Pancreatic cancer is devastating due to its poor prognosis. Patients require a multidisciplinary approach to guide available options, mostly palliative because of advanced disease at presentation. Palliation including relief of biliary obstruction, gastric outlet obstruction, and cancer-related pain has become the focus in patients whose cancer is determined to be unresectable. Endoscopic stenting for biliary obstruction is an option for drainage to avoid the complications including jaundice, pruritus, infection, liver dysfunction and eventually failure. Enteral stents can relieve gastric obstruction and allow patients to resume oral intake. Pain is difficult to treat in cancer patients and endoscopic procedures such as pancreatic stenting and celiac plexus neurolysis can provide relief. The objective of endoscopic palliation is to primarily address symptoms as well improve quality of life. Accurate staging requires a multidisciplinary approach including imaging, tumor markers, and if available pathology via surgical exploration, to further classify the cancer's prognosis. Laparoscopic staging to determine resectability and thus prevent unnecessary exploratory laparotomies has had low detection rates and has fallen out of favor . Even wiGiven this poor prognosis, palliation may be the only option and is targeted at the multiple complications that can occur with pancreatic cancer. Improving symptoms, reducing hospitalization, and trying to enhance overall quality of life are amongst the goals of palliation. Palliation not only includes radiation or chemotherapy to reduce tumor burden but also surgical, radiologic, or endoscopic interventions -8.Biliary obstruction, gastric outlet obstruction, and pain due to tumor advancement in adjacent nerve plexus or pancreatic duct involvement are common sequelae of cancer . Endosco2.et al., in a prospective randomized controlled trial, compared patients with metastatic pancreatic cancer with liver metastasis (n = 30) who underwent either endoscopic drainage  or surgical drainage to evaluate to cost and quality of life. The authors found less cost (p = 0.0013) and improved quality of life scores at 30 and 60 days  with endoscopic palliation. Interestingly, no difference was seen in rates of complications, re-admissions for complications or duration of survival [Mass at the head of the pancreas is the most common location for pancreatic cancer, leading to biliary obstruction in 70–90% of patients ,11. Bilisurvival .Several studies have studied quality of life parameters in patients deemed unresectable and with biliary obstruction, and found that biliary stenting can improve their overall well-being . In addi2.1.Prior to endoscopy, appropriate high resolution imaging (CT or Magnetic Resonance Imaging (MRI)) is typically obtained to delineate tumor burden and a reasonable roadmap of the biliary tree. Insertion of a biliary endoprosthesis is performed via endoscopic retrograde cholangiopancreatogram (ERCP) where selective cannulation of the bile duct achieved via a catheter and over a guidewire, a stent is typically advanced through a tight stricture, and deployed across the ampulla and into the duodenum. Biliary stent allows for drainage with subsequent relief of jaundice and pruritus with success rate of insertion at 90–95% in most experienced centers . Endosco2.2.Initially, plastic stents were used for palliation and rapidly gained popularity due to ease of use and relatively low cost. The median patency rates were approximately 3–4 months ,22. The vs. 278 days; p = 0.0004) as well as a higher rate of cholangitis and associated length of hospitalization, with no statistically significant cost difference  [With the evolution of self-expandable metal stents (SEMS) patency length was improved. Using small caliber catheter delivery system (7.5–10 French) accommodating the working channel of the endoscope, the SEMS is deployed across the malignant biliary stricture up to 30 French. The larger diameter allows for enhanced patency, up to 10 months. A meta-analysis comparing plastic to metal biliary stents demonstrated no statistical difference in technical success, therapeutic success, complications, or 30 day mortality but did show a lower risk of biliary obstruction for the latter . Cost efInterestingly and supported by the previous studies, survival was no different and fuels the debate about what stent is most appropriate. Most endoscopists would agree that prognosis plays a large part in this decision, as metal stents provide the most benefit in patients expected to survive at least 4–6 months . The ratvs. 166 days for uncovered stent) [et al. compared uncovered SEMS to partially covered SEMS  in patients with inoperable distal malignant obstruction and found no difference in rate of biliary obstruction (p = 0.53) or patient survival (p = 997), although the partially covered stent was prone to migration (p = 0061) [et al. argues against preoperative biliary decompression using plastic stents [SEMS initially were uncovered and this feature did not make them removable in case of malfunction and allowed for tumor ingrowth and mucosal hyperplasia . These fd stent) . Howeverd stent) ,35. Most = 0061) . It is s = 0061) ,37. One  = 0061) ,38. All  = 0061) . Furtherc stents .3.Gastric outlet obstruction (GOO) is one of the later presentations of pancreatic cancer, occurring in 10–20% of patients, which leads to a mass effect from the pancreatic head obstructing the duodenum ,42. Hist3.1.i.e., oral contrast study).In order to place a stent for relieving an obstruction, the location and the extent of tumor involvement is defined via imaging  and its newer version the Enteral Wallflex (Boston Scientific) for duodenal stenting that can be advanced into the working channel of a standard endoscope . Once th3.2.et al. have one of the largest series of patients with enteral stenting involving 46 patients with reported 100% success rates of SEMS deployment and 91% clinical success rate [et al., which is a major goal of palliation [The success of duodenal stenting are measured by the patient returning to oral intake, with an average rate of 87–100% with minimal complication rates as low as 1.2% . Philipsess rate . Even thess rate . Anotherlliation .4.Pain is a debilitating symptom in pancreatic cancer which severely affects quality of life. Patients with advanced pancreatic cancer can present with severe pain due pancreatic duct obstruction or nerve involvement ,51. One Although much of the data measures outcome in symptom control, there is paucity in data regarding the complication rates  in these patients.Since pain can be related to neural plexus involvement, celiac plexus ablation has been offered. The technique has evolved in the past century to currently include injection of neurolytic agents, such as phenol or alcohol, to treat the visceral afferent pain. Some have also suggested cryotherapy or even excision therapy . The traAlthough not as well studied, several other approaches such as splanchnic neurolysis either via surgical or radiologic approach do exist but require further research of their success rates. Splanchnic neurolysis for instance appears to carry similar risk to celiac plexus neurolysis .4.1.et al. and has since evolved to lead to development of celiac plexus neurolysis (CPN). Both methods are now used via endoscopic ultrasound (EUS) guidance for different purposes; where CPB is mostly used for chronic pancreatitis and CPN for pancreatic cancer pain [et al. described the efficacy of direct injection into the ganglia [Celiac plexus block (CPB) was first described in 1914 by Kappis cer pain . The difcer pain . Once thcer pain . CPN evo ganglia . This te4.2.et al. described EUS-guided CPN on patients with unresectable pancreatic carcinoma and chronic pancreatitis (n = 33). Ninety four percent (16/17) of patients with cancer and 4/5 with chronic pancreatitis reported pain relief. Interestingly, 34% had initial pain exacerbation thought to be related to improved therapeutic response (p < 0.05) [et al. evaluated the use of narcotics post CPN and reported a transient reduction in supplemental narcotic pain management for up to four weeks post procedure then rebounded back to their original pain level if higher doses of opioids were note used. The authors concluded that CPN should be initiated earlier in the course of the pain to prevent the rebound, while the anatomy of the pancreas is still in tact to identify appropriate structures [Multiple studies conclude that both CPB and CPN have a significant palliative role in chronic pancreatic abdominal pain. However, it is important to note that they do not eliminate the use of pre-procedure narcotic pain management. CPB appears to be most effective for chronic pancreatitis pain rather than pancreatic cancer pain as described by a recent meta-analysis . The stu < 0.05) . A few sructures .et al. reported the importance of tumor location in the efficacy of CPN, where patients with malignancy at the body or tail of the pancreas had better pain relief than those with pancreatic head cancer [et al., with hyperalgesia in 9%, postural hypotension in 20% and diarrhea in 7% of the patients, all of which were noted to be transient symptoms [Catalano d cancer . EUS-guisymptoms . The bensymptoms .5.Pancreatic cancer has very poor prognosis and often palliative procedures are the only option for patients to relieve their symptoms and improve their quality of life. Patients benefit from endoscopic approaches to treat biliary obstruction, gastric outlet obstruction, and cancer-related pain. Indication for endoscopic intervention is determined on a number of factors including patients' prognosis and life expectancy.


A randomized trial of Traditional Chinese Medicine (TCM) for temporomandibular joint dysfunction (TMD) showed a linear decline in pain over 16 TCM visits. Here we investigate whether medication increases could account for improvement, or whether pain medications were also reduced.One hundred sixty-eight TMD patients received TCM or enhanced self-care using a stepped-care design where those who failed on self-care were offered TCM. This report includes 121 patients during their first 16 TCM visits. The initial 8 occurred more often than weekly; patients and practitioners determined subsequent schedules. Outcome data were collected via study-administered questionnaires at standard times, and self-report at every treatment visit. Here we report on average pain (VAS 0-10) and pain medications over the previous week, collected at treatment visits. We converted pain medication intake to equivalent weekly doses of aspirin (for NSAIDs and acetaminophen) or morphine (7.5mg for narcotics). Pain was analyzed by linear regression with random effects for within-individual correlations. Medication use was log-transformed and analyzed using quadratic splines.The sample was 85% female and on average 44 (SD=13) years old. Narcotics users’ (n=32) average pain improved -2.56 units over 16 visits (p<0.001). Narcotics use declined until visit 11 , and then increased to week 16 . NSAID use declined linearly (p=0.019), -0.47 and -0.20 doses/wk over visits 1-11 and 11-16, respectively. For the 18 participants in the top quartile of NSAIDS-only users, average pain decreased linearly over 16 visits . Dose of NSAIDs declined between visits 1-7  and increased between visits 7-16 . NSAID use among the rest remained low and stable.Among patients using narcotics and those who had the highest NSAID intakes, we observed a short-term reduction in medication use that was partially sustained as TCM visits became less frequent.


Several studies have investigated outcomes after disc surgery. However, the occurrence of kinesiophobia has not been investigated previously in patients after disc herniation surgery. In this cross-sectional study, we investigated kinesiophobia in patients who had been treated surgically for lumbar disc herniation, and we related the results to established outcome measures. 10–34 months after surgery, questionnaires were sent to 97 patients who had undergone standardized open discectomy. Outcome measures included Tampa scale for kinesiophobia (TSK); Oswestry disability index (ODI); European quality of life in 5 dimensions (EQ-5D); visual analog scale (VAS) for leg and back pain, work disability, and patient satisfaction; Zung self-rating depression scale (ZDS); pain catastrophizing scale (PCS); and a self-efficacy scale (SES). 36 of 80 patients reported having kinesiophobia. There were statistically significant differences in ODI, EQ-5D, VAS leg and back pain, ZDS, PCS, and SES between patients with and without kinesiophobia. Half of the patients suffered from kinesiophobia 10–34 months after surgery for disc herniation. These patients were more disabled, had more pain, more catastrophizing thoughts, more symptoms of depression, lower self-efficacy, and poorer health-related quality of life than patients without kinesiophobia. Numerous studies have investigated outcomes after disc surgery and found poor results in 10–35% of the patients, depending on what outcome measure was used . In a suIn addition, affective factors, particularly fear, have proven to be central in explaining and in understanding of persistent musculoskeletal pain. 3 terms are used to describe fear in relation to pain: pain-related fear, fear of movement, and kinesiophobia. Pain-related fear is a broad and general term that covers all kinds of fears related to pain . Fear ofKinesiophobia is considered to play a negative role in the outcome of rehabilitation for patients with low back pain, and a high prevalence of kinesiophobia has been observed in patients with persistent low back pain . Since pThe present study had a cross-sectional design. The regional ethics review board approved the study (number Ö 246-03). All 97 patients between 18 and 65 years of age who had undergone standardized open discectomy during 2004 and 2005 in Södra Älvsborgs Hospital (Sweden) were invited to participate in the study. Discectomy was offered to patients with severe leg pain that had not resolved after at least 6 weeks, if CT or MRI showed disc herniation that would explain the clinical findings. After surgery, the patients were recommended to exercise according to an early, active rehabilitation program . QuestioThe descriptive data included age, sex, duration of pain before surgery, and history of previous disc herniation surgery.The Tampa scale for kinesiophobia (TSK) questionnaire comprises 17 items scoring the subjective rating of kinesiophobia. The score varies between 17 and 68, and The Oswestry disability index (ODI) comprises 10 items assessing back-specific function . The totindex and EQ-5DVAS. EQ-5Dindex ranges from –0.59 to 1.0 where 1.0 is optimal health. The mean EQ-5Dindex is 0.86 for a Swedish population aged 40–49 years old (VAS) ranges from 0  to 100 .The European quality of life in 5 dimensions questionnaire (EQ-5D) was used for measurement of health-related quality of life (HRQoL) . The EQ-ears old ; therefoPain intensity was rated on 2 visual analog scales (VAS), 1 for leg pain and 1 for back pain . The VASWork status was measured using a 3-grade Likert scale: working full-time, full-time sick leave, and part-time sick leave.Patient satisfaction with treatment was measured on a 3-grade Likert scale: satisfied, less satisfied, and dissatisfied .The Zung self-rating depression scale (ZDS) scores depressive features on a scale from 20 to 80 . The morThe Pain catastrophizing scale (PCS) scores catastrophizing thoughts on a scale from 0 to 52 . PatientThe self-efficacy scale (SES) assesses functional self-efficacy beliefs specifically related to various basic physical activities . The totResults are presented as median values and range, except for age, which is presented in mean (SD). Statistical comparisons between those with and without kinesiophobia were made from logistic regression with adjustment for age and sex. Comparison without adjustment was calculated with the chi-square test, with pooling of categories when necessary. The significance level was set at 5%. Statistical analyses were carried out using SPSS software version 18.For 5 patients, 1 TSK item was missing and we used imputation with linear regression to replace the lost information. The imputation technique used may lead to an underestimation of the variance, but the small number of imputed data made this a minor problem. The ODI score was calculated as the sum of the ODI items divided by the number of valid items. In 4 patients, 1 item was missing.26 of 84 patients reported co-morbidity involving a variety of different diseases and illnesses . 13 pati80 patients answered the Tampa scale for kinesiophobia (TSK). Approximately half of them (36/80) reported kinesiophobia scores of > 37 on the TSK . DescripPatients with kinesiophobia showed statistically significantly poorer results in 8 of 10 outcome measures in comparison to those without kinesiophobia  and 3.In ODI, 45 of 79 patients had minimal or no disability (0–20%). Of those, 14 reported kinesiophobia. 18 of the 79 patients had severe disability (> 40) in ODI, and 15 of the 18 reported kinesiophobia.12 of 78 patients reported normal HRQoL (≥ 0.86 on EQ-5D), with 2 patients reporting kinesiophobia.39 of 79 patients had no leg pain. 14 of those 39 had kinesiophobia. 23 patients had no back pain, and 4 of them had kinesiophobia. 19 patients had neither leg pain nor back pain, but 4 of them had kinesiophobia.45 of 74 patients who answered ZDS reported having symptoms of depression; 25 of them reported kinesiophobia.30 of 73 patients were non-catastrophizers, 10 of whom reported kinesiophobia. 21 of the 73 patients were catastrophizers, 18 of whom had kinesiophobia.We found that half of the patients suffered from kinesiophobia 10–34 months after surgery for disc herniation. The patients with kinesiophobia were more disabled, had more pain, had more catastrophizing thoughts, had more symptoms of depression, had lower self-efficacy, and had worse HRQoL than patients without kinesiophobia.After discectomy, leg pain is often reduced—as was found also in this study—but almost half of the patients still reported kinesiophobia. One possible explanation for this could be that fear of pain remains, even though the sensory component is gone. Pain-related fear develops if pain is interpreted as threatening . Fear ofIt was surprising that such a high degree of kinesiophobia was reported after surgery despite the patients being recommended exercise according to an early, active rehabilitation program . A recenThe TSK was developed to discriminate between non-excessive fear and phobia in patients with chronic musculoskeletal pain . In the Patients with kinesiophobia had had pain for the same period of time preoperatively as patients without kinesiophobia. Similarly, Patients with a high degree of kinesiophobia also tend to have more depressive symptoms. It is well-known that pain and depression are closely linked. Another study found that more than half of the patients who reported anxiety/depression before surgery still felt the same after being operated . Arpino In summary, we found that patients who reported a high degree of kinesiophobia were also more affected in several other variables. We would argue that kinesiophobia is a factor that should be considered throughout the rehabilitation process.


Various hemostatic and analgesic agents and techniques have been used to reduce intraoperative and postoperative hemorrhage and pain in tonsillectomy.Aims and objective; The current study aimed to compare the effect of using adrenaline plus tramadol and normal saline in maintaining hemostasis and control of pain in cold dissection tonsillectomy.This prospective randomized study was conducted over a period of 10 months in department of otorhinolaryngology state medical college Srinagar. In the current study 46 patients planed for tonsillectomy were put into two groups. 23 patients in each group. In group A patients (study group) 4ml of solution containing 1:200000 adrenaline and 2mg/kg tramadol was injected in peritonsillar space. In group B patients (control group) 4ml of normal saline was injected in peritonsillar space.It was found that the time required to achieve heamostasis and post operative pain was less in group A patients in comparison to Group B patients. There was no significant side effect or complications when adrenaline and tramadol were used.Large randomized controlled studies are needed to compare tramadol plus adrenaline infiltration with other heamostatic and analgesics, but the current study indicated that Tramadol plus adrenaline infiltration could be an effective method to reduce the post operative pain , operative time and time to achieve heamostasis in tonsillectomy surgeries. Therefore the use of Tramadol plus adrenaline infiltration should be further promoted and implemented as routine use in tonsillectomy surgeries. Tonsillectomy with or without adenoid- ectomy is one of the most frequent performed procedures in ENT departments. Frequently, tonsillectomies are associated with significant periop-erative bleeding and postoperative pain . PeritonHemorrhage is one of the most important complications of tonsillectomy which could be primary, reactionary or secondary. To avoid this complication, proper preoperative preparation of patients is essential by proper history taking, clinical examination and investigations to rule out bleeding disorders in patients and to ensure that patients are optimized for the procedure.Controversies exist in the preoperative evaluation of patients for tonsillectomy especially regarding hemorrhage and its control  but this paper would not dwell on these issues.The most important primary cause for morbidity following tonsillectomy in early postoperative period is Pain. This results in decrease of oral intake, dehydration and also prolonged hospitalisation. Various methods of decreasing postoperative pain have been devised. Boliston and Upton showed tTramadol is a centrally-acting drug, which is effective in the treatment of moderate to severe pain . In addiThe current study aimed to evaluate the effect of peritonsillar infiltration when performed with one of the two different solution  upon time reduction in achieving complete heamostasis and postoperative pain levelsAfter Institutional Ethics Committee approval and written informed consent was obtained from patients and/or their parents, 46 patients aged between 10 and 24 years, of ASA 1–2 status undergoing elective tonsillectomy were enrolled in a randomized double blind study. Patients having cardiac, pulmonary, hematologic or hepatic diseases, or known allergy to administered drugs, and the ones who had received any analgesic drug in the last 24 h were excluded from the study.All procedures were performed under general anesthesia by a standard anesthetic protocol. Anesthesia was induced with 2 mg kg _1 propofol intravenously . After having an i.v. line inserted on the dorsum of the hand, infusion of the lactated ringer’s solution started. Following muscle relaxation with atracurium and tracheal intubation, anesthesia was maintained with isoflurane 2–3% and 50% nitrous oxide in oxygen. After the induction i.v paracetamol 5 mg kg _1 were given as infusion to all patients. After the proper positioning, children were randomly allocated into two groups using a shuffled, sealed, opaque and numbered envelopes to receive 8ml of tramadol plus 1:200000 adrenaline , or 8 ml of saline  preinsicionally. The trial was undertaken in a double blind manner, neither patients nor parents and the surgeons were aware of the injected drugs. The drugs were prepared into the injector making totally 8 ml by the anesthesiologist who was not included in the peri and postoperative evaluation and the injections were performed by the two senior surgeons each were blinded to the injected drug with 23 G needle using aspiration-injection technique. A total of 8 ml, 4 ml for each tonsil was injected into the pericapsular plane as follows: 1.5 ml into the superior pole, 1 ml in between and 1.5 ml into the lower pole. The operation was started with Mucosal incisions performed with cold knife and for tonsillectomy blunt dissection technical was used. Hemostasis was achieved by bi-polar cauterization. After removing the first tonsil a saline soaked gauze applied to surgical field. After removing the second tonsil, hemostasis was achieved by bipolar cauterization if needed. At the end of the surgery , number of the cautery used, time to achieve hemostasis (time registered use of swabs and diathermy), and operation duration was measured. All patients were reversed from anaesthesia using 0.02 mg kg _1 atropin and 0.05 mg kg _1 neostigmine. After the airway reflexes were secured patients were extubated and the children were transferred to PACU(post Anaesthesia care unit) for 30 min follow up.All patients were instructed preoperatively to use 100 mm Visual Analogue Scale (VAS) for pain (0 = no pain to 100 = the worst pain). The pain assessments started after 30 mins of operation and continued in the ward every hour for 6 hours postoperatively.Postoperative supplementary analgesic was available to the patients in the form of inj diclofenac 1.5mg per kg was administered i.m if the recorded VAS score was 50 or greater. Bearable pain period of time was considered as the time from full recovery to the first requirement of diclofenac. The total diclofenac in mg per kg consumption during the first 6 hours was recorded. No other analgesics were administered.The occurrence of side effects such as hypotension, bradycardia, nausea, vomiting, sedation, or other side effects was recorded for each patient at the same timepoints as defined for VAS assessment.A total of 46 patients completed the study. Demographic data  of all subjects were similar in both groups . Time required for hemostasis, the number of cautery used for hemostasis and operation duration were significantly lower in group A compared to group B (P<0.001), . Post opASA (American society of anaesthesio-logists) classification of physical status.There were no significant side effects such as hypotension, bradycardia, nausea, vomiting, sedation, or other side effects in study group in comparison to control group.Postoperative pain and its sequelae are amongst universal complaints of the patients, and post-tonsillectomy pain remains a considerable clinical problem.The current study showed that pre-tonsillectomy infiltration of tramadol 2 mg× kg- (4 ml per tonsil); containing 1/200,000 adrenalin, reduces immediate postoperative pain in patients compared with placebo.The findings are in agreement with results from a previous study , where pTramadol was thought to produce its antinoceptive and analgesic effects through spinal and supraspinal sites rather than via a local anesthetic action. However, several clinical studies have shown that tramadol might have peripheral local anesthetic effect ,12. By dIn the present study, tramadol had a local anesthetic action similar to that of lidocaine, and because of its antinociceptive effect, it could extend the postoperative pain-free period.When extracellular sodium concentration decreases, the nerve fiber becomes sensitive to local anesthetics . Jou et Akbay et al, studied the effects of topical tramadol on postoperative pain and morbidity in children undergoing tonsillec- tomy , and conIn another study to investigate the efficacy of intramuscular injection and peritonsillar infiltration of tramadol to prevent pain in children undergoing tonsillectomy , it was Nausea and vomiting have been major side effects of tramadol used as postoperative analgesia. The incidence of these side effects seems to be mainly related to the peak serum concentrations, an initial IV loading dose of 3 mg/kg caused more symptoms than a subsequent infusion or patient-controlled analgesia .In a study comparing the postoperative analgesic efficacy and side effects of IV tramadol with peritonsillar infiltration of tramadol in children undergoing adenotonsi- llectomy , it has Although the conventional techniques to secure hemostasis like ligation and/or cauterization control the major bleeders yet occasionally the diffuse bleeding and capillary oozing may pose difficulty for the surgeon to locate the bleeders, contribute to inefficient hemostasis and in turn enhance blood loss and prolong operation time . Adrenaline which is the commonly used topical hemostatic agent in our region is a powerful vaso-constrictor producing retraction of blood vessels in the tonsillar bed. Adrenaline also promotes platelet aggregation in the formation of blood clot and has been demonstrated by Hatton to be inexpensive, posing little risk, and decreasing intraoperative bleeding, therefore can be taken as a reasonable hemostatic agent .These characteristics especially the decrease in intraoperative bleeding and invariably decrease in intraoperative time is demonstrated in the current study. Less intra operative bleeding leads to less use of cautery to achieve heamostasis and it added to comparatively less post operative pain in groupA patients in the current study.Large randomized controlled studies are needed to compare tramadol plus adrenaline infiltration with other heamostatic and analgesics, but the current study indicated that Tramadol plus adrenaline infiltration could be an effective method to reduce the post operative pain , operative time and time to achieve heamostasis in tonsillectomy surgeries. Therefore the use of Tramadol plus adrenaline infiltration should be further promoted and implemented as routine use in tonsillectomy surgeries.


Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity.Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants.TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia  compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration.TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks. Idiopathic trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by recurring highly intense electric shock-like pain in the distribution of one or more branches of the trigeminal nerve. The pain is usually unilateral, occurring either spontaneously or precipitated by innocuous sensory stimuli and movements. Although some sensory abnormalities have been reported in TN using detailed quantitative sensory testing Many theories have been proposed to explain the unique pain characteristics of idiopathic TN. In general, theories of TN focus on either central or peripheral nervous system pathogenesis e.g., thalamus, primary and secondary somatosensory cortex , amygdala, anterior and mid-cingulate cortex , insula and prefrontal cortex (PFC), (ii) decreases in areas associated with pain modulation ), (iii) increases in motor regions , basal ganglia), and (iv) abnormalities that progress due to pain chronicity.Patients with chronic pains other than TN can show abnormal gray matter (GM) in brain regions associated with pain and its modulation, sensory-discriminative and cognitive-affective dimensions of pain, emotion, and motor function The University Health Network Research Ethics Board approved this retrospective study of idiopathic TN patients. There was no active participation in this study by patients, as patient data were analyzed retrospectively. Additionally our Research Ethics Board provides study approval, but does not require individual patient consent for retrospective studies. All scans were anonymized prior to analysis and stored in secure databases. Recruitment of healthy control subjects and the procedure whereby their consent was obtained was also approved by the University Health Network Research Ethics Board. Each healthy control participant provided written informed consent.p = 0.81, see results). At the individual level, all but 2 control participants were within 3 years of the patients.Twenty-four right-handed idiopathic TN patients from the Toronto Western Hospital seen between May 2008 and February 2011 were included in the study. Inclusion criteria were: (1) unilateral (right-sided) pain involving at least the maxillary or mandibular (V2 or V3) branches of the trigeminal nerve, (2) intense, sharp, superficial or stabbing paroxysmal facial pain precipitated from trigger areas or by trigger factors; stereotyped attacks for each patient; no clinically evident neurological or sensory deficit or not attributed to another disorder 3 voxels derived from a 256×256 matrix and field of view of 24 cm (controls) or 22 cm (patients), echo time = 5 ms, repetition time = 12 ms, inversion time = 300 ms).Brain imaging data were acquired using a 3T GE Signa HDx MRI system fitted with an eight-channel phased array head coil. T1-weighted 3D FSPGR axial images were obtained from the top of the head to the upper cervical levels of C1–C2 (0.9×0.9×1.0 mmhttp://surfer.nmr.mgh.harvard.edu/); methods have been described in detail elsewhere p<0.05  (http://afni.nimh.nih.gov/afni), as done previously To examine cortical GM, cortical thickness analysis (CTA) was performed using FreeSurfer software v. 4.5.0 (http://www.fmrib.ox.ac.uk/fsl/). Non-brain tissues were removed from structural images using the Brain Extraction Tool (BET) p<0.05 using Randomise, implemented in FSL, corrected for multiple comparisons with threshold-free cluster enhancement http://www.bioimagesuite.org/Mni2Tal/).To examine subcortical GM group differences, we used voxel-based morphometry (VBM) We performed a secondary analysis to determine if prolonged nociceptive activity  was related to GM changes. In this analysis, TN duration was treated as a regressor of interest. Analyses were restricted to the CTA and VBM masks described above. The same statistical correction methods were used to determine significant correlations between GM and pain duration.p = 0.81) from the patient group.Patient demographic information is shown in All CTA results are provided in Subcortical regions that had significantly different GM volumes in the TN patients compared to controls are listed in p>0.05).TN pain duration was not significantly related to cortical thickness or subcortical volume for any region within the CTA and VBM masks, nor within areas of GM abnormality when specifically examined  greater GM in the thalamus, contralateral S1 (putative face area), amygdala, FP, PAG, M1, and basal ganglia (including the putamen and NAc), and (2) cortical thinning in the OFC, pgACC, and insula. Abnormalities in these brain regions have been reported in other chronic pain disorders Potential mechanisms underlying MR-detectable GM differences have been broadly divided into two categories: neuronal and non-neuronal mechanisms, including alterations in vasculature, the size or numbers of glia and/or dendritic spines/branches a priori hypothesis, we found that TN patients had more GM in the thalamic nuclei compared to controls. Although we included patients with only right-sided pain, the greater thalamic volume was found bilaterally. This bilateral finding is in line with a previous functional MRI study on TN patients that showed bilateral thalamic activity when unilateral stimuli were used to evoke pain attacks Consistent with our We further observed that TN patients had thinner cortex in the pgACC, aINS, and OFC compared to controls, a finding that has been reported in numerous chronic pain conditions The mechanism of pain-related cortical thinning is not yet established. One possibility, as described in other patient populations, is that there are focal losses of cortical inhibitory interneurons, making these regions hyperactive Interestingly, the FP was thicker in TN patients; a finding also reported in TMD Similar to findings in migraine Consistent with our hypothesis, we report increased GM in motor regions. One characteristic of TN is that normally non-painful movements can elicit attacks of pain, so some patients attempt to restrict facial movements. This restriction has been observed in other facial pains such as TMD Some basal ganglia structures that were larger in TN patients have also been implicated in non-motor functions. For example, evidence suggests a role for the putamen in the sensory aspects of pain Some previous studies of chronic pain have found correlations between pain duration and brain GM Additionally, nearly all of our patients were taking medication for TN, with the most common being the anticonvulsant, carbamazepine. Although the precise impact of these medications on brain morphology is not known, it is possible that they influence structural abnormalities. Future studies are needed to examine the effects of these drugs on brain GM.Taken together, our study demonstrates for the first time, that patients with idiopathic TN have prominent GM abnormalities in brain regions involved in sensory-discriminative and cognitive-affective dimensions of pain, pain modulation, and motor function. Unlike other facial pains, TN patients have paroxysmal pain, frequently triggered by innocuous stimuli, and are without major sensory loss. The GM abnormalities reported in the current study likely reflect this unique symptomology. Understanding the contribution of central GM abnormalities in this population is a crucial step towards elucidating the mechanisms underlying this unique neuropathic pain.


In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.n = 74); SC placebo at baseline plus oral indomethacin as above (n = 76); or SC rilonacept 320 mg at baseline plus oral placebo (n = 75). The primary efficacy endpoint was change in pain in the index joint ) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (P < 0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55 ± 0.92) relative to indomethacin alone (-1.40 ± 0.96), the difference was not statistically significant (P = 0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69 ± 0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean ± SD age of 50.3 ± 10.6 years. All treatment groups reported within-group pain reductions from baseline (Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.NCT00855920.ClinicalTrials.gov registration number  A cardinal clinical feature of gout is recurrent acute inflammatory flares (acute gout flares) that result in debilitating joint pain and swelling. Gouty arthritis is mediated by monosodium urate monohydrate crystal deposition in and around the joint space due to hyperuricemia. Acute gout flares can be precipitated by a variety of factors including joint trauma, and putative remodeling of articular crystal deposits due to changes in serum urate concentrations, such as during the early months of initiation of uric acid-lowering therapy (ULT) ,2.The incidence and prevalence of gout are increasing, partly as a consequence of increased prevalence of comorbidities such as metabolic syndrome, type II diabetes, obesity, hypertension, and chronic kidney disease ,4. Gout Because of their anti-inflammatory and analgesic characteristics, non-steroidal anti-inflammatory drugs (NSAIDs) are often used as first-line therapy for the treatment of acute gout flares ,11. ColcIL-1β is a major mediator of gouty inflammation and pain , and is Rilonacept is a fully-human, recombinant, soluble decoy receptor protein engineered from human IL-1 receptors and IgG1Fc that binds IL-1α and IL-1β, thus preventing their activation of cell surface receptors . Since rThis phase 3, randomized, double blind, double-dummy, active- and placebo-controlled study was conducted at 60 study centers in North America. The study was performed in accordance with the revised Declaration of Helsinki, approval was obtained from the independent ethics committee , and all patients provided written informed consent.The study was open to male and female patients 18 to 70 years of age having a diagnosis of primary gout based on the American Rheumatism Association (1977 ARA preliminary criteria) for the classification of acute arthritis of primary gout . EligiblEligible patients remained in screening and were subsequently randomized to treatment when they presented with an acute flare within 48 hours of pain onset and met the following additional criteria: pain in the gouty index joint of at least moderate severity using a 5-point Likert scale , a score of at least 1 on a scale of 0 to 3 for assessments of swelling and tenderness at the gouty index joint, and presentation of acute gout flare in three joints or fewer. The index joint was defined as the joint that was most painful at the time of randomization.Patients were randomly allocated 1:1:1 to treatment with either SC placebo at baseline plus oral indomethacin 50 mg three times daily for 3 days (and then 25 mg three times daily for up to 9 days); SC rilonacept 320 mg at baseline plus oral indomethacin as above; or SC rilonacept 320 mg at baseline plus oral placebo three times daily for 3 days and then oral placebo three times daily for up to 9 days. Randomization was stratified by baseline pain score  and country. On-site study visits occurred at baseline (day 1), days 4 and 8, and at a safety follow up on day 31.Patient self-assessment of pain and other gout symptoms were recorded using an electronic diary at baseline, 4, 8, 12, and 24 hours, and then daily until the flare ended. Pain was assessed using the 5-point Likert scale and an 11-point numerical rating scale .Based on index joint pain, patients were eligible for rescue medication at two time points. At 24 hours, patients with extreme pain or severe pain that had not decreased from baseline were eligible for rescue medication with blinded indomethacin 50 mg three times daily for 1 day  or blinded placebo rescue in the other two treatment groups receiving indomethacin. At 48 hours patients with either a) extreme pain alone or b) moderate or severe pain and pain reduction from baseline less than 20% were eligible to receive blinded rescue with indomethacin in the rilonacept-only group , or with placebo in the two groups receiving indomethacin; the duration of rescue was determined by the investigator. Patients receiving rescue medication were not required to be withdrawn. For all groups, efficacy data were set to missing after initiation of rescue medication. The last observation carried forward (LOCF) method was used to impute data after rescue medication for the analysis of covariance (ANCOVA) model, used for the primary analysis.The primary efficacy endpoint was the change in patient-reported pain  in the index joint from baseline to the average of the patient-reported pain values at 24 (day 2), 48 (day 3) and 72 hours (day 4) (composite time point). Secondary efficacy endpoints included the change from baseline in patient-reported pain in the index joint at days 2, 3, and 4. Additional exploratory analyses included proportion of patients requiring rescue medication. Blood samples were obtained for analysis of high sensitivity C-reactive protein (hs-CRP), an established marker of inflammation, at baseline and at study visits on days 4, 8, and 31. Safety and tolerability were evaluated based on the incidence of adverse events (AEs) up to and including the safety follow up visit, and the occurrence of clinically significant laboratory findings determined by the investigator.P < 0.05). ANCOVA was used for the sequential testing of endpoints with treatment and baseline pain score strata  and country as fixed effects. The LOCF was used for imputation of missing data, and pain scores obtained after rescue medication were considered missing for the primary efficacy analysis.For this superiority study, a pre-specified step-down sequential testing procedure was used for the primary efficacy endpoint that compared rilonacept alone vs indomethacin alone only if the comparison of rilonacept + indomethacin vs indomethacin alone was statistically significant . The full analysis set included all randomized patients who received any study medication and had at least one post-baseline assessment, and the safety set included all patients who received any study medication.Figure P < 0.0001) and assessed using the Likert scale. However, the mean reduction in pain with rilonacept plus indomethacin, 1.55 points, was not statistically significantly greater than the mean reduction in pain with indomethacin alone, which was 1.40 points  . Similar results were observed with the NRS; significant reductions from baseline were observed in each of the treatment groups (P < 0.0001), with pain reductions of 3.87 in the rilonacept plus indomethacin group, 4.33 in the indomethacin monotherapy group, and 1.81 in the rilonacept monotherapy group , the ad hoc analysis significantly favored indomethacin monotherapy relative to rilonacept monotherapy (P < 0.0001).All treatment groups were observed to have significant reductions in pain from baseline when averaged at 24, 48 and 72 hours  Figure . Since tp Figure . While tP < 0.05).For the secondary endpoints of mean change in pain at 24, 48, and 72 hours Figure , the treThe proportion of patients who reported having taken rescue medication at > 24 to 48 hours in the rilonacept plus indomethacin group (3.0%) was similar to the indomethacin monotherapy group (4.3%).P < 0.0001) and rilonacept monotherapy (P = 0.0142) relative to indomethacin monotherapy.All treatment groups were characterized by a general reduction from baseline in hs-CRP from initiation of treatment to the safety follow up at day 31 Figure . At day Overall, the incidence of AEs was higher in the groups treated with rilonacept relative to indomethacin alone Table ; AEs werWhereas rilonacept has previously demonstrated efficacy in prevention of gout flare during initiation of ULT with allopurinol ,35, the max for rilonacept is approximately 48 to 72 hours. Since the primary endpoint was the change from baseline to the average of the pain assessments at 24, 48 and 72 hours, it is possible that drug concentrations at the gouty joint were insufficient during the majority of the primary endpoint assessment period. Furthermore, the size of rilonacept  may limit the rate of distribution from plasma to target tissues involved in a gout attack. It is possible that, had rilonacept been administered by the intravenous route, higher serum concentrations achieved soon after administration could have driven greater drug penetration to target tissues, and hence, greater efficacy in treating acute gout flares.Several factors may account for the observed results. In this study, rilonacept was administered within 48 hours of onset of an acute gout flare in patients who were already experiencing substantial pain. First, it is possible that rilonacept may have been more effective had it been administered earlier relative to flare onset, since the ability of IL-1 inhibition to effect a reduction in pain by blocking the cascade of downstream inflammatory mediators may depend on the timing of treatment. Results of a clinical trial with colchicine indicated the success of treating acute gout flares within 12 hours of onset [These data appear to contrast with recent clinical trials of another IL-1 inhibitor, canakinumab, which demonstrated that IL-1 inhibition ameliorated inflammation and pain during an ongoing gout flare as compared to low-dose steroid injections ,31. SeveP < 0.05). These reductions likely reflect IL-1 inhibition by rilonacept, and are consistent with those reported for canakinumab in acute gout flares [Given the collective distinctions in study designs, the extent of the intrinsic differences that may have contributed to the differing outcomes between the soluble decoy receptor rilonacept and the monoclonal antibody canakinumab are unclear. Differences in efficacy among agents in another class of anti-cytokine therapy, TNF-α antagonists, have been demonstrated to be related to such factors in arthritic diseases other than gout ,44. It rt flares .Treatment with rilonacept in this clinical setting was generally well-tolerated, with the frequency of withdrawals due to AEs similar across treatment groups. Although the combination therapy group had a higher incidence of serious AEs relative to both of the monotherapy groups, these AEs were not considered related to rilonacept.In conclusion, in contrast with previous studies that have demonstrated efficacy of rilonacept for prevention of acute gout flares in patients initiating ULT, addition of rilonacept to an indomethacin treatment regimen and use of rilonacept alone provided neither significant additional pain relief nor superior pain relief, compared with indomethacin alone over the 72-hour period after treatment initiation in acute gouty arthritis.AE: adverse event; hs-CRP: high sensitivity C-reactive protein; IL-1: interleukin-1; IM: intramuscular; MSU: monosodium urate; NSAID: non-steroidal anti-inflammatory drug; SC: subcutaneous; TNF: tumor necrosis factor; ULT: urate-lowering therapy.RT has consulted for Regeneron, Takeda, Savient, Novartis, Prescription Solutions, Pfizer, Ardea, BioCryst, and Metabolex. HRS has consulted for Regeneron, Novartis, Ardea, Pfizer, Metabolex, and Westward, and has received a grant from Takeda. JC has consulted for Regeneron. HB has been an investigator for Regeneron, Ardea, Novartis, Takeda, Metabolex, and Savient, has consulted for Regeneron, Ardea, Takeda, and Savient, and has spoken for Takeda, and Savient. RE, JW, SK, and SW are employees and stock holders of Regeneron Pharmaceuticals, Inc. Regeneron holds patents related to the content of the manuscript.RT, HRS, RE, JW, SK, SW made substantial contributions to the conception and design of the clinical trial. JC and HB were involved in the acquisition of data. All authors were involved in the analysis and/or interpretation of data. All authors were involved in drafting the manuscript and revising it critically for important intellectual content. All authors read and approved the final manuscript.


Radiation therapy is a well-recognized, effective modality used for palliative care. Most studies completed to date have endpoints of one month or greater after treatment completion. This study analyzed the response rates at different time points during the first month after treatment.From May 2010 to November 2011, 61 patients treated for 74 metastases were included in the study. The end points were defined as the completion of treatment (CT) and d8, d15 and d30 after the completion of treatment. The response rate was measured by the worst pain in the last 24 hours and the administered opioid dose. Patient assessment was performed during consultations and phone appointments.The overall response rate significantly improved from the CT (38%) to d8 (53.8%), d15 (53.8%) and d30 (57.1%) . The improvement peaked at d8. Patients responding to the treatment at d8 had a significative longer pain relapse free survival (PRFS) compared to patients not responding . From the beginning of treatment to the CT and at d8 , d15 and d30, oral morphine equivalent dose (OMED) did not significantly differ. However, the pain decrease did not result in a performance status improvement, which declined over time (p < 0.001).Radiation therapy is an efficient treatment method for providing pain relief. This relief peaked at d8 after treatment, and the response at d8 is predictive of the response at 4 weeks. Pain management alone is not enough to improve performance status; further studies are needed to evaluate a more global supportive care approach. Approximately 50% of patients with cancer present metastases at the initial presentation or at relapse. Bone is one of the most frequent metastasis locations, particularly for lung, breast, and prostate cancers. Pain is the most common and debilitating symptom of bone metastases. Pain alters patient quality of life and requires specific support. This support includes motor function improvement and local or systemic treatment. Treatment may consist of the concomitant or alternate administration of analgesics, chemotherapy, hormone therapy, bisphosphonates, surgery, interventional radiology, and radiotherapy.External beam irradiation for painful bone metastases has been well established by many prospective trials and can lead to pain relief and/or reduce analgesic consumption. Several radiation treatment schedules with similar effectiveness have been described. The most used schedules deliver 30 Gy in 10 fractions of 3 Gy, 20 Gy in 5 fractions of 4 Gy or a single fraction of 8 Gy. An updaThe response to irradiation has been evaluated using many different types of measure. Visual analogue scales, a numeric scale, a Brief Pain Inventory, the dose of analgesics and the requirement for re-irradiation are the most frequently used. FurtherIn this study, we report the response rate at the end of treatment and one, two and four weeks after treatment to determine whether an earlier evaluation could predict a definitive response.From May 2010 to October 2011, patients referred to the radiation department of the Regional Cancer institute Paul Strauss for painful bone metastases were eligible to participate in this study examining the response after irradiation. The inclusion criteria were age above 18, ability to understand and speak French and consent to participate to the study. This study was approved by our institutional review board (committee against pain CLUD). Patients who underwent previous surgery, cementoplasty, or in-field irradiation and remained in pain were also included. Clinical evaluations were performed at the first radiotherapy consultation  and at the completion of treatment (CT). Patients provided informed consent. A visual analogue scale (VAS) strip was given to each patient to evaluate their pain at home after being instructed on how to use it. On days 8, 15 and 30 after the CT, evaluations were performed during a scheduled phone appointment. The interviewer (PT) used a home survey to obtain the patient information.The information collected at the first consultation included age, gender, primary cancer location, pathology, painful bone metastasis location, performance status, steroid treatment, analgesic morphine taken in the last 24 hours converted to the oral morphine equivalent dose (OMED) and local treatments received previously. On d8, The radiotherapy response rates were evaluated using the international bone metastases consensus group (IBMCG) criteria Table .The treatment was performed using linear accelerators with 6 MV or 15 MV photon beams. The TomoTherapy Hi-ART and Novalis TX systems were used for IMRT and SBRT treatment planning. The time period between the first consultation and the first irradiation session did not exceed 2 weeks.2 test. The nonparametric Wilcoxon test was used to compare repeated measures of pain score and OMED. A pain relapse free survival (PRFS) was calculated for the patients responding at every end points from the CT to d30 (range from 0 to 4 weeks). PRFS was analysed using a Kaplan Meyer method. p <0.05 was considered significant. Data were analyzed using SPSS version 20 (IBM Software).The response rates at the different end points were compared for each patient: i) between the BT and CT, BT- d8, BT-d15 and BT-d30, ii) between the CT and d8, CT- d15 and CT-d30 iii) between d8- d15 and d8-d30, iv) between d15 and d30. Only patients with an available response rate at the compared end points were analyzed, and if the information was missing, the patient was excluded from the statistical analysis at the corresponding end point. Responders were patients with a complete response (CR) or a partial response (PR); patients with stable disease (SD), progressive disease (PD) and undetermined responses (UR) were considered as non-responders. The distributions of the Karnofsky performance status (KPS) (< 70% and ≥70%) and World Health Organisation performance status (WHO PS) (<2 and ≥ 2) at each evaluation were analyzed by the χBetween May 2010 and November 2011, 61 patients were enrolled in the study. The general characteristics of the patients are summarized in Table Forty-nine metastatic sites were not treated previously (66%). Twenty five metastases were treated before the present irradiation, within a minimum of one month. Ten metastases (14%) were operated on , 9 (12%) received cementoplasty, 5 (7%) were irradiated, and 1 patient underwent surgery and radiotherapy. The six patients who previously received irradiation presented metastases located in spine for four and in pelvis for two metastases. The irradiation schedules before re-irradiation were 8 Gy in a single fraction (one patient), 24 Gy in 6 fractions of 4 Gy (one patient), 30 Gy in 10 fractions of 3 Gy (two patients), and 36 Gy in 12 fractions of 3 Gy (two patients).Concerning the current irradiation, 66 bone metastases (89%) were treated with 3D conformational radiotherapy. Seven spinal metastases (9.5%) were treated with SBRT (re-irradiation in 4 cases). One metastasis was treated with IMRT. For 62 treatments (91%), the dose schedules were 8 Gy in a single fraction, 20 Gy in 5 fractions of 4 Gy and 30 Gy in 10 fractions of 3 Gy. The SBRT dose was 23.31 Gy in 3 fractions of 7.77 Gy delivered on days 1, 3 and 5. Other fractionations were proposed in 5 patients.p = 0.018), but age, gender, VAS and OMED weren’t statistically different. The response rate to the treatment, median worst pain, median WHO-PS, KPS and OMED are presented in Tables All patients included completed the treatment, and an evaluation at the completion of treatment was performed in 50 patients (82%). On days 8, 15 and 30, evaluations were obtained from 39 64%), 39 (64%), and 42 (69%) patients, respectively. The reasons for no reply included unreachable by phone, death or refusal to continue the study . From the BT to d8, d15 and d30, the VAS decreased to 3 and remained statistically significant . There was no significant difference in the maximal VAS from the CT to d8, d15 or d30 , from d8 to d15 or d30  or from d15 to d30 (p = 0.345).Using the visual scale, the patients had a significant decrease in the median maximal pain from the BT to the CT from VAS 7 to VAS 5, respectively .The OMED did not significantly differ between each interval of evaluation. The mean OMEDs at the BT, the CT, d8, d15 and d30 were 40 mg, 40 mg, 30 mg, 30 mg and 40 mg, respectively , from d8 to d15 and d30 , and from d15 to d30 (p = 0.002). Univariate analysis using Kaplan Meyer method highlighted PRFS for patients having a response at d8 was significantly improved compared to patients not responding: respectively 3,38 weeks vs 0,3 weeks . This result suggests response at d8 is predictive of response at d30.The overall response rates at CT, d8, d15 and d30 were 38%; 53.8%; 53.8% and 57.1% respectively. The CR rates at CT, d8, d15 and d30 were 8%, 10.3%, 15.3% and 16.7% respectively. Using the IBMCG criteria, there were significant improvements  from the CT to d8, d15 and d30 (p < 0.001). However, at d15, the data showed a transitory improvement in WHO-PS and KPS (p < 0.001).Compared to the BT, WHO PS and KPS were significantly decreased at the CT, d8 and d30  at the CT, 9 (15%) patients at d8, 9 (15%) patients at d15 and 9 (15%) patients at d30 Table . AccordiSeveral consensus task forces have attempted to recommend tools or methods for following and evaluating patients with bone metastases,17. One This study showed phone evaluation’s feasibility to assess response to an antalgic irradiation, in order to be able to propose an adequate care of the pain. This method allows the assessment of patients at home, which is more comfortable and avoids travel. Phone evaluations can be performed by a radiation oncologist or a trained nurse. In 2004, a study assessing 830 patients by phone retrieved a higher percent of patients reachable by phone at 4 weeks (57%) after treatment completion with a steady decrease through 12 weeks (48%). Our resal. analyzed 580 patients’ response rates to radiation therapy using pain intensity scale and analgesic consumption[In 2004, Chow and sumption.performance status because many factors contribute to this status. However, one study showed that such patients with a short life expectancy may benefit from analgesic irradiation[Despite the improvement of the overall response to pain after radiation therapy, our study showed a worsening of the performance status. Patients had an altered performance status with a median WHO PS of 2 0–4) at the BT. In several previous studies and trials, most patients had a WHO PS ≥ 2 at the B. Unfortuadiation.This study has some limitations: the population is mixed concerning metastatic localization, performance status, radiation therapy schedule, and radiation technique (RTC 3D or SBRT).The prospective study demonstrated that radiation therapy is a quick and efficient treatment of bone metastasis pain. A phone evaluation of pain relief is feasible in practice. The evaluation of pain at d8 after the CT is predictive of pain relief thereafter. Thus, if needed, treatment decisions can be made earlier in the patient’s disease course. However, a good pain response is not strictly correlated to performance status.VAS: Visual analogue scale; BT: Beginning of treatment; CR: Complete response; CT: Completion of treatment; KPS: Karnofsky performance status; IBMCG: International bone metastases consensus group; IMRT: Intensity-Modulated radiation therapy; OMED: Oral morphine equivalent dose; PD: Progression disease; PR: Partial response; PRFS: Pain relapse free survival; RT: Radiation treatment; SD: Stable disease; SBRT: Stereotactic beam radiation therapy; UR: Undetermined response; WHO PS: World health organisation performance status.The authors declare no conflicts of interest.PT included patients, interviewed patients by phone, conducted statistical analysis, and drafted the manuscript. GN included patients, conceived of the study and participated in its design and coordination and helped to draft the manuscript. DA, MP, JBC, SG, CS included patients. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-684X/12/12/prepub


Objective. The underlying cause for postmastectomy pain syndrome (PMPS) and its impact on quality of life remain unclear. The objective of this study aims to determine retrospectively the prevalence of PMPS, its predicting risk factors, and its impact on quality of life. Method. In this survey, 225 women completed a battery of questionnaires. The questionnaires comprised the short form of the McGill Pain Questionnaire (SF-MPQ) exploring the characteristics and the description of the pain, and a Short Form-36 (SF-36) Health Survey evaluating quality of life. Logistic regression analyses were subsequently performed to identify risk factors for PMPS. Results. 62 women (27.6%) reported PMPS as a consequence of surgery, and the pain was generally mild, mostly localized in breast area and intermittent. The pain was mainly described as aching (62.9%). 144 women reported sensory disturbance. We found that only the younger age is the predictive factor for PMPS (P < 0.05). Compared to the patients who did not experience PMPS, those who suffered from PMPS had significantly worse scores in role limitations due to physical problems , body pain (BP), general health (GH), vitality (VT), role limitations due to emotional problems , and mental health (MH) (P < 0.05). Conclusion. PMPS is a significant problem, and the possible risk factors should be further explored. Patients with PMPS have significant worse quality of life, suggesting that patients should be well informed about the likelihood of experiencing the pain, and they may be afforded greater predictability and higher perceived control to enhance their quality of life. It is reported that postmastectomy pain syndrome (PMPS) is a common problem, ranging from 25% to 60% , 2. The A retrospective questionnaire survey was undertaken on patients who had undergone surgery for breast cancer from Jan 2010 to Dec 2011 in our hospital. Exclusion criteria were non-Chinese patients, benign breast pathology, surgical site infection, or death. The investigation was conducted between Jan 2013 and May 2013. The study was approved by ethics committees of Women's Hospital, School of Medicine, Zhejiang University, before initiating, and all subjects provided verbal informed consent.According to the International Association for the Study of Pain (IASP)  and receThe questionnaires used consisted of two parts. The first part concerning pain characteristics assessment was modulated through the short form of the McGill Pain Questionnaire (SF-MPQ) . The SF-Patients included in this study received a telephone interview to make the oral consent to participate in our questionnaires research. Informed consent was also requested for viewing the patients' medical records on the phone. Then, SF-MPQ with minor modifications and SF-36 (both in Chinese version) were mailed to patients who agreed to take part in the survey, and they were asked to mail back the questionnaires after questions were answered carefully. Those patients who failed to respond within four weeks were contacted by telephone to find out why and, if necessary, mailed the questionnaire again. Eight weeks after sending the first questionnaires, the investigation was closed.Patients' demographic and disease-related data were retrieved from the hospital and department database to identify possible risk factors contributing to chronic pain development. The data included age, BMI, presence of diabetes mellitus and hypertension, type of surgery, surgical complication , preoperative and postoperative adjuvant therapies that included radiation therapy, chemotherapy, and hormonal therapy.t-test with normal distribution and by the Mann-Whitney U test for variables with nonnormal distribution. The Chi-square test was used to compare groups with categorical variables. P value less than 0.05 was considered significant. Univariate analyses and multiple forward stepwise logistic regression analyses were performed to identify risk factors predicting PMPS. After univariate analyses, variables with P value less than 0.05 were included in a multivariate logistic regression analysis to identify independent factors of PMPS.Data was analyzed using SPSS 16.0 software . Continuous variables were presented as mean ± standard deviations, and categorical data were shown as numbers and percentages. Comparison of continuous data was performed by Student's 349 patients were contacted through the phone, and 97 patients refused to participate. Among all these 252 returned mails, 27 patients returned the questionnaire but did not fill in the part of the questionnaire concerning pain or quality of life and were excluded from the analysis. Ultimately, we investigated and analyzed data from 225 patients.2 . Some of the patients were suffering from concomitant diseases: 49 (21.8%) were affected by hypertension, and 12 (5.3%) used oral antidiabetic drugs.225 questionnaires and their medical record were evaluable. Results showed that the average age was 53 years  and average BMI of 23 kg/mn = 14, 22.6%), intermittent pain , and continuous pain . It was also shown that the specific location of pain could be chosen more than once, and the majority of patients chose the breast area and, secondly, the scar. A detailed description of the pain characteristics was shown in 62 patients (27.6% of 225 patients) reported pain as a consequence of treatment. 50 patients (80.6% of 62 patients) reported mild pain, 10 patients (16.1%) developed moderate pain, and 2 patients (3.2%) developed severe pain. Of all the patients who developed pain, only 3 patients (4.8%) had taken oral analgesics. 35.5% experienced pain a few days after surgery, 25.8% patients developed pain a few weeks later, and 38.7% reported that pain started a few months later. Patients described frequency of pain following surgery: transient pain , followed by arm , breast area , and the scar . The most frequently described terms over the affected area were numbness , pins-and-needles , and loss of sensation . A total of 47 women (32.6%) reporting sensory disturbances suffered pain as well compared with 97 (67.4%) reporting no pain, indicating that sensory disturbances may be an increased risk of chronic pain (P = 0.023). This strong association was not attributed to other variables on multivariate analysis.A total of 144 women (64%) reported sensory disturbances or discomfort after surgery. As shown in P < 0.05).In order to assess the impacts of PMPS on quality of life in detail, SF-36 Health Survey was used. As shown in P < 0.05), which implied that younger women tended to develop more pain after surgery.No significant association with the report of persistent pain was found in BMI (data not shown), type of surgery, and perioperative adjuvant therapy  between PMPS attracted considerable attention recently, but there is no agreement regarding the prevalence and risk factors. The aim of this retrospective study was to show the prevalence of PMPS in Zhejiang province of China. The result revealed that the incidence of PMPS was 27.6%, which was similar to recent studies . AlthougThe reported prevalence of PTPS varied from 25% to 60% , 2. ThisAlthough prevalence of PMPS is high, this situation is rarely reported in our country, and it is still considered to be relatively uncommon. One explanation is that breast cancer is a potentially life threatening disease, then clinicians and patients mainly focus on the treatments while disregarding the PMPS. Furthermore, very few patients take the oral analgesia, although an increasing number of breast cancer survivors experience pain. This implied that doctors should follow up patients with emphasis not only on long and effective observation of the treatment, but also on noting any problems advent such as the pain during treatment to enhance the patients' quality of life. The pathogenic mechanisms of PMPS are multifactorial including tissue injury, nerve damage related to surgical procedures, and neuroma pain. Different types of sensory disturbances  are sequelae to surgery and may be an important part of the pain characteristics , 13.Risk factors for the development of PMPS can be related to the patient or the surgery itself. Among patient-related factors, we find that the younger age was shown to be a predictive factor for the development of PMPS, and our results are consistent with previous literature , 14, 15.In recent studies, axillary dissection (not the mastectomy or quadrantectomy) has been demonstrated to be a risk factor for persistent pain after treatment and sensory disturbances compared with sentinel lymph node biopsy , 7, 17. Adjuvant radiotherapy has also been identified as a risk factor for the pain , 19, butBased on SF-36 scores, our study has found that patients' subjective reports of pain were significantly related to quality of life. Women with PMPS had lower SF-36 scores across all health domains, except for physical function and social function, than women who did not develop pain. Our results suggested that in patients who suffer pain after surgery, psychophysical adaptation was decreased compared to patients without pain, which was consistent with previous findings , 24.PMPS is a common complication following breast surgery, which could significantly impact patient's daily life in a negative way. Our study has demonstrated that younger age is an independent risk factor for PMPS. More detailed prospective studies are required to identify the risk factors of PMPS and to plan possible prevention. Meantime, surgeons should keep good communication with patients who underwent breast surgery on the possibility of developing chronic pain to help them alleviate the distress.


Pain is one of the most frequent problems among patients diagnosed with cancer. Despite the availability of effective pharmacological treatments, this group of patients often receives less than optimal treatment. Research into nurses' pain management highlights certain factors, such as lack of knowledge and attitudes and inadequate procedures for systematic pain assessment, as common barriers to effective pain management. However, educational interventions targeting nurses' pain management have shown promise. As cancer-related pain is also known to have a negative effect on vital aspects of the patient's life, as well as being commonly associated with problems such as sleep, fatigue, depression and anxiety, further development of knowledge within this area is warranted.A quasi-experimental study design will be used to investigate whether the implementation of guidelines for systematic daily pain assessments following a theory-based educational intervention will result in an improvement in knowledge and attitude among nurses. A further aim is to investigate whether the intervention that targets nurses' behaviour will improve hospital patients' perception of pain. Data regarding nurses' knowledge and attitudes to pain (primary outcome), patient perception regarding pain (secondary outcome), together with socio-demographic variables, will be collected at baseline and at four weeks and 12 weeks following the intervention.Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential complex intervention." To be able to change and improve clinical practice thus requires multiple points of attack appropriate to meet complex challenges. Consequently, we expect the theory-based intervention used in our quasi-experimental study to improve care as well as quality of life for this group of patients and we also envisage that evidence-based guidelines targeting this patient group's pain will be implemented more widely.NCT01313234ClinicalTrials.gov  Pain is one of the most common problems among patients suffering from cancer . DespiteStudies investigating barriers to adequate pain management among registered nurses (RN) have identified lack of knowledge of cancer-related pain and pain treatment ,12 as a per se is not an effective and viable strategy for changing behaviour. Instead, interactive learning in small groups and learning from personal experience have proved to be winning blueprints for change [Attitudes to and knowledge of pain and its treatment can be improved by means of educational interventions ,18, and r change . To succOur review of the literature has highlighted the importance of a change in nursing practice, but also in attitudes and knowledge among RNs about cancer-related pain management in general. To improve the quality of care in this group of patients further investigations into this complex of problems are thus warranted.1) Will an intervention consisting of the implementation of guidelines on daily systematic pain assessment following a theory-based education, targeting cancer-related pain and pain treatment, lead to a significantly positive improvement in RNs' knowledge and attitudes regarding their pain management?2). Will the interventions targeting RNs influence hospital patients' perception of their cancer-related pain?This study will be carried out with a quasi-experimental design with non-equivalent control groups Figure . Our ratParticipants (i.e. patients and RNs) will be recruited from two surgical wards specialising in patients with a cancer diagnosis at a hospital in South East Sweden. The hospital has 370 beds and provides services for approximately 150,000 people in the region. The intervention and control ward (26 beds on each ward) has 70 RNs and each year the wards admit around 820 patients who have been diagnosed with cancer.Following negotiations on all organisational levels, both wards have agreed to participate in the study. The reason for this optimal numbers of participating RNs (n = 70) is that this study is seen within the organisation as providing support to the staff's annual education slots but also as part of supporting quality assurance of its care provision. Assignment to either the intervention ward or control ward is done by the research team.Sample size calculations for the primary outcome measured by the Knowledge and Attitudes Survey Regarding Pain (KAS) are based on an expected 4.8 change in scores  among thWe will include all RNs on the control ward and intervention ward in accordance with what is stated above. We will include patients with a cancer diagnosis who are aged 18 years and older and who are cognitively intact and able to communicate verbally. We will establish the presence of cancer-related pain for the last 24 hours using the VAS  at time RNs coming to work on the intervention ward or control ward as temporary staff will be excluded from participating in the study. We will exclude patients admitted onto the ward because of trauma or planned and/or acute surgery.Our intervention will focus two key components: (1) a theory-based education for ward RNs caring for patients with a cancer diagnosis and (2) the introduction and implementation of guidelines for daily, systematic pain assessments for those patients on the wards suffering from cancer-related pain.The educational intervention for nurses will be arranged in the form of workshops. In this study we have defined the concept of workshop as an interactive activity aimed at promoting learning about a pre-set subject or topic. Workshops are said to support the participants in the process of jointly creating insight, knowledge and understanding. It is a democratic and social process  created The content of the workshops will be based on the Scottish Intercollegiate Guidelines Network for the treatment of cancer pain in adults , and on The educational intervention consists of a set of workshops (180 minutes each) and each workshop will include 15 RNs from the intervention ward. The first workshop will comprise sessions on pain anatomy, physiology and pain analysis through case study discussions. The second workshop will comprise subjects such as different treatments for cancer-related pain and case study discussions Figure . The worGuidelines for pain management and systematic pain assessment will be implemented on the intervention ward immediately following the educational intervention. The daily pain assessment will be integrated as a required standard parameter together with the ordinary routine vital parameters such as temperature, pulse and blood pressure. Routine vital parameters on the wards are performed by RNs representing three different work shifts and pain will thus be assessed by the VAS at three points in time i.e. 4 am - 6 am, 1 pm - 3 pm and 7 pm - 9 pm. Pain intensity, nursing action and nursing follow up will be documented in the patient-specific study protocol at the bedside.VAS is an instrument consisting of a 10 cm horizontal line, which measures pain intensity from "no pain to "worst pain imaginable". Patients participating in the study will be asked to assess current pain intensity by marking the line between the two extremes . The avePatients with a cancer diagnosis admitted to the control ward will receive the usual care from their RNs, i.e. care for their patients according to normal practice.Our primary outcome will be RNs' attitude and knowledge as measured using a modified version of the KAS  at baselThe original KAS consists of 40 items where items 1-22 are false-true statements, items 23-36 are multiple-choice questions and items 37-40 consist of two case studies . KAS hasWe will measure pain intensity and pain impact on daily life among the patients using the Brief Pain Inventory - Short Form . The patBPI-SF is a pain assessment instrument developed for cancer patients . It is wComparability between intervention and control groups will be assessed at baseline and at end of study to check for differences between participants, i.e. RNs and patients. Outcomes (KAS and BPI-SF) together with variables such as demographics, diagnosis, age, RN's length of experience and education, both at baseline and at end of study, will be compared between the intervention and control groups using both univariate and multivariate techniques . Data wiWe will conduct the study in compliance with the established ethical guidelines of the Declaration of Helsinki . Under tPatients who meet the inclusion criteria on both participating surgical wards will be invited to take part in the study by the admitting RN or by the RN in charge of the patient. Both written and verbal information about the study and its protocol will be provided. All RNs on both wards will be informed verbally and in writing about the study before participating.This project will train RNs in the field of cancer-related pain and establish routines for pain assessment, which is good. Allowing the nurses to update their knowledge in cancer-related pain management may prove beneficial to other groups of patients experiencing pain. The findings of this study will be used to update present guidelines concerning cancer-related pain management. At present, no known risk can be envisaged concerning the patients' physical and/or mental health.This study is due to be completed end of December 2011.Nursing care is nowadays acknowledged as an increasingly complicated activity and "nursing complexity is such that it can be seen as the quintessential 'complex intervention" . To be aEPIC: European Pain in Cancer; KAS: Knowledge and Attitudes Survey Regarding Pain; RCT: Randomised Controlled Trial; RN: Registered Nurse; TPB: Theory of Planned Behaviour; VAS: Visual Analogue Scale.The authors declare that they have no competing interests.MG, GB and HK conceived and designed the study and obtained funding. GB and MG drafted the manuscript and HK contributed to editing the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/11/233/prepub