample size based on the mean difference in the WOMAC A pain change from baseline at week 12 using a 2-way ANOVA. The estimate was based on detecting a treatment difference of 1.0 and 0.5 for 10 ml and 4 ml volumes, respectively (with a common SD of 0.9) using a 2 tailed alpha of 0.05. We estimated a sample size of 80 patients into each study arm for a total of 320 patients in a 1∶1∶1∶1 ratio across all 4 study arms  in order to achieve power of at least 80% to demonstrate both main effects  or an interaction between the two main effects.The primary endpoint, change in WOMAC A Pain subscore between baseline and week 12, was analysed using analysis of covariance (ANCOVA) to test the main effects of LMWF-5A vs vehicle control and 4 mL vs 10 mL, and their interaction. The WOMAC A baseline measure was used as the covariate; clinical site effect was non-significant, and therefore was not included (p = 0.42). Residuals of the model were assessed for normalcy and heteroscedasticity to ensure that the model was appropriate.The following secondary endpoints were evaluated between treatment groups using a mixed-effects repeated measures ANCOVA, adjusted for the respective baseline value: change in WOMAC B stiffness, WOMAC C physical function, WOMAC A pain at rest, WOMAC A pain with movement, and PGA. The mixed-effects repeated measures ANCOVA covariance structure was modelled as first-order autoregressive with subject as a repeated effect, and treatment arm and time included in the model; the interaction between treatment arm and time was removed if not significant. Amount of rescue medication  followed a non-normal distribution and was analysed using a Wilcoxon rank-sum test; the study-wide mean pill count was used for imputation of missing data in 29 patients.Adverse events were examined in all patients who were randomized and received study medication; no safety data was imputed. All efficacy analyses were performed in the intent-to-treat (ITT) population, defined as all patients who were randomized, received study medication and had at least one post-baseline observation. The ITT population was analyzed as randomized; data were imputed using a last observation carried forward approach (4.9% of missing data were imputed). The primary endpoint was also examined in subgroups according to Kellgren Lawrence Grade, and prior IA knee injection for pain due to OA.a priori and performed in accordance with the study Protocol and the Statistical Analysis Plan. The protocol and Statistical Analysis Plan for this trial and supporting CONSORT checklist are available as supporting information; see p value < 0.05 for all analyses.Statistical analyses were performed using SAS® software, version 9.1.3 or later . All analyses were defined Patient disposition can be seen in Baseline data is shown in LMWF-5A resulted in a statistically significant improvement in pain as compared to vehicle control , Patients treated with LMWF-5A demonstrated significant improvements in the following secondary endpoints, as compared to vehicle control: PGA , physical function, ; pain at rest ; pain with movement , The effect of LMWF-5A was most pronounced in patients with severe knee OA . In partPatients with prior knee injection observed a significant improvement in mean pain with LMWF-5A as compared to vehicle control at week 12, while patients without prior knee injection saw a borderline significant improvement in pain with LMWF-5A as compared to vehicle control at week 12 .Adverse events were reported for 144 patients (44%), and were similar in patients who received LMWF-5A (41%) and vehicle control (47%), The percent of patients reporting treatment-related AEs was 10% with LMWF-5A and 13% with vehicle control; the most commonly occurring treatment-related AE was arthralgia (n = 17) and injection site pain (n = 7).This randomized clinical trial demonstrated that a single intra-articular injection of LMWF-5A is safe and effective at both 4 mL and 10 mL volumes. Our study represents a potential major breakthrough in identifying a treatment for pain due to moderate to severe OA. Our trial's primary and secondary efficacy endpoints of improvements in pain, function, and overall assessment of disease severity support significant efficacy of LMWF-5A. The clinically and statistically significant reduction in study outcomes with LMWF-5A was observed after only a single IA injection into the knee. Both treatments were well tolerated, with a low incidence of treatment-related adverse events.in vitro and in vivo for its contents and its anti-inflammatory properties. One of the active ingredients, DA-DKP, has been shown to have multiple anti-inflammatory and immune modulating effects This is the first published study to evaluate an intra-articular injection of the low molecular weight fraction of HSA (LMWF-5A) to patients with OA. This low molecular weight fraction of HSA has been extensively evaluated Intra-articular corticosteroids have been used historically for the treatment of OA, but they are believed to be associated with significant safety Despite recommendations against their use, Hylan G-F 20 is the current treatment of choice in patients who cannot be managed with analgesics. In the pivotal trial of a single IA injection of 6 ml Hylan G-F 20, a borderline statistically significant reduction in pain was demonstrated, with an estimated difference from control of −0.15 (95% CI: −0.30 to −0.002), p = 0.047), corresponding to a 31.3% improvement in pain over 26 weeks in patients treated with Hylan G-F20. In comparison, our study demonstrated that a single IA injection of LMWF-5A resulted in a clinically and statistically significant reduction in pain, with an estimated difference from control at the study endpoint of −0.25 (95% CI: −0.41 to −0.08), p = 0.004, corresponding to a 42.3% improvement in pain at 12 weeks in patients treated with LMWF-5A. The accepted threshold for a minimum clinically important improvement (MCII), defined as the smallest change in a measurement that signifies important improvement in a patient's symptom, is −40.8% in WOMAC A pain change from baseline with knee OA, which only LMWF-5A exceeded Our results were even more robust in patients with severe OA (Kellgren-Lawrence Grade IV), with a non-significant treatment effect in patients with minimal OA (Kellgren-Lawrence Grade II), a finding worth discussing. The severity of disease (i.e. pathology at presentation) appeared to result in differing treatment effects in our study. We believe our results are partially due to a pronounced saline effect in patients with minimal OA (Grade II), resulting in a non-significant reduction in pain for patients treated with LMWF-5A over saline placebo in this subgroup. The effect of saline was less pronounced in patients with moderate-to-severe OA, resulting in a clinically and statistically significant reduction in pain with LMWF-5A over saline. We believe LMWF-5A represents an alternative IA treatment, providing relief for the pain of moderate to severe OA of the knee, particularly in patients with severe OA in whom there are currently no pharmacologic treatments.The primary limitation is that our study was designed to follow patients to 12 weeks following IA injection, which may not capture the maximum difference between groups. Systematic reviews of intra-articular injections suggest that the primary endpoint of change in pain is generally measured at 13–26 weeks for IA hyaluronan products In conclusion, this randomized, controlled clinical trial demonstrated that a single intra-articular injection of LMWF-5A is a safe and effective treatment for osteoarthritis. Our results demonstrate improvements in pain and function, as well as overall disease severity with LMWF-5A as compared to vehicle control. These findings represent a potential major breakthrough in identifying a treatment for pain due to osteoarthritis, particularly in patients with severe osteoarthritis where no other safe and effective therapies exists prior to joint replacement.Protocol S1Protocol AP-003A .(PDF)Click here for additional data file.SAP S1Statistical Analysis Plan AP-003-A .(PDF)Click here for additional data file.Checklist S1CONSORT 2010 checklist of information to include when reporting a randomised trial.(DOC)Click here for additional data file.Issued Patents S1Issued Patents for “AMPION”, as of December 5, 2013.(DOCX)Click here for additional data file.


Stress induced by the events of daily life is considered a major factor in pathogenesis of primary tension-type headache. Little is known about the impact that could have a more stressful event, like a natural disaster, both in patients with chronic headache, both in people that do not had headache previously. The aim of the present study was to observe the prevalence of headache in the population following the devastating earthquake that affected the province of L’Aquila on April 6, 2009. The study population was conducted in four tent cities . Sanitary access is recorded in the registers of medical triage, in the first 5 weeks, after the April 6, 2009. The prevalence of primary headache presentation was 5.53% (95% CI 4.2–7.1), secondary headache was 2.82% (95% CI 1.9–4.9). Pain intensity, assessed by Numerical Rating Scale score showed a mean value of 7 ± 1.1 (range 4–10). The drugs most used were the NSAIDs (46%) and paracetamol (36%), for impossibility of finding causal drugs. This study shows how more stressful events not only have an important role in determining acute exacerbation of chronic headache, but probably also play a pathogenic role in the emergence of primary headache. Also underlines the lack of diagnostic guidelines or operating protocols to early identify and treat headache in the emergency settings. Headache accounts for about 1.2–4.5% of all accesses to emergency room (ER) in the adult population . ConsideThe aim of the present observational study was to estimate the prevalence of primary and secondary headache in the population afferent to the four Advanced Medical Presidiums (AMPs), during the post-seismic emergency period. The secondary aim was to evaluate the frequency of use, types of pain killers and the short-term efficacy of the pharmacological treatment of the neurological pain.WHITE = No emergencyGREEN = Secondary emergencyYELLOW = Primary emergencyRED = Extreme emergencyBLACK = Death.The present observational study was carried out in four AMPs that were present in tent camps included in seven Mixed Operating Centers (MOC) operating in the area of L’Aquila during a 5-week period after the earthquake . AMP is a light pneumatic-tent structure, provided by the Department of Civil Defense, where a voluntary staff of doctors (2–3 MD/day) and nurses (2–3 Nurses/day) operates. The staff was on duty shifts of 8–12 h and provided healthcare assistance to the population. For triage, conventional emergency codes were employed:2) have been registered. State of consciousness by Glasgow Coma Scale (GCS) and pain intensity during cephalalgic crisis  by the verbal numerical rating scale (NRS) have been assessed. Neurological examination has been performed at baseline. Associated clinical conditions and previous and/or current therapy have been registered, including allergies, tobacco addiction, alcoholism and drug addiction. Finally, diagnosis of primary or secondary headache was made on the basis of a simple questionnaire  after drug administration for a short-term follow-up. The AMP centers were located in Bazzano, Tempera-S.Biagio, Onna and Paganica. Anesthetists in a common registry have collected data. All patients, including civilians, Civil Defense volunteers, Security force, soldiers and firemen afferent for the first time to the health structures have been considered for the study. Data are presented as mean and standard deviation, frequencies and prevalences in percentage. Statistical analysis used repeated-measures for NRS score analysis of variance (RM-ANOVA) and Bonferroni t test  as least significant difference test. P value of <0.05 was considered statistically significant.Demographic parameters, including name, surname, gender, age, physical conditions  have been registered for each patient. Also cardio-respiratory parameters, including blood pressure (BP), heart rate (HR), body temperature [BT (in °C)] and oxygen saturation (SpOn = 14), while the first episode was present in 74% of patients (n = 39). A quantitative estimate of pain intensity by the NRS scale at T0 showed an average intensity of 7 ± 1.1 (range 4–10). Antinflammatory drugs have been administered in 46% of cases, paracetamol in 36%, the association of weak opioids plus paracetamol in 11%, weak opioids in 7% , this means a 5-point difference in the NRS scale  and a 75% decrease compared to T0. Pain was controlled by pharmacological treatment in the following 2 days of observation. The percentage of patients on symptomatic treatment was 89% at T24h with a NRS score of 1.95 ± 0.75 and 77% at T48h. The average NRS score at T48h was 1.8 ± 0.68 , among the 958 first accesses to AMP, whereas secondary headache was 2.82% (95% CI 1.9–4.9)  as in the following 24–48 h (T24h and T48h). It is known that about two-third of patients complain new episodes of pain within 24 h after discharge from ER; in half of them, the intensity of pain is mild-severe [T48h = 1.8 ± 0.68). Figures The high frequency of first episodes of primary headache is another distinctive element that underlines the importance of chronicizing stress in the pathogenesis of this condition. The “central” mechanisms of the disease may have been triggered off, in particular, by peripheral mechanisms such as contraction, hypersensitivity, pain of pericranial and cervical muscles, secondary to the above-mentioned hard life context. Overall, these elements may be responsible for increase of chronic forms after the catastrophic event . Severald-severe . Up to 5d-severe . In the The present observational study has been markedly influenced by the adverse clinical setting in which it has been carried out and by the multifactorial pathogenesis of headache. The most important aspect of the study is that the observation of patients was protracted for 48 h, in a clinical condition characterized by shortage of sophisticated diagnostic instruments. The first steps for identifying primary headache in patients afferent to AMPs included an accurate medical history, a short questionnaire (no approved questionnaires for headache in ERs are available) and physical examination. Valuable information has been derived from vital parameters, such as body temperature, arterial blood pressure, cardiac frequency and NRS score. Further important diagnostic elements have been derived from physical examination, including palpation of the aching head and neck areas, and complete neurological examination. These simple elements allowed us to formulate a correct diagnosis and organize a therapeutic intervention for the following 48 h; this approach obtained a substantial control of pain in all primary forms. Specific potent drugs, including triptans and narcotic analgesics, were unavailable in our setting; this reveals a poor sanitary education and care in the treatment of headache and, more generally, of pain syndromes in emergency situations. This last consideration is of major concern due to the relevant prevalence of headache in natural disaster setting, the prognostic severity of secondary forms and the high risk of chronic headache.


Back pain is one of the major sources of disability in the US, but existing studies often have a restricted focus, leaving many patients unstudied.. The SPICER project is designed to assess the effect of integrative medical care in a mixed integrative/conventional clinic, using only existing electronic medical records, without any patient exclusions. This report will present information on which patient characteristics are good candidates to be used for adjustment or matching to reduce treatment selection bias.All diagnoses, visits, services, procedures, claims, and medications were extracted on 8,000 back pain patients from 2002 to 2009. Integrative medicine services were acupuncture, bodywork (including massage), and chiropractic. Event-stream data methods were used to construct analysis datasets containing potential matching factors: gender, age, year of first visit, comorbidities, combinations of 7 categories of back pain at first diagnosis, and use of integrative medicine prior to diagnosis of back pain.The volume of results is considerable, because no patients were excluded for having a complex medical record. In general, selection of integrative medicine for back pain was positively related to being female, being older, having used it before back pain diagnosis , strongly related to the complexity of the initial back pain diagnosis, and tending to decrease over calendar time.Identification of clinical variables that contribute to the propensity to use integrative medicine is vitally important for non-intervention research from medical records. All techniques for reducing treatment selection bias depend on them. The results reported here show that there is an adequate battery of matching factors that are in concert strongly related to choice of therapy.


Our aim was to estimate the prevalence of distal chronic pain with neuropathic characteristics in patients with type 1 and type 2 diabetes mellitus and its impact on quality of life, mood, anxiety, sleep and healthcare utilization.In total, 885 patients were screened and 766 diabetic patients  were enrolled consecutively over a three-month period in this observational study by 85 diabetes specialists working in a hospital department or in private practice. All the patients completed a series of questionnaires for the detection of chronic pain (i.e. daily pain for more than three months) in the lower limbs and assessment of health-related quality of life , sleep disturbances , depression and anxiety . Patients with chronic pain were also assessed with the 7-item DN4-interview questionnaire, the monofilament test and the Michigan Neuropathy Screening Instrument (MNSI).The overall prevalence of chronic pain with neuropathic characteristics was 20.3% [95% CI 17.4–23.1]. The MNSI examination score suggested that pain was related to polyneuropathy, in 80.1% of these patients . Patients with chronic pain had a poorer quality of life and more sleep disturbances, anxiety and depression than patients without pain and the presence of neuropathic characteristics was predictive of such impairments. Only 38.6% of the patients had received appropriate treatment for neuropathic pain.Chronic pain with neuropathic characteristics concerns one in five diabetic patients, has a significant impact on quality of life and is not adequately managed. The close correlation between the DN4 questionnaire and MNSI results suggests that screening tools for neuropathic pain could be used in daily practice for the identification of painful diabetic polyneuropathy. Sensory distal polyneuropathy is a common complication of diabetes, affecting about 50% of the patients. It may have severe complications, including foot ulcers, amputation and chronic pain Pain associated with diabetic polyneuropathy is, by definition The primary objective of this observational study was to estimate the prevalence of distal (lower limbs) chronic pain with neuropathic characteristics  Ile de France 1, and all patients provided written informed consent before enrollment. Patients were enrolled consecutively over a three-month period (up to 10 patients per center) by diabetes specialists working in a hospital department or in private practice. The inclusion criteria were: patient with type 1 or type 2 diabetes mellitus, over the age of 18 years, with a good understanding of French and with a HbAData were collected through standardized questionnaires. The investigators recorded patients’ demographics, diabetes characteristics, complications, treatments and cardiovascular risk factors. The patients were then asked to report any pain they were suffering in their feet and/or legs and its duration. If the patients reported chronic pain in the lower limbs, defined as daily pain for at least three months, the investigator recorded the treatments for pain received by the patient and administered the DN4 questionnaire, the monofilament test and the MNSI (Michigan Neuropathy Screening Instrument) (see below), before finally noting the cause of pain, according to their own clinical judgment.All the patients (with and without pain) were asked to complete a series of questionnaires to assess health-related quality of life, sleep disturbances and anxiety and depression (see below). The patients with chronic pain, were asked to rate the mean intensity of pain over the previous week on a numerical rating scale , to specify its location, its duration and who they had consulted for this pain.The DN4-interview questionnaire was used to identify neuropathic characteristics of pain. This questionnaire has two questions, comprising seven items: three items relating to pain quality and four items relating to associated paresthesia/dysesthesia. Patients with a score ≥3 were considered to have pain with neuropathic characteristics The 10-g Semmes-Weinstein monofilament test was performed, as described by Perkins et al. The MNSI The assessment of quality of life in patients with and without pain was based on the Medical Outcomes Short Form 12 scale (MOS SF-12) Continuous variables, which had all a normal distribution, are described as means ± SD; categorical variables are expressed as frequency distributions and percentages for the relevant subject groups, with 95% confidence intervals. Missing data were not considered in the expression of the results.Pain intensity scores of 1 to 3 were considered to indicate mild pain, scores of 4 to 6 were considered to indicate moderate pain, and scores of 7 to 10 corresponded to severe pain.1C level, diabetes complications, risk factors) potentially predictive of chronic pain with neuropathic characteristics. The variables significant in the univariate analysis, at a threshold of at least 20%, were entered into a septwise multivariate logistic regression model and the odds ratio for significant factors was calculated with a 95% confidence interval (CI). One-way analyses of variance (ANOVA) were used to compare the scores for quality of life (SF-12), sleep disorders (MOS-Sleep) and mood disorders (HADS) between the various groups of patients. A logistic regression analysis was used to identify the factors  predictive of an altered SF-12, HADS or MOS-Sleep scores. Stepwise logistic regression models were used, as described above, to identify factors independently predictive of alterations of these scores. Data were analyzed with SAS version 9.1 software .A logistic regression model was used to identify the factors  or type 2 (61.2%) diabetes included in the study are summarized in In total, 249 patients reported chronic daily pain for more than three months in the distal lower limbs, giving a prevalence of 32.5% [95% CI 29.2–35.8]. The prevalence of chronic pain was significantly (p<0.01) higher in patients with type 2 diabetes (40.0% [95% CI 35.6–44.4]), than in patients with type 1 diabetes (21.5% [95% CI 16.8–26.2]).The DN4-interview results see  showed tMean pain intensity over the last week was 5.3±2.3 and 76.2% of the patients reported pain of moderate to severe intensity (i.e. NRS score ≥4) . ChronicThe MNSI-examination score obtained suggested the presence of polyneuropathy in 80.1% of the patients with neuropathic characteristics (83.7% of those with type 1 diabetes and 78.8% of those with type 2 diabetes). The proportion of patients with a MNSI-examination score >2 was of 89.5% for patients with bilateral chronic pain. These results, suggesting that distal pain with neuropathic characteristics, particularly when bilateral, is related to polyneuropathy in most patients, were consistent with the investigators’ clinical judgment, with investigators reporting that pain was related to a diabetic polyneuropathy in 91.8% of these patients.By contrast, only 43.2% of the patients with chronic pain with neuropathic characteristics had an MNSI-questionnaire score suggestive of polyneuropathy (i.e. score ≥7/13), and a similar proportion (48.7%) had an abnormal result for the 10-g monofilament test.Nearly 20% of the patients with chronic pain with neuropathic characteristics (n = 31), that is 12.4% of the patients with chronic pain, had no neurological signs according to the results of the MNSI-examination and monofilament test.Univariate analyses showed that several factors, including older age, type 2 diabetes, the presence of other diabetic complications, a history of foot ulceration, higher total and HDL cholesterol levels, higher triglyceride concentration, a history of alcoholism and a higher BMI, were associated with a higher risk of chronic neuropathic pain in the lower limbs see . MultivaPatients with chronic pain had significantly lower physical and mental health subscores for the SF-12, greater impairment of sleep quality and higher anxiety and depression scores see . PatientThe multivariate analyses showed that:1c level ≥7% (OR = 2.01 [95% CI: 1.01–4.02]) and a BMI ≥30 kg/m2 (OR = 2.53 [95% CI: 1.38–5.62]).The independent factors predictive of a lower physical component of quality of life (SF-12 questionnaire) were: being female (OR = 2.33 [95% CI: 1.18–4.56]), a pain intensity>4 (OR = 5.94 [95% CI: 2.43–14.48]), the presence of foot wound/ulceration (OR = 6.76 [95% CI: 2.33–20.48]), a HbAThe independent factors predictive of a lower mental component of quality of life (SF-12 questionnaire) were: being female gender (OR = 2.62 [95% CI: 1.46–4.67]), a DN4 score ≥3 (OR = 3.81 [95% CI: 2.17–6.68]) and a triglyceride concentration >1.6 mmol/l (OR = 2.02 [95% CI: 0.94–4.29]).The independent factors predictive of a lower quality of sleep were: a DN4 score ≥3 (OR = 3.22 [95% CI: 1.71–6.06]), a pain intensity >4 (OR = 4.47 [95% CI: 1.98–10.12]) and an age <49 years (OR = 5.30 [95% CI: 1.90–13.70]).The independent factors predictive of a higher score for anxiety (HADS-A) were: a DN4 score ≥3 (OR = 3.2 [95% CI: 1.72–5.96]), a pain intensity >4 (OR = 2.3 [95% CI: 1.06–4.89]) and a triglyceride concentration >1.6 mmol/L (OR = 3.87 [95% CI: 1.82–8.20]).2 (OR = 1.94 [95% CI: 0.98–3.82]) and a MNSI-questionnaire score ≥7 (OR = 2.20 [95% CI: 1.15–4.13]).The independent factors predictive of a higher score for depression (HADS-D) were: a DN4 score ≥3 (OR = 4.38 [95% CI: 2.27–8.47]), a BMI ≥30 kg/mAbout three quarters (72.7%) of the patients with chronic pain with neuropathic characteristics had previously consulted for their pain. Most had consulted a general practitioner (69.9%) or a diabetologist (65.6%), with smaller proportions consulting a neurologist (26.6%), a rheumatologist (16.8%) or a pain specialist (4.6%).More than two thirds (68.9%) of the patients with neuropathic pain received treatment for their pain. However, only 38.6% of these patients were treated with at least one of the recommended first-line treatment: antiepileptic drugs (24.5%) and/or antidepressants (16.9%).This cross-sectional observational study, the largest to date on this topic to be carried out in France, indicate that one in five diabetic patients suffers daily pain with neuropathic characteristics, in the legs and/or feet, over periods of at least three months. Our data also show that chronic pain with neuropathic characteristics has a major impact on quality of life, mood, anxiety and sleep and that only a minority of patients receive one of the recommended first-line treatments for neuropathic pain. Finally, our finding suggest that screening tools for neuropathic pain such as the DN4 questionnaire, may be of value for the systematic screening of diabetic patients for polyneuropathy.Our overall estimate of the prevalence of distal neuropathic pain in diabetic patients is consistent with previously reported values of the prevalence of painful diabetic polyneuropathy (PDPN), despite the use of different diagnostic criteria in different studies. Three studies carried out in community-based samples in the UK provided estimates of 16.2% In general, our approach, based on validated questionnaires and standardized neurological examination (i.e. MNSI and the monofilament test), was similar to that used in these studies. However, we gave priority to the patients’ symptoms  in our case definition. Neuropathic pain has been shown to have particular clinical characteristics that can be identified with simple, easy-to-use clinical tools based on the analysis of the terms used by the patients to describe their pain (i.e. pain descriptors) A few other epidemiological surveys in diabetic patients have used screening tools for neuropathic pain. Two studies carried out in the Middle East Area and based on the DN4 questionnaire reported higher prevalence rates than in our study. In one study carried out Saudi Arabia The main risk factors for chronic neuropathic pain identified here are similar to those previously reported for painful diabetic neuropathy Relatively few studies have specifically assessed the impact of neuropathic pain on the health-related quality of life (QoL) and psychological comorbid conditions of diabetic patients The unmet needs regarding the management of neuropathic pain, which are not specific to diabetic patients


Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST).This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups.64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation.Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain.NCT00755573ClinicalTrials.gov  The treatment of chronic pancreatitis patients can be a major clinical challenge. One of the main factors contributing to this problem is the lack of evidence regarding the origin of chronic pancreatitis pain. Medication targeting altered central pain processing, e.g. gabapentinoids such as pregabalin, has been used successfully to treat other chronic pain disorders such as post-herpetic neuralgia and neuropathic pain of central origin.The aim of the present study is to evaluate the effect of pregabalin as adjuvant pain treatment on pain processing, measured by somatic QST, in patients with chronic pancreatitis. We hypothesized that the hyperalgesia in chronic pancreatitis patients with pain will undergo reduction under pregabalin treatment, but not under placebo treatment.The protocol for this trial and supporting CONSORT checklist are available as supporting information; see This study was part of an investigator initiated double blind, placebo-controlled, parallel-group study of increasing doses of pregabalin conducted in the Netherlands  and Denmark . For trial inclusion, patients needed to have chronic abdominal pain typical for pancreatitis (i.e. dull epigastric pain more than 3 days per week for at least 3 months) and a diagnosis of chronic pancreatitis based on the Mayo Clinic diagnostic criteria. Clinical endpoints i.e. pain scores and side-effects of the main study are presented in more detail in the original manuscript. A control group was recruited in Denmark for comparison with our chronic pancreatitis group to confirm the presence of spreading hyperalgesia at the baseline pre-medication measurement in the pancreatitis group. The controls were completely healthy and had no history of a medical condition that could interfere with our pain measurements.Eligible patients at our outpatient departments were randomly assigned in a one to one ratio to receive either pregabalin or placebo. A pseudo-random code was computer generated for the randomization blocks that had a size of six. Stratification of trial participants was based on the absence or presence of diabetes mellitus to minimize unbalance in distribution of undiagnosed diabetic polyneuropathy. Patients received increasing doses of either pregabalin or matching placebo for the study period of 3 weeks. Initial dose was 75 mg pregabalin twice a day (BID). After three days this was increased to 150 mg pregabalin BID, with a further increase to 300 mg BID after one week and for the rest of the study period. An equivalent regime was followed in the placebo arm. The same oral dosing schedule was prescribed to all patients. Daily dosages were split into two equivalent doses, one administered in the morning between 7 a.m. and 10 a.m. and one in the evening between 7 p.m. and 10 p.m. In the case of unacceptable side effects experienced by patients, a single downward dose titration was allowed. Patients had to stay on that final dosage for the remaining study period. Patients were instructed to taper their study medication after three weeks of treatment, by halving their dose for seven days, and then to stop medication. Patients and those administrating study medication, assessing outcomes, and analyzing data were blinded to group assignment.Patients considered for participation in this trial were screened for eligibility and physical fitness. A systematic physical examination including a neurological examination was performed to assess for any relevant conditions and neurological disorders. If eligible, they were randomized by their treating physician for placebo or pregabalin on their second visit, one week after their screening visit. During their second visit all patients had a baseline QST measurement, followed by another QST measurement at the end of the study period of three weeks, i.e. before they were instructed to taper their medication. During the whole study period patients were instructed not to change their daily pain medication. They were only allowed to take extra pain medication in the case of a painful exacerbation of their chronic pancreatitis.QST took place using a standard temporal test sequence. 2 probe , at each of the following sites on the dominant body side: clavicle (C5 dermatome), sternum (T4 dermatome), pancreatic site , hip region (L1 dermatome) and knee (L4 dermatome)  . The panThresholds to electric constant current skin stimulation  were measured on the dominant side of the body at the same sites as for pressure pain thresholds. Two thresholds were measured: electric pain detection threshold (ePDT) and electric pain tolerance threshold (ePTT). As the primary endpoint, the sum of all the thresholds was again calculated. The conditioned pain modulation ) paradigm was performed to test the ability of the patient to generate descending inhibitory modulation. The primary effect parameter for the study was the between group difference (change) in sum of electric or pressure pain thresholds after three weeks of study medication vs. baseline values. pre hoc power calculation based on QST as an endpoint was not performed because the study was a part of a randomized clinical trial that investigated pregabalin, powered for a clinical primary endpoint; i.e. change in clinical pain score.A For this mechanistic study we performed an intention to treat analysis. We performed statistical analysis using the Statistica for Windows Software Package . All baseline characteristics and measurements are given as medians with interquartile ranges. In view of the non-Gaussian data distribution purely non-parametric analysis was performed. Statistical significance was set at P≤0.05.The sum of all dermatomes for electric and pressure pain detection and tolerance thresholds and the conditioned pain modulation results were compared between the control and the study group using Mann Whitney U testing to confirm spreading hyperalgesia and pro-nociceptive pain modulation shift in the pancreatitis patients. We calculated differences (change) in sum of thresholds or individual thresholds between values at pre-medication baseline and after three weeks’ medication. We then compared these differences between the groups using Mann Whitney U testing. Further analysis consisted of comparison of placebo vs. pregabalin groups at pre-medication baseline and after three weeks’ treatment for the sum of thresholds, for individual thresholds, or for conditioned pain modulation values using Mann Whitney U testing.From October 2008 to May 2010 a total of 236 patients diagnosed with chronic pancreatitis in the last five years in one of both hospitals were screened and 64 patients were randomized; the study was completed without any incident. The majority of patients not meeting inclusion criteria were free of pain, had passed away or were no longer being treated in either of the hospitals. 64 patients completed the study and were finally analyzed in the intention to treat analysis . The numThe sum for pressure and electric pain detection and tolerance thresholds of all dermatomes was significantly lower for the pancreatitis group at baseline vs. healthy controls . At baseThe sum of all dermatomes for pressure and electric pain detection and tolerance thresholds at baseline was similar for the pregabalin vs. placebo groups . The samAt baseline, patients in the placebo group tolerated the cold pressor task for 32 seconds (IQR 23–98) and in the pregabalin group for 40 seconds (IQR 23–60), this was not statistically different between groups. Also no significant difference was found in baseline CPM response between the placebo and pregabalin group .sums of electric pain detection and tolerance thresholds between the groups (There was no significant difference in differences (change) in e groups .individual electric pain detection thresholds, difference (change) in dermatome C5 was significantly higher in the pregabalin group , with a trend for T10 (P = 0.055) (For = 0.055) .individual electric pain tolerance thresholds, threshold differences (change) for dermatome C5  and L1  were significantly higher in the pregabalin group (For in group .sums of pressure pain detection and tolerance thresholds between the groups (There was no significant difference in differences (change) in e groups .individual dermatomal pressure pain detection thresholds between the groups (There was no significant difference in differences (change) in e groups .individual pressure pain tolerance thresholds, threshold differences (change) for dermatome T4  were significantly higher in the pregabalin group (For in group .The difference (change) in cold pressor task latency and CPM response was not significantly different between the study groups .sum of all dermatomes for electric pain detection thresholds was significantly higher in the pregabalin vs. placebo group (P = 0.01), but not for electric pain tolerance thresholds   and L1 (P = 0.03) were significantly higher in the pregabalin group.For  = 0.05) . For indSums of – or individual dermatome – pressure pain detection and tolerance thresholds were similar between groups (n groups  and 4 afAfter three weeks of study medication patients in the placebo group tolerated the cold pressor task for 42 seconds (IQR 21–116) and in the pregabalin group for 46 seconds (IQR 27–77); this was not statistically significant. Also no significant difference could be found between groups for CPM response after study medication .Our study is the first to demonstrate that a three-week treatment with pregabalin in chronic pancreatitis patients results in a moderate antihyperalgesic effect compatible with a reduction of central sensitization. A shift toward more anti-nociceptive pain modulation appears less likely as mechanism due to the unaltered conditioned pain modulation (CPM) response. Interestingly, this early treatment effect is 1) visible only in dermatomes distant from the referred pancreatic area, and 2) more pronounced for electric skin thresholds than for pressure muscle thresholds. This implies 1) better effects on distant as compared to segmental central sensitization and 2) more effective hyperalgesia reduction in skin compared to deeper tissues. These results suggest that measuring pain sensitivity using quantitative sensory testing (QST) may prove useful in monitoring the effects of pain treatment in chronic pancreatitis and help us to diagnose and manage altered pain processing in chronic pain disorders.Nociceptive input from the pancreas spreads via ascending pathways to spinal and supraspinal central nervous system structures in chronic pancreatitis. The treatment of pain in chronic pancreatitis patients is usually based on the WHO pain treatment ladder, which ends with opioid treatment. Opioids can provide effective analgesia in some pancreatitis patients, but may have considerable side effects or even induce hyperalgesia. In this study we failed to show a significant difference between groups regarding our primary outcome measure (change in sum of thresholds). The significant result regarding secondary outcome measure  suggests a moderate effect on spreading hyperalgesia. Interestingly, antihyperalgesic treatment with pregabalin resulted in a greater increase of electric pain thresholds than of pressure pain thresholds after three weeks treatment. A possible explanation is that pregabalin is initially more effective in reducing skin sensitization, as reflected by electric thresholds, as compared to deep tissue sensitization, as reflected by pressure thresholds. In this study no significant improvement in conditioned pain modulation (CPM) could be found, suggesting that the main effect of pregabalin is to directly target central sensitization reflected by hyperalgesia, rather than the pro/anti-nociceptive balance of endogenous modulation. We did, however, demonstrate that before treatment, pancreatitis patients showed less inhibitory pain modulation than healthy controls in accordance with other studies. A limitation of this study is the relatively small size of the chronic pancreatitis group. A larger sample of chronic pancreatitis patients would appear necessary to provide more detailed and significant evidence of the relation between pregabalin treatment, changes in pain scores and changes in hyperalgesia. While we did find parallel, separate reductions in pain scores and pain sensitivity in our patient collective, the study was not adequately powered to formally study – or prove – correlations between clinical pain reduction and reduction in hyperalgesia. Definitive proof of such a relationship awaits future larger and longer-lasting trials. It should be noted that most chronic pancreatitis studies are small due to the difficulties in recruiting large groups of uniform chronic pancreatitis patients. Better and larger national and international collaborations are necessary to permit larger and longer population based trials in chronic pancreatitis.In this study an intention to treat analysis was performed conform the international standard for randomized clinical trials. It can be argued that for the mechanistic endpoints an analysis including only patients fully compliant with the study protocol should be performed . We therefore also performed a per protocol analysis, but we did not present these data in this manuscript, because there were no major differences compared to the intention to treat analysis. Another limitation of the study is the absence of a long-term follow-up. We only measured effects after a relatively short treatment period of three weeks. At this time, modest reductions in distant skin hyperalgesia were already noticeable and significant, albeit without return to normal values . This reduction in hyperalgesia occurred in a patient population with a long history of chronic pancreatitis, generally regarded as being particularly difficult to manage.In conclusion our study provides first evidence that pregabalin modestly reduces the spreading hyperalgesia as manifestation of central sensitization associated with chronic pancreatitis pain. This effect was evident after three weeks of pregabalin treatment and was most evident for electric skin pain thresholds. However more research is needed to predict the long-term effects and define effective dosage schemes for pregabalin use in different stages of chronic pancreatitis.Checklist S1CONSORT checklist.(DOC)Click here for additional data file.Protocol S1Trial protocol.(DOC)Click here for additional data file.


Migraine is the most frequent primary headache, one of the main complaint of our neurological out-patients department, but it has not been studied enough in our structure.We aimed to assess clinical features of migraine in a sub-saharian teaching hospital.We carried out a prospective study in the out-patient department of the neurological service of Fann teaching hospital, in Dakar.One hundred patients were collected, aged from 9 to 64 years with sex-ratio 5.25. It was migraine without aura in 83% of patients and with aura in 17%. Triggering factors were mainly psychical, climatic, hormonal, food, fatigue, physical effort, sensorial. The pain was hemicranial in 73%, throbbing in 82%, tightening or itching in 18%. Headache duration varied from 4 to 72 hours in 75%, less than 4 hours in 10%, more than 72 hours in 15%. Pain intensity was mild for 2%, moderate for 49% and severe for 49%. It occured once a day to less than once a month. Photophobia was found in 78%, nausea in 48%, vomiting in 33%. Aura was visual, psychical or sensorial. All patients benefited from treatment of acute pain, while 83% underwent permanent treatment in addition. Fifty eight per cent of women who had already been pregnant reported improvment during pregnancy.Of yhe whole sample, 59% had never seen a doctor for their migraine, using self-treatment or not pain-killer at all. Fifty three per cent of patients experienced a good outcome, while it was sationary for 31%, 17% being lost sight.Even if it is less studied in Africa, and is supposed to be less frequent in black people , migrain


Abdominal migraine (AM) is an idiopathic recurrent disorder occurring primarily in children. Because their abdominal pain may be so intensive to interfere with their normal activity and AM is recognized as migraine prodrome, it is important to make the exact diagnosis, appropriate managements and close follow-up the symptoms. We therefore analyzed the clinical characteristics of AM and risk factors for developing migraine later.The 923 children with recurrent abdominal pain (RAP) visited our hospital from Jan 2006 to Dec 2010. Among them we retrospectively studied 84 children fulfilled ICHD-II criteria for AM. Through chart review and telephone interview, we evaluated the clinical characteristics of AM and divided them into two groups by developing for migraine (group A) or not (group B). By comparing the groups, we tried to find the risk factors for developing migraine later.About 8.9% of patients with RAP were diagnosed as AM. Their mean age was 7.1± 3.0 years . The frequency of abdominal pain was 4.3± 2.4/week and the duration of abdominal pain was about one hour (0.5~2.0). The symptoms associated with abdominal pain were anorexia , nausea , vomiting , pallor  and headache . 27 (32.1%) patients with AM were suffer from migraine 1.7±0.8 years later from onset of AM, and their mean age was 8.3± 3.2 years . When the clinical characteristics were compared to each other between group A (n=27) and group B (n= 57), there were no differences in age, gender, frequency, duration etc. But AM patients with headache significantly developed migraine later (P = 0.003). AM patients who needed drug therapy significantly developed migraine later (P=0.034).32.1% of AM patients developed migraine. And the risk factors for developing migraine were headache associated with AM and general impression by physician that need pharmacologic therapy.


Background. New studies in the management of knee osteoarthritis have focused on modern therapeutic methods stimulating cartilage healing process. In the present study, we evaluated the effects of 2 courses of leucocyte-rich PRP (LR-PRP) injections on patients' QOL and functions and also the relationship between the PRP concentration and mentioned variables. Material and Methods. Sixty-five patients were evaluated. For each participant, WOMAC and the native (Farsi) edition of the SF-36 questionnaire were filled. Two courses of LR-PRP injections with 4-week interval were used. After 6 months, SF-36 and WOMAC questionnaires were filled again for each patient. Results. 60 patients were included in the final analysis. The mean platelet concentrations and white blood cell in PRP was 5-fold increase and 220 per microliter, respectively. The mean total WOMAC revealed significant change (P = 0.001). In SF-36, the mean changes of 2 major physical and mental domains were meaningful (P = 0.001). Discussion. In our study, 2 injections of PRP, with 4-week interval, improved the pain, stiffness, and functional capacity. Improvements in QOL (both PCS and MCS) were meaningful after injections. These changes were more significant in physical domains. PRP injection may be an alternative therapy in selective patients resistant to current nonsurgical treatments of knee osteoarthritis. Osteoarthritis, the most common articular disease in humankind, results from defects in articular cartilage and has significant effects on the quality of life (QOL) of patients, especially the elderly. For this reason, the effects of osteoarthritis and related therapeutical interventions on the QOL and patients' functions have been assessed in different studies .There are different methods used for alleviating the symptoms of patients with knee osteoarthritis (OA), including various medications and supplements , intra-articular injections , physical agents , and surgical interventions –4. AlthoConsidering the aforementioned issues, new studies have focused on modern therapeutical methods stimulating cartilage healing process and improving its damage, including application of matrix metalloproteinase inhibitors, gene therapy, cytokinase inhibitors, stem cells, and growth factors . Growth There are extensive ongoing studies about the effects of PRP on knee OA, some of which were pilot studies , 22. In In this clinical trial, patients with knee OA referring to the Physical Medicine and Rehabilitation Clinic in Shahid Modarres Academic Hospital in 2011 were evaluated. Inclusion criteria were arthralgia since the past 3 months with radiologic evidence of articular damage   based onAfter selecting patients, targets, and method of conduction and presenting scientific evidences, benefits and possible complications of participating in the study were described by a physiatrist verbally and written information about mentioned issues was also presented. After signing the consent form , they were included in the study. Patients' personal information such as age, gender, height, weight, BMI (body mass index), educational level, physical activity, symptom duration, and the grade of OA  were registered. Then, for each participant the native (Farsi) editions of the SF-36 (Short Form-36) questionnaire for assessment of QOL and WOMAC (Western Ontario and McMaster Universities Arthritis Index) questionnaire for evaluation of patients' functions were filled by a physical medicine and rehabilitation resident. The SF-36 questionnaire is one of the most common and comprehensive questionnaires used as a standard health outcome measurement tool on international level. It contains two major domains: physical health and mental health. Each domain has 4 subcategories consisting of physical functioning, physical role, bodily pain, and general health for the physical component summary or physical health category; social functioning, emotional role, mental health, and vitality in the mental component summary or mental health aspect. Higher scores in this questionnaire imply better patient status .The WOMAC questionnaire is among the tools used for evaluation of patients' functions in rheumatic diseases especially knee OA. Three domains of stiffness, pain, and functional limitation are measured in this questionnaire. Higher scores in this regard imply worse patient status .For the process of PRP preparation and injection, participants were referred to Shahid Modarres Hospital Laboratory. The PRP processing was done using the Rooyagen kit . For preparing 4–6 mL of PRP with concentration of 4–6 times the average normal values, 35–40 mL of blood was first collected from the patient's upper limb cubital vein using an 18 G needle. Then, 5 mL of ACD-A was added to the sample as an anticoagulant. One mL of the blood sample was sent for complete blood count. The rest of the sample passed two stages of centrifuge (first with 1600 rpm for 15 minutes for separation of erythrocytes and next with 2800 rpm for 7 minutes in order to concentrate platelets). The final product was 4–6 mL of PRP containing leukocytes. The PRP quantification and qualification procedure was performed using laboratory analyzer Sysmex KX 21 and swirling and if approved, the injection was proceeded. As it was stated in some resources that anesthetic agents not only could have toxic effects on chondrocytes but also by changing the pH of the environment could influence the activation of platelet, no local anesthetic agent was injected [Then, participants were sent home with a written order concerning the following issues. They were recommended to have relative rest 24 to 48 hours after injection and limit weight bearing on the injected joint. Meanwhile for reducing pain and inflammation, they were instructed to use cold therapy three times a day each time for 10 minutes. In the case of pain onset, they had permission to use 500 mg of acetaminophen and if persistent, acetaminophen-codeine could be used PRN. However, they were strictly prohibited to take NSAIDs, aspirin, or any steroids. Generally, participants were recommended to have mild-to-moderate levels of activity and increase it as tolerated. They could resume their usual activities of daily living (ADL) one week after injection. Meantime they were instructed with exercise therapy and ADL modifications.There is no consensus about standard regimen of PRP treatment in musculoskeletal disorders. In different study protocols, average series of injection is two to three at two- to six-week intervals , 23. Bect-test, independent t-test, and ANOVAs test were used. To evaluate nonnormal variables, nonparametric tests of Wilcoxon signed rank, Mann-Whitney, and Kruskal Wallis were applied. Qualitative variables were expressed with frequency and percent. For evaluating the relationship between quantitative variables, correlation coefficients of Pearson and Spearman were used.Final data before and after the treatment were imported and analyzed by SPSS v. 16. Normality of the data described by mean and variance was evaluated using Shapiro-Wilk's test. For comparing variables with normal distribution, paired 2. Demographic data of the patients are demonstrated in Sixty-five patients were evaluated in this study. Five patients were excluded from the study, 3 due to concomitant use of NSAIDs, 1 due to failure to participate in follow-up program, and 1 due to lack of interest to continue with treatment. Finally, 60 patients were included in the final analysis including 52 women (93.3%) and 4 men (6.7%). The mean age of participants was 56.90 ± 8.8 years. The mean BMI was 28.46 ± 4.59 kg/mPRP preparations in this study contained leukocytes (LR-PRP). The most important patients' complaint was injection site pain. In some cases, pain lasted up to 10 minutes after injection, decreased gradually, and continued as a dull pain at the injection site. Some patients complained of transient knee stiffness and even local pelvic pain and feeling of swelling. Pain in most of them was improved by following the instructions and acetaminophen consumption. No significant complication was observed except for transient increase in local pain and swelling.P = 0.001). The changes in all WOMAC subcategories were meaningful as demonstrated in P = 0.001).The mean total WOMAC before treatment was 39.12 ± 16.25 and 21.05 ± 14.73 after treatment which experienced meaningful change (P = 0.001). The mean change for mental component summary (MCS) before and after treatment was 51.11 ± 19.81 and 62.09 ± 22.09, respectively. The mean change for physical component summary (PCS) before and after treatment was 43.22 ± 16.36 and 62.02 ± 18.76, respectively.In SF-36, the mean changes of 2 major physical and mental domains were meaningful .The amount of improvement in pain, stiffness, and functional capacity  had no meaningful relationship with any of the primary parameters   while others lacked this relationship (P > 0.05).The relationship between improved QOL  and primary parameters  was evaluated and only the mean change of pain had relationship with age (P > 0.05). There was also no meaningful relationship between the mean concentration of platelets in PRP in first and second injections and mean improvement values of total WOMAC and SF-36 domains (P > 0.05).The amount of improvement in joint pain, stiffness, and function and QOL had no relationship with patient's primary weight  were meaningful after injections. These changes were more significant in physical domains (PCS) including role limitation due to physical health, pain, and physical functioning. Our results were similar to the study of Wang-Saegusa et al. . They evKon et al. evaluated the effects of PRP in short- (6 and 12 months) and long- 24 months) term in 2 separate studies. Similar results were obtained using IKDC questionnaire and VAS evaluation as assessment tools , 4. months tIn another study conducted by Kon et al., PRP, low- and high-molecular-weight hyaluronic acid were compared . PRP wasIn the study of Patel et al. comparing the effects of single and two injections of PRP with normal saline injection (as control) in knee OA, a single injection of PRP was shown to be as effective as two injections and both were more effective than normal saline injection .In our study, we analyzed the mentioned changes in WOMAC and SF-36 domains with demographic variables. None of them  has effect on the responses of the WOMAC and related parameters. A significant reverse relationship was found between patient's age and degree of pain reduction. Similarly, in the studies of Kon and Filardo, less reduction in IKDC scores was observed with advanced age. The observation of less responsiveness to PRP injection in advanced ages can be explained by the reduced number of available active and alive cells in order to react with growth factors. Furthermore, we evaluated the variable improvement results based on weight changes and found that there was no relationship between the amount of improvement in QOL, function, and weight changes. In contrast to our study, the amount of improvement was less with higher BMI . The difIn our study, although the clinical response rate was conversely related to severity of osteoarthritis, it was not statistically significant. This finding was not in agreement with other similar studies , 4. It mIn our study, the mean concentration of platelets in PRP was 3 to 7.8 times in the first injection and 2.4 to 8.6 times in the second injection. No relationship was found between the amount of improvement in pain, stiffness, functional capacity and QOL, and platelet concentration. Some studies mentioned that PRP could be effective in musculoskeletal diseases only in platelet concentrations of 4–6 times and concentrations of more than 8 times and less than 4 times had no such effect , 18, 24.Generally, our study like others proposed the effectiveness of PRP in short term , 34, 35.Among the limitations of our study were the lack of control group and the relatively small sample size. The best PRP concentration, long-term effects, the number of injections and the intervals between, and the cost effectiveness of PRP are issues that necessitate more studies in comparison to control group and other current treatments. In addition, performing objective studies such as MRI and pathologic assessments would be useful in evaluation of PRP effectiveness in patients with OA.Our study showed that intra-articular knee injection of PRP can decrease joint pain and stiffness and improve patients' QOL in short term. Therefore, PRP injection may be an alternative therapy in selective patients resistant to current nonsurgical treatments.


P = 0.000). Overall mobility improved in 18/18 (100%) patients. No complications were observed. During follow-up period , all patients underwent a mean of 1.3 sessions for facet joint and nerve root infiltrations. Percutaneous vertebroplasty in the inner arch seems to be an effective technique for supporting adult degenerative scoliotic spine.We evaluate the efficacy-safety of percutaneous vertebroplasty (PV) as primary treatment in adult degenerative scoliosis. During the last 4 years, PV was performed in 18 adult patients  with back pain due to degenerative scoliotic spine. Under anaesthesia and fluoroscopy, direct access to most deformed vertebral bodies was obtained by 13G needles, and PMMA for vertebroplasty was injected. Scoliosis' inner arch was supported. Clinical evaluation included immediate and delayed studies of patient's general condition and neurological status. An NVS scale helped assessing pain relief, life quality, and mobility improvement. Comparing patients' scores prior to , the morning after , at 12 , and 24 months after vertebroplasty  treatment, patients presented a mean decrease of 6.39 ± 1.6 NVS units on terms of life quality improvement and pain relief ( Adult scoliosis is a term referring to spinal deformity with a Cobb's angle on frontal plain equal or greater to 10° which appears on adult patients whose skeletal maturity is complete . Clinica Percutaneous vertebroplasty was introduced by Galibert and Deramond 1984), and the first report ever was published in 1987, concerning the treatment of a painful and aggressive vertebral body hemangioma in the cervical spine 84, and t–17. Based on percutaneous vertebroplasty's efficacy in pain reduction, application of this technique to the most deformed vertebral bodies was evaluated in a consecutive series of patients suffering from back pain due to adult degenerative scoliosis. All patients were informed about their inclusion in the study. Furthermore, they were informed upon the technique itself as well as possible benefits and complications, and they signed a written consent form to both the study and the procedure. The study received approval from the review board of our institution. During the last 4 years, percutaneous vertebroplasty (PV) was performed in 68 vertebral bodies of 18 adult patients (age range 44–92 years) with back pain due to degenerative scoliotic spine.  Inclusion criteria included adult patients capable of providing consent capable of complying with the study protocol, and suffering from back pain due to adult degenerative scoliosis. Pain was unresponsive or minimally responsive to conventional treatments for at least 3 months. Clinical and imaging examination defined proper patient selection. Percutaneous vertebroplasty was performed on sites where local percussion over the posterior elements of the involved vertebral body elicited pain, and this positive spinous process percussion was combined with imaging modalities verification (presence of bone oedema at the level of interest on STIR sequences of magnetic resonance scan) . Each patient underwent evaluation of all imaging studies, physical/clinical examination, and coagulation laboratory tests at least 24 hours prior to PV. Preoperational imaging included X-rays  and recent (up to 3 months old) multiplanar MRI . In selected cases where MRI was contraindicated  bone scintigraphy combined with Computed Tomography scan was performed. Exclusion criteria for the procedure included lack of positive percussion of spinous process combined with presence of bone oedema at the level of interest, uncontrolled bleeding disorders, any ongoing systemic or spinal infection, myelopathy, and/or neurological deficit. Significantly reduced vertebral body height (vertebra plana), destruction of the posterior vertebral wall, and retropulsed bone were not considered exclusion criteria as long as there were not any neurological symptoms.  Detailed description of the vertebroplasty technique  is beyon CT scan assessed implant's position after treatment. All patients underwent control CT during the first 24 hours after PMMA injection . Clinica Pain prior, the day after vertebroplasty, and during the 2-year follow-up period was recorded by means of NVS questionnaires. Numeric Visual Scale (NVS) is a 10 cm scale from 0 to 10 divided into ten equal parts (with a number corresponding to each part), upon which the patient subjectively assigns his/her pain on a score of minimum 0 (no pain) to maximum 10 (worst pain patient can imagine). In addition, the inventory contains questions concerning the pain itself and its influence upon patient's activity  and mobility impairment.  We considered as statistically significant improvement in numeric pain scores a decrease of at least 4 NVS units. Pain-free patients were considered the ones with NVS score of 0. All patients included in the study met the inclusion criteria.t-test. The threshold defining statistical significance was P < 0.05.Mean value, median value, and standard deviation of the self-reported pain scores prior, and after vertebroplasty were evaluated using related samples Wilcoxon signed-rank test and paired samples Statistical analysis was performed using SPSS for Windows (versions 17.0 and 21.0). IBM SPSS Sample Power 3 was used to calculate the statistical power of the study.  The mean volume of injected cement for all 68 treated vertebral bodies was 2.624 ± 0.9328 cc (range 1.0–6.0 cc). P = 0.000) , the morning after , at 12 , and 24 months after vertebroplasty  treatment, patients of our study presented a mean decrease of 6.39 ± 1.6 NVS units on terms of life quality improvement and pain relief (= 0.000) .Overall mobility improved in 18/18 (100%) patients.There were no clinically significant complications noted in our study. During the follow-up period , all patients underwent a mean of 1.3 sessions for facet joint  and nervAccording to IBM SPSS Sample Power 3, the statistical power of our study is 100%.de novo) degenerative scoliosis involves spinal deformity that develops and becomes symptomatic after skeletal maturity of the patient is complete and finally secondary degenerative scoliosis due to miscellaneous causes including trauma and vertebral fractures, osteoporosis, and other metabolic bone diseases and iatrogenic causes [ Adult scoliosis is an important and common causative agent of severe debilitating back pain affecting the quality of life and physical function of 1.4–12% of population worldwide and 6% of the population over the age of 50 years –22. Primc causes . Pathophc causes –29.  The most commonly reported symptoms include back pain, pain localised on the curve's apex or concavity and on the facet joints, sagittal imbalance, sciatica related to nerve root compression usually at the bottom of the curve, and claudication due to spinal central or recess stenosis , 22, 25. The decision for treating or not adult degenerative scoliosis and by what means is a complex one based upon many factors including patient's age, general health condition, and expectations as well as bone quality. Patients requiring treatment seem to constitute less than 1% of the screened population and less than 10% of those with curves greater than 10° , 31. How The long-term outcomes, complications, and occasionally suboptimal results which accompany open surgery in adult degenerative scoliosis have led to the development of other treatment techniques that avoid an open surgery. Percutaneous vertebroplasty is a minimally invasive, image guided therapeutic technique which through direct usually transpedicular approach to the vertebral body uses acrylic cement (polymethylmethacrylate—PMMA) for pain reduction, mobility improvement, and stabilization of the vertebral column . PMMA is MR scans with STIR  sequences are very sensitive on illustrating bone oedema and played a pivotal role in patient inclusion in our study. As in the cases of arthritis and leukemia, pain due to bone edema can be attributed to a variety of factors including trabecular microfractures , 40. ProScoliotic spine looks like an arch and theoretically can be divided in three parts: outer, middle, and inner part. Any arch is principally balanced by two types of forces, compression forces and distraction forces. Geometrically, it is an established fact that for an arch to be mechanically stable and sustain weight the line of force between various parts of the arch  must pass through the middle section. In the MRI of a scoliotic spine, bone edema lies in the middle and inner part of the curvature (imaging finding seen in the vast majority of the patients included in our study). Potential explanations for this include loading of the middle part (scoliosis' line of force) and trabecular microfractures (occurring either due to excess loading or due to microtraumas when subsequent vertebrae come close together). Since the maximum loading occurs in the middle and concave (inner) part of scoliosis, another potential explanation for bone edema might be that this is an expression of an elevated bone metabolism (remodelling). No doubt, as it is shown from our study, the pathophysiologic multicomponent of adult degenerative scoliosis requires combined therapies as well. Therefore, percutaneous vertebroplasty is performed for the pain due to bone insufficiency/edema/microfractures and is combined with percutaneous infiltrations for facet joint syndrome or neuralgia. In any case neurologic deficit is an emergency requiring surgical treatment, and vertebroplasty with or without infiltrations should be reserved for the rest of the cases. Clinical examination plays a pivotal role for proper patient selection. Patients with pain exacerbation during percussion of the spinous process should be treated with vertebroplasty. Those with pain exacerbated upon pressure at the level of the facet joint (facet joint syndrome) or upon the level of interspinous ligament (Baastrup disease) or with sciatica or other neuralgias should be directed towards other treatments. Up to our knowledge, this is the first study upon vertebroplasty in adult scoliosis. Limitations of our study include the small number of patients enrolled. Reasons for this include slow recruitment and patients' choice of other treatment regime. Another limitation is the lack of randomized control group for the assessment of vertebroplasty as a therapeutic regime for lumbar scoliosis and the fact that our study is not a prospective one. No doubt, extended studies with larger patient sample are necessary to support and prove these preliminary results.Percutaneous vertebroplasty with PMMA seems to be an effective therapeutic technique for supporting adult degenerative scoliotic spine . It can be proposed as an initial treatment in the scoliosis of the elderly prior to surgery and in combination with conservative treatment methods. Preliminary results report significant pain reduction and mobility improvement but further studies are required.


Several treatments have been suggested in shingles viral infection caused by Varicella zoster virus that may lead to complications such as PHN . Intradermal injection of botulinum toxin was shown with few side effects. This study evaluates the efficacy of intradermal injection of botulinum toxin in patients suffering from PHN.Fifteen patients suffering from PHN for more than1 month were enrolled. Data collected were patients' age, sex, and lesion site, the dermatome involved and the duration and severity of pain by visual analog scale (VAS). Botulinum (15 units /every 10 cm(2) of body involved) was injected intradermally. The patients were followed 2, 14 and 30 days after injection.Of participants, 6 were males and 9 females. The mean age was 60 years and the mean duration of neuralgia was 6.5 months. The mean VAS on day 2 was 6.4, on day 14 was 7.2 and after 30 days was 7.6. The overall pain after injection decreased but was not significant.It seems that intradermal injection of botulinum toxin decreases pain in PHN patients and this decrease is less prominent by passing time. Zona occurs due to weakening of immune system, increase in age, morbidity, chemotherapy, etc. Its prevalence in normal population less than 20 years is 1/1000 and is 5-10 times higher in those above 80 years of age.PHN is divided into three phases of acute (first month after the onset of rash), sub-acute (one to four months after the onset) and chronic (> 4 months after the onset) The painOne of the reasons for the constant pain months after zona infection is the increase in the number of P fibers and decrease in the number of the large nerve fibers which suppress the pain transmission. One of tIn this interventional study, 15 patients suffering from PHN were selected using simple sampling method. The patients were included if they were over 18 years of age, had developed PHN at least one month after the rash, had not used botulinum toxin type A previously, had no coagulopathies and localized infection, no history of allergy to analgesics, did not have any tumor at the site, did not have septicemia, were not pregnant or lactating, did not have psychiatric problems or mental retardation, did not use amino glycosides, and did not suffer from myasthenia gravis.After selection of patients, required explanations regarding the features of the drug, method of injection, possible complications of injection, possible analgesic effects were provided for patients. A consent form was taken from each patient. A questionnaire was used including data on age, sex, address, chief complaint, site of lesions (rash), the dermatome involved, duration of PHN and severity of symptoms determined through a Visual Analogue Scale (VAS) as a standard criteria for determining the severity of pain. The seleBefore starting the intradermal injection of botulinum toxin type A, 2% lidocaine gel was applied on the site. After applying the gel, botulinum toxin A specific for every patient was injected based on our selected pattern. Fifteen units of botulinum toxin A diluted with 2% lidocaine were injected intradermally per 10 cm(2) of the painful surface area using the syringes used for injecting insulin. For patients, botulinum toxin type A with the trade name of dysport was used and each vial of the toxin was diluted with 4 ml of 2% lidocaine. The amount of toxin was different for every patient depending upon the extent and site of the lesion. The patients were followed after 2, 14 and 30 days and the leftover pain was measured using VAS. Injections of the toxin and the follow-ups were done by one person. All data were statistically analyzed using SPSS software . In order to measure the effects of the toxin, Repeated Measure ANOVA was used and 0.05 was considered as the significance level.Out of 15 patients, 6 were male and 9 were female. The minimum age was 50 years and the maximum 67 years with the mean of 60 years. The minimum duration of PHN was 1 month and the maximum was 36 months with the mean value and standard deviation of 6.4±8.4. The dermatomes involved ranged from 2-7 with a mean of 4 dermatomes. VAS was measured during the follow-up visits of the patients. On day 2, VAS was between 0-10 with the standard deviation of 6.4±4.4. In the second week, it was measured to be between 0-10 with the standard deviation of 4.2±7.2. Similarly, VAS was measured in the fourth week with minimum and maximum values of 0-10 and standard deviation of 3.7±7.6.The pain caused by PHN has a very complex mechanism, so different treatments have been suggested including routine analgesics, tricyclic antidepressants, carbamazepine, gabapantine, perfenazine, haloperidol, phenophenazine, aspirin, narcotics, cognitive techniques like relaxation, hypnotism and bio feedbacks, and invasive techniques like surgery .14]15] [15] 14][ [15] 14]After reactivation, zona causes inflammation of the posterior ganglionic roots along with changes in the nociceptive pathways with automatic discharges and decrease in the nerve transmission which leads to the neuropathic pain. On the other hand, the nervous system becomes very sensitive to pain and develops pain even when in contact with weak stimuli.29]30][[30][29][[[30][29]of the efferent fibers A-beta after the neuronal damage causes pain upon touch, and presynaptic afferent fibers C causes automatic pain. The mechanism of allodynia is not clearly known yet. IntraderIntradermal injection of botulinum decreases the substances with nociceptive sensitivity. Studies have shown that nociceptive effect of the localized injection of botulinum toxin leads to the inhibition of the release of formalin-induced glutamate, P substance and calcitonin gene-related peptide which play an important role in the inflammation of neurons.28] On t On t28] A study was done on an 80 year old male suffering from PHN, who had co-morbidities like coronary heart disease and heart failure. The oral medications given to the patient were not effective as they caused delirium and cognitive dysfunction. Intradermal botulinum injections were given which were very effective as they decreased the pain of the patient from VAS=10 to VAS=1 and the analgesic effect of the injection lasted for 52 days.Another study done on 3 patients suffering from PHN showed that botulinum injections decreased VAS from 8 to 2 in the second week of the follow up. In the tenth week, pain increased as compared to the second week but it was bearable. SimilarlConsidering the present and some previous studies done on the effect of botulinum toxin in patients suffering from PHN, it seems that there can be a decrease in pain in the first week. However, analgesic effects of botulinum toxin decrease gradually as the weeks pass by. Overall, the pain is less and more tolerable when compared to pre-treatment period. This problem was reported in all studies. Due to the low number of available eligible patients, control group was not included in this study and it is suggested that a random clinical trial should be performed in which a group of patients receive placebo so that the analgesic effects of botulinum in the treatment of PHN can be better evaluated.