There is a belief that the amount of pain perceived is merely directly proportional to the extent of injury. The intensity of postoperative pain is however influenced by multiple factors aside from the extent of trauma. The purpose of the study was to evaluate the relationship between preoperative factors that have been shown to predict postoperative pain and the self-reports of pain intensity in a population of 155 men undergoing radical prostatectomy (RP), and also to investigate if previous pain score could predict the subsequent pain score.The correlation between potential pain predictors and the postoperative pain experiences during three postoperative days was tested (Pitmans' test). By use of a logistic regression analysis the probability that a Visual Analogue Scale (VAS) score at one occasion would exceed 30 mm or 70 mm was studied, depending on previous VAS score, age, depression and pain treatment method.Age was found to be a predictor of VAS > 30 mm, with younger patients at higher risk for pain, and preoperative depression predicted VAS > 70 mm. The probability that VAS would exceed 30 mm and 70 mm was predicted only by previous VAS value. Day two however, patients with epidural analgesia were at higher risk for experiencing pain than patients with intrathecal or systemic opioid analgesia.The results show that it would be meaningful to identify RP patients at high risk for severe postoperative pain; i.e. younger and/or depressive patients who might benefit from a more aggressive therapy instituted in the very early postoperative period. Pain is one of the major concerns in the postoperative care, not only because of the suffering it causes, but also because of its potential association with the process of recovery . There iThere can be several explanations for this and studies have shown that the threshold for pain is different in different patients .In patients with prostate cancer, radical prostatectomy (RP) is the most common technique for removing the prostate gland and it is a procedure performed with increasing frequency . In RP, Different factors have been found to influence the intensity of postoperative pain. In previous studies we have shown that the method for postoperative pain treatment after RP was of importance ,10. A prPreoperative expectations of pain have been found to correlate with the postoperative pain experience ,12. PercPsychological factors such as anxiety and/or depression have been considered as important predictors of postoperative pain ,15. Age Nurses are in a unique position to supervise and assist patients in pain and in the treatment thereof, considering the extensive time nurses spend with the patients when compared with other health-team members . NursingSeveral studies have investigated the relationship between pre-surgical clinical factors and postoperative pain. The influence of previous pain score  on the next-coming pain scores has not earlier been studied in this group of patients i.e. if patients who are in pain directly after surgery continue to be in pain during the postoperative recovery. The purpose of the present study was therefore to evaluate the relationship between preoperative factors that have been shown to predict postoperative pain and the self-reports of pain intensity in a population of 155 men undergoing RP, and also to investigate whether a previous pain score could predict the subsequent pain score.The study was a prospective, explorative study conducted from January 2003 to June 2004. After approval was obtained from the Ethics Committee of the Sahlgrenska University Hospital, Sweden, patients on the waiting-list for RP, were recruited for the study.The demographic form comprised questions about age, civil status, education, employment, time on waiting list previous surgical experiences, previous postoperative pain experiences and postoperative pain expectations.Data of physical status classification according to the American Society of Anaesthesiologists (ASA score), psa, weight, surgery time, intra-operative bleeding, pain treatment method and opioids consumption were collected from the patients' records.Pain was measured with a VAS (0–100 mm) on which the patients' pain intensity was represented by a point between the extremes of "no pain at all" and "worst pain imaginable". The simplicity, reliability and validity of the instrument make the VAS a good tool for describing pain severity or intensity .The analysis of the VAS scores is a frequently discussed matter. In studies using the VAS, a score of more than 30/100 mm is often used as a limit to indicate inadequate analgesia and a VAS score of more than 70/100 mm is a common breakpoint for defining severe pain . A mean The HAD scale  has beenMHLC measures expectancies about control, and was developed for prediction of health related behaviour . The scaThree weeks before surgery, consecutive patients on the waiting-list for RP received a letter with written information about the study. Patients willing to participate signed and returned a consent form. At the same time the patients answered the form about demographics and the MHLC questionnaire. The day before surgery, the patients answered HAD and they were informed about the VAS. Patients were asked, by the author (KWE), about pain at four hours after surgery and "worst pain" experienced during the last 24 hours at intervals of 24, 48 and 72 hours. The patients were asked to put a mark on a 100 mm line, representing "worst pain" experienced.Initially EDA was the routine treatment for postoperative pain in these RP patients. About a year after the beginning of the study, and after evaluating EDA as an ineffective method for pain treatment in this group of patients, the method for postoperative analgesia was shifted to ITA. Study patients who were deemed unsuitable for either EDA or ITA, received systemic opioid analgesia (SOA) for pain relief.After the operation, the patients were supposed to stay in the postoperative anaesthesia care unit (PACU) until the pain relief was sufficient. When the patients returned to the ward, each EDA and ITA patient had a checklist for basic and specific controls e.g. VAS, sedation, motor function and hemodynamics. The patients given only SOA for pain relief did not have any special protocol for pain assessment. The recommended pain level was to be VAS < 30–40 mm on a 100 mm scale. All patients received paracetamol (1 g × 3–4) starting preoperatively and continuing postoperatively until the patients left the hospital. If pain relief was not sufficient on the ward, additional doses of ketobemidone  were given systemically on a PRN (as requested) basis. Oral rescue analgesics (tramadol and NSAID's) were given at the discretion of the surgeon on the ward.SPSS (version 14.0) for data analyses was used to analyze the data. Continuous variables are presented as means and standard deviation, and categorical data are presented as number and percent. By use of a non-parametric test (Pitmans' test)  the corrOf the 181 patients who were invited, 155 patients (86%) gave informed consent to participate. The mean age of the patients was 63 years (range 43–73). Most of the subjects (89%) were married, and about one third had elementary education. Half of the patients were retired. After being diagnosed with prostate cancer, 41% of the patients had to wait more than three months for their operation. Data from the patients' records are presented in Table A pain level higher than VAS 30 mm during the three postoperative days was predicted by age (p = 0.044) and there was a correlation (p = 0.016) between age and "worst pain", with younger patients reporting higher pain scores than older Table . There wOne hundred and five (68%) patients had previously undergone surgical procedures. Of these patients, 36 (44%) had experienced moderate/severe pain. Moderate/severe pain after the RP was expected by 121 (78%) patients and was experienced by 105 (68%) patients. Patients with previous experience of postoperative pain expected higher pain scores (p < 0.01), though this was not actually experienced. Only four patients reported some kind of pain (e.g. back problems) before surgery.The HAD questionnaire was answered by 133 (86%) patients. Possible or probable preoperative anxiety was reported by 33 (25%) of these patients  reported mild, 69 (45%) moderate and 36 (23%) severe pain for one or more days Figure . Mean paMean PACU-time was 14 ± 7 hours. Patients with severe pain had the longest PACU-time . Twenty (13%) patients had a pain score > VAS 30 mm after four hours. During the rest of day one, pain subsequently increased with 85 (55%) patients reporting a pain score > VAS 30 mm. In the twenty patients with VAS > 30 mm after four hours, pain increased in 14 (70%) patients.Of the 155 patients, 90 (58%) received EDA, 50 (32%) ITA, and 15 (10%) received SOA for their postoperative pain relief  between VAS at four hours and the rest of day one were 0.52 (p < 0.001), Pitman's test , betweenBy use of logistic regression analysis the probability that VAS at one occasion would exceed 30 mm or 70 mm was studied, depending on previous VAS values, age, depression and pain treatment methods. The probability that VAS day one would exceed 30 mm (p = 0.017) and 70 mm (p = 0.0103) was predicted only by VAS after four hours Figure . The preThe study has demonstrated that in RP patients, age and depression are found to be predictors of postoperative pain. A pain level > VAS 30 mm at one occasion during the three postoperative days was predicted by age, and a pain level > VAS 70 mm was predicted by depression. From a treatment perspective we wanted to predict whether the patient needs treatment in the next future, so that we, in the best case, can give the treatment before the pain has increased above 30 mm on the VAS scale. For that purpose we did not need to make a prediction at baseline or by use of the baseline values. We needed to make a prediction with a time horizon of a few hours only to get the opportunity to treat the patient. By use of logistic regression analysis we found that the only factor that could predict pain was the previous VAS score, except for day two, when we found that patients with EDA reported significantly higher pain scores than the patients with other pain treatments. A surprisingly finding was that as much as one out of four patients (23%) of the total sample and 30% of the EDA patients experienced severe pain.Patients undergoing the same type of surgery are often given the same type of postoperative pain treatment, but age-related pharmacokinetic and pharmacodynamic factors may influence the variance in analgesic needs . With a Preoperative emotional variables such as anxiety and depression have been found to influence pain experience. In this study we found depression to be of importance for a pain level > VAS 70 mm. In a previous study, we found depression to be a predictor of pain in RP patients, and that preoperative depression also affected pain and depression after discharge from hospital . Even inRegarding MHLC, it has previously been shown that patients who are more internal, i.e. who believe that they can influence and are responsible for their own health , have loIn a multivariate analysis model we found the only predictor of the severity of postoperative pain to be the previous VAS value. Seventy percent of the patients with a pain score > VAS 30 mm at four hours after surgery continued to be in pain. Pre-emtive analgesia is a frequently discussed matter but studies comparing pre-incisional with post-incisional treatment have failed to provide convincing evidence for the value of preemptive analgesia . Kissin Several studies have reported EDA with local anaesthetics combined with opioids as a safe and effective method ,34. SomeNurses play an important role in the pain management. They assess and document pain, decide whether to administer analgesics, and they monitor the effect of medication which is prescribed and administered in a variety of ways. In the present study supplemental systemic opioids were supposed to be given on a PRN basis until pain relief was sufficient. There is evidence that nurses are conservative when making decisions about opioid dosing and frequency of administration . ConsistThe method for postoperative pain relief was gradually shifted from EDA to ITA which may have affected the study result. However, the patients were not assigned to different pain treatment methods depending on patient factors. All of the patients were men, with the same diagnosis, who underwent the same kind of surgery and all patients were interviewed about their pain experiences in a consistent way and the result should therefore be valid.Patients were asked once a day about their "worst pain" experienced during the preceding 24 hours, though it was not possible to meet all patients for an interview more often than once a day. This method of pain assessment with an overall daily retrospective estimation may overlook periods with more or less pain . Howeverper se. It could however also imply that pain once manifested is not easily converted despite a generous analgesic treatment. This may be more evident in subgroups of patients, e.g. younger and depressive patients, who might benefit from a more aggressive therapy instituted in the very early postoperative period. When using EDA, the patients and the epidural catheters should be observed closely and systematically, by adequately trained members of the staff competent to detect inadequate analgesia and potential problems with the use of EDA, and to implement proper solutions [The results of the present study show that it would be meaningful to identify at least a subgroup of RP patients at high risk for severe postoperative pain. This could be related to an insufficient treatment olutions . This reThe authors declare that they have no competing interests.KWE and BS were responsible for the study design. KWE performed the data collection. All authors contributed to the data interpretation, helped to write the manuscript and approved the final version.The pre-publication history for this paper can be accessed here:


Pain and emesis are the two major complaints after day case surgery. Local anaesthesia has become an important part of optimizing intra and post-operative pain treatment, but is sometimes not entirely sufficient. The aim of the present study was to study the effect of adding an ankle block to a multi-modal analgesic approach on the first 24-hour-need for rescue analgesia in patients undergoing elective Hallux Valgus surgery.Prospective, randomized patient-blind study comparing ankle block with levo-bupivacaine, lidocaine and Saline placebo control.Ninety patients were studied comparing ankle block (15 cc) using levo-bupivacaine 2.5 mg/ml, lidocaine 10 mg/ml or placebo  on day-case elective Hallux Valgus surgery, supported by general anaesthesia in all cases. Primary study endpoint was number of patient's requiring oral analgesics during the first 24 post-operative hours.st 24 postoperative hours, there was no difference seen between placebo and any of the two active local anaesthesia studied. The only differences seen was that both lidocaine and levo-bupivacaine reduced the intra-operative need for anaesthetic (sevoflurane) and that levo-bupivacaine patients had a lower need as compared to the lidocaine patients for oral analgesics during the afternoon of surgery.Ankle block had no effect on need for rescue analgesia and pain ratings during the 1Adding a single shot ankle block to a multi-modal pain management strategy reduces the need for intra-operative anaesthesia but has no major impact of need of rescue analgesics or pain during the first 24-hour after surgery. Multi modal pain management has become standard of care especially in day case surgery . Local aThe aim of the present study was to evaluate the effects of adding a single shot ankle block to a routine multi-modal pain strategy for the management of Hallux Valgus surgery performed under general anaesthesia.After informed consent 90 healthy America Society of Anesthesiology functional classes 1–2 patients undergoing elective Hallux Valgus surgery ad modum Turan were studied . The stuGroup A had 15 cc levo-bupivacaine 2.5 mg/mlGroup B had 15 cc lidocaine 10 mg/mlGroup C Placebo Control had 15 cc of salineThe performance of the ankle block was; "the posterior tibial nerve" by 5 cc posterior to the medial malleoli, "the peroneal nerve, superficial and deep" by 6 cc on dorsum of the foot and "the sural nerve" by 4 cc posterior to the lateral malleoli.All patients followed the routine pre and postoperative protocol of our institution. They were asked to refrain from eating for 6 hours and drinking for 2 hour prior to surgery.After establishment of an intravenous line all patients were given 8 mg betamethasone, 0.3 mg alfentanil and 30 – 50 mg propofol. After sedation the patients received the ankle block in accordance with the randomisation in a single blinded fashion.All patients also had 10 cc of 10 mg/ml lidocaine subcutaneous around the surgical incision given by the orthopaedic surgeon (IT) under sterile conditions right prior to incision. A general anaesthesia was administered by means of sevoflurane in oxygen/air by mask. Sevoflurane was titrated according to clinical needs by the attending anaesthetist (JJ). Sevoflurane concentrations were continuously monitored by side-stream gas analysis. Peak end-tidal and mean end-tidal sevoflurane concentrations were recorded and used for evaluation of need for anaesthesia.Immediately after surgery anaesthesia was discontinued and the patients moved to the recovery area, if fully awake and alert possibly bypassing conventional recovery room stay. After arrival in recovery area all patients had an initial oral dose of etoricoxib 120 mg and a loading dose of 30 mg/kg paracetamol.Patients were discharged when awake, and ambulant with minimal and acceptable levels of subjective pain (VAS < 4).At discharge all patients were provided with take-home analgesic medication; Etoricoxib 120 mg, paracetamol 1 gr. and dextropropoxyphene 100 mg. All patients were provided with oral and written instruction about pain management at home they were informed to take:• Regularly etoricoxib 120 mg once daily• Additional paracetamol 1 gr. oral when needed (up to four grams daily), as initial pain therapy• Additional dextropropoxyphene 100 mg oral if paracetamol had reviled pain within 30 minutesThey were instructed to take patacetamol and dextropropoxyphene not by routine, but only when needed.st 24 post operative hours, need for any pain medication; paracetamol and dextropropoxyphene, as well as pain ratings at a verbal pain scale; no pain, little pain, pain, severe pain [Patients were instructed to fill in a protocol for the first postoperative day; 1ere pain .Patients' demographics are presented as mean and standard deviation. All results are given as median and range. None-parametric Chi-square test or Mann-Whitney U-test when appropriate studied differences between groups. The number of patients (30 in each group) was determined by a pre-study power analysis based on the findings in a pilot study in our institution; need for additional analgesics in the control (placebo) group of 70% and a clinical relevant absolute reduction in patient taking additional analgesics of 30%, corresponding to clinical significant effect of an ankle block being that only 40% of patients needing additional analgesics during the first postoperative 24 hours with a power of 90 % at p < 0.05. All statistics were made in StatView™ on a Macintosh computer system.There was no significant difference in patient demographics Table The number of patients that needed further oral analgesics during the first 24 postoperative hours was 21, 9 and 17 out of 30 for the lidocaine, levo-bupivacaine and placebo group of patients respectively with no significant difference between either of the two active treatments as compared to placebo, Table painful during afternoon and 10 (11 %) in the evening on the day of surgery. In the morning and afternoon on the 1st postoperative day 6 (7%) and 18 (20%) patients respectively scored the intensity as painful. Five patients made a rating of severe pain on 1 occasion and 1 patient on 2 occasions, afternoon and evening day of surgery. No difference in pain ratings was seen between the groups figure Pain ratings were overall low, and waste majority of patients made pain ratings as no or little pain. Nine patients 10%) made a rating of 0% made aNo complications or adverse events were noticed during the follow-up period.The interpretation of our results should be done with caution, as the study design is complex. Our study is negative; we could not see any statistical significant difference between the levo-bupivacaine or lidocaine block and placebo with regard to our primary study endpoint; number of patients that needed oral pain medication during the first 24 post operative hours. Interestingly though is that a post hoc separate comparison between lidocaine and levo-bupivacaine revealed significantly less patients taking any further pain medication after a levo-bupivacaine block as compared to the lidocaine block. Also when the patients that received the long-acting local anaesthetic levo-bupivacaine was compared to the combined group of patients either given the short acting lidocaine block or placebo control a significant difference was observed in favour for the levo-bupivacaine block. No difference was however found in the need for "further dextropropoxyphene rescue medication". Also pain ratings were similar between the all three groups studied; the addition of 15 cc of lidocaine 10 g/ml or levo-bupivacaine 2.5 mg/ml did not affect pain ratings during the first 24 postoperative hours as compared to placebo. We found also that adding both 15 cc of levo-bupivacaine 2.5 mg/ml or lidocaine 10 mg/ml as an ankle block prior to surgery to a multimodal pain management during Hallux Valgus surgery decreased the need for intra-operative anaesthesia by decreasing the concentration of sevoflurane needed; however no difference in emergence/recovery time characteristics was noticed.The use of local anaesthetic is not a new concept but a basic component used in clinical practice all over the world. It is important to take into account that all our patient had local anaesthesia, lidocaine, applied locally by the surgeon before skin incision. In order to achieve a rapid onset lidocaine has been the tradition of use in our institution for locally applied anaesthesia. It would of course be of interest to study the effects on postoperative pain by changing to or adding a long acting local anaesthetic to the locally applied block. Already in 1985 Porter and Davis showed that injecting a long acting local anaesthetic into the pseudoartrosis immediately after skin closure gave better postoperative pain relief as compared to placebo after Keller's procedure . The hypIt should indeed be acknowledged that our patients all received a multi-modal analgesic regime. All patients received both bethametasone and a small dose of alfentanil right before induction of anaesthesia. Romunstad et al has convincingly shown the analgesic effects of steroids , improviOne may argue that the patients were given an extensive peri-operative analgesics regime and that in orthopaedic day surgical procedures such as knee arthroscopy the need for postoperative pain medication is not that extensive . It is rWhen added to a multi-modal pain management a single-shot ankle block was not enough to show any significant difference in the need for further analgesic and did not change the pain ratings during the first 24 hours after elective Hallux Valgus surgery as compared to placebo. Adding an ankle block reduced however the intra-operative anaesthetic requirement and a levo-bupivacaine block provides similar beneficial intra-operative effects but reduced also the need for rescue analgesics during the first 24 hours as compared to the lidocaine block.There are no competing interests; this is a basic academic research initiative.JJ has had the main responsibility for the study and manuscript preparation.


Purpose. To evaluate the results of patient symptoms and radiologic outcomes of cystoretroperitoneal shunt (CRS) technique in the treatment of symptomatic simple renal cysts. Patients and Methods. In a prospective study, 37 patients with a simple renal cyst were treated with ultrasound-guided percutaneous CRS-catheter. Radiological success was indicated as no recurrence of the cyst or a reduction in cyst volume by at least half. Results. CRS technique was performed successfully in 36 patients with a simple renal cyst. The mean size of all cysts decreased from 8.8 cm (range 7 to 14) to 1.7 cm . Symptomatic success (pain relief) was achieved in 29/36 (80.5%) of patients, and radiographic success was achieved in 23/36 (63.8%) of patients, with a median follow-up of 16 months (range 6 to 24). Conclusion. Ultrasound-guided percutaneous CRS technique for simple renal cysts is fast, safe, effective, and inexpensive. Simple renal cysts are common, with incidence increasing with age from 0.22–0.55% in children to >5% in the fourth decade, and up to 36% in the eighth decade of life . The BosAlthough simple renal cysts are usually asymptomatic, flank pain is the most common symptom. A palpable flank mass, hematuria, hypertension, and compression of the pelvicaliceal system also can occur . Pain, iOpen surgical cyst decortication for pain relief through an abdominal incision is associated with considerable morbidity and protracted convalescence . PercutaOpen surgical or laparoscopic decortication of cysts creates a window between the renal cyst and retroperitoneal area. We designed a new technique in order to achieve the same goal and eliminate the risks associated with both surgeries. In this study, we describe and analyze the feasibility, safety, and efficancy of “cystoretroperitoneal shunt (CRS) technique” in simple renal cysts.From April 2004 through February 2008, 37 patients underwent the CRS technique for symptomatic simple renal cysts. The study was approved by the local ethics committee. All patients signed a detailed consent form that listed details about the procedure and possible complications. All cysts were unilateral, single and in Bosniak category I [All patients were evaluated in the urology clinic, where the cysts were localized and characterized by ultrasonography. Additionally, computed tomography was performed for Bosniak classification. The volume of the cysts was calculated with an ellipsoid formula, whereby the product of the three orthogonal diameters was multiplied by 0.52 (volume = height × width × length × 0.52). The volume of the cyst was compared to that estimated before treatment and represented as a percentage of the initial value. Radiological success was designated as no recurrence of the cyst or a reduction in pretreatment cyst volume by at least half. The following studies were also performed at enrollment: after 7 days, and after 1, 3, 6, 9, 12, 18, and 24 months, clinical examination and laboratory tests that included urinalysis, serum creatinine level, and coagulation profile.Flank pain and mass, hypertension, and hematuria were documented before treatment. The subjects were considered to have hypertension based on data obtained from their histories and if the values of their systolic/diastolic blood pressure were 140/90 mm Hg or greater. The blood pressure measurement was conducted on the day before the procedure and at each examination during the follow-up period. The patients were also asked if they did or did not have pain. The severity of pain was not evaluated.The CRS technique was performed with a single step 7 French ×50 cm drainage ring catheter  . The catt, Mann Whitney and Fisher's exact tests were done. A value of P < .05 was considered significant.Statistical analyses were performed with GraphPad Prism 4 software for Windows. Student's P < .001). The mean volume of the cysts was 354.8 ± 38.3 mL . The cysts volume dropped less than 50 mL in volume in all patients (100%) in 24 hours after the CRS-catheter insertion. During follow-up period, one (2.7%) of the cysts recurred shortly after disappearance. We excluded that case from our study group when the catheter was found out of the cyst. The disappearance of the cyst was sustained in other patients 36/37 (97.3%) until the CRS-catheters were removed . The mean volume of the recurrent cysts was 180.5 ± 73.5 mL . Only patients with giant cysts underwent further treatment with percutaneous aspiration with ethanol injection. Only seven patients (19.5%) with a giant cyst and persistent pain underwent further treatment with percutaneous aspiration with ethanol injection. Aspiration with ethanol injection alleviated pain in all the patients. Four patients had no pain and three reported decrease in its severity. The subjects were 15 men and 22 women with a median age of 48.5 years (36–65 years) . The medFor the 13 patients with associated hypertension, six (46.1%) had well-controlled blood pressure with no medication after the decrease in cyst size. One patient had a wound site infection three days after insertion of the catheter, which was resolved by oral antibiotherapy . Microbiologic and cytologic investigations revealed normal findings.This study reports on a new CRS-technique used with 37 patients and a median follow-up of 16 months. Radiological success was achieved after catheter removal in 63.8% of patients. Flank pain was present to variable degrees in all patients before treatment. Ultrasonography and computed tomography were used both for diagnosis of renal cyst and to rule out nonrenal etiology for pain. Following treatment, the flank pain subsided in all patients whether resolution of the cyst was complete or partial. Symptomatic success (pain relief) was accomplished in 80.5% of patients after removing the CRS-catheter. Laparoscopic decortication is effective and some authors recommended it as the next step for a recurrence after simple aspiration that initially relieved the pain [Hypertension associated with simple renal cysts is likely to disappear after treatment. In our study, six hypertensive patients 46.1%) benefited from treatment with normalization of blood pressure. Similarly, Touloupidis et al. found that, of 61 patients with hypertension, 29 had improved blood pressures after sclerotherapy of simple renal cysts [.1% benefRenal cysts are common in the adult population . With a Laparoscopic decortication of symptomatic renal cysts has been used since the early 1990s , 16. AltPrevious studies suggested that cyst recurrence after sclerotherapy was a result of inadequate sclerosis of the cyst wall epithelial cells, which continued to produce fluid into the cyst . The sec As in other studies, there was an obvious difference between radiologic and symptomatic success in our study , 15. AllThe major limitation of our study was the lack of a control group for comparison of our results. We might have randomly assigned patients into two groups , 5 in a In conclusion, the CRS-technique is minimally invasive, well-tolerated, and easily administered under ultrasound guidance and does not require hospital admission. It can be offered to patients who may prefer to avoid risks associated with sclerosing agents and general anesthesia. As for every novel technique, further larger and controlled studies are needed to evaluate the value of the CRS-technique in the treatment of symptomatic simple renal cysts.


The comorbidity of chronic pain and depression has been consistently associated with a poor prognosis and greater disability in patients as compared to those suffering from each illness alone. This further has implications on significant financial costs to the patients and to our society. The biological underpinnings of major depression and chronic pain have considerable overlap in the areas of genetic, structural, functional, neuroendocrine and neurotransmitter functionality. Although the field has evolved in the past decade, more efforts should now focus on understanding the biological underpinnings of this shared comorbidity, while shedding light on treatment implications for these two devastating conditions. There is a burgeoning interest in the mind-body connection in mental illness over the recent years. This is further substantiated by a growing body of evidence on the neurobiology of pain and depression given the cross talk between pain and affective pathways, outlining the interactions between affective, executive, cognitive processes and pain experiences. Depressed patients have a four times greater risk, than non-depressed patients, of a chronic painful physical condition (CPPC) while 69% of patients in primary care clinics present with somatic symptoms leaving depression unrecognized and undertreated.2th Edition, Text Revision (DSM-IV-TR), enumerates the presence of symptoms that occur across the physical, psychological and cognitive domains.[et al. the most common symptoms in patients with a mood disorder were back pain, musculoskeletal complaints like muscle, joint or limb aches and pains, sleep disturbances (insomnia), chest pain, dizziness and fatigue.[Current diagnostic criteria for major depressive disorder (MDD), established in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4 domains. DepressiChronic painful physical conditions (CPPC) are common in subjects with MDD and a recent international study has shown that the presence of a CPPC increased the frequency and severity of seven depressive symptoms including depressed mood, lack of interest, psychomotor agitation/retardation, weight gain, insomnia, fatigue, and impaired concentration. Some phyThere is a bidirectional complex relationship between pain and depression with chronic pain as a predictor of subsequent major depression, and vice versa. Co morbi7This article is an attempt to review current scientific understanding of overlapping pathophysiological processes and circuitry of pain and depression that would help shed some light on the neurobiology and treatment implications that could potentially have significant relevance on clinical outcomes for our patients.The co morbidity of chronic pain and depression has been consistently associated with a poorer prognosis and greater disability in patients as compared to those suffering from each illness alone.10 The fi910The biological mechanisms underlying the link between pain and depression are heterogeneous.–17 AreasThe complexity of genetic determinants for chronic pain and depression involves the multiple polymorphic nature and varying contribution of the genes which may contribute to these disorders. Although many genes have been implicated in major depression, the genes regulating serotonergic function such as the serotonin-transporter-linked promoter region 5HTTPR or the serotonin 2A (5-HT2A) are consistently identified.18 Other 21At the cellular level, inflammatory signals from distress or pain are conveyed primarily from the periphery to microglia.24 In majNeuroimaging studies have allowed for examination of the areas of the brain which are structurally or functionally aberrant in both pain and depressive syndromes. The dorsolateral prefrontal cortex (DLPFC) is the area of the brain which regulates influence over limbic structures and is a crucial part of the executive function network. Studies 30Neuroendocrine abnormalities such as dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis have been recognized in both depression and chronic pain disorders, such as the inability to suppress cortisol as seen in patients with fibromyalgia. Physical34The role of neurotransmitters, peptides and endogenous opioids continues to be a focus of research in chronic pain syndromes and depression. Serotonin, a neurotransmitter well known for its usefulness in antidepressants, has been shown to have antinociceptive and pronociceptive effects depending on the receptor subtype and region of the central nervous system.15 Descen111141The biological underpinnings of major depression and chronic pain have considerable overlap in the areas of genetic, structural, functional, neuroendocrine and neurotransmitter functionality. The pathology that is similar between these illnesses therefore results in similar phenomenology that is seen in clinical practice.There is sufficient evidence to suggest that nearly 30-60% of patients with depression also suffer from pain syndromes. More oftStress seems to play a role as a precipitant and a perpetuator in both pain and depression. In addition, both of these syndromes seem to share neurobiological underpinnings including the rubric of genes, brain circuitry, dysregulation of neurochemistry , inflammatory processes, neuroendocrine and neurotrophic signaling. Neuroanatomic regions that play a role in both these syndromes include the limbic and paralimbic prefrontal cortical areas – amygdala, hippocampus, insula, anterior cingulate cortex (ACC), ventromedial prefrontal cortex (vmPFC) as well as more "cognitive" and integrative brain areas.There is a bidirectional relationship between pain and depression with the symptoms of one worsening the other. These co morbid conditions also complicate treatment response and increase risk for relapse, thereby warranting the need to address both of these problems concurrently.4344 Cons431


Home based care (HBC) has been an important component of the response to the AIDS epidemic in Africa, and particularly so before antiretroviral therapy (ART) became available. Has HBC become unnecessary now that ART is available in many African countries? One way to investigate this is to assess the changing need for comprehensive HBC as an ART programme becomes available. The Bangwe HBC programme in Malawi has been collecting data since 2003 before ART became available in 2005/6. Has the introduction of ART changed the clinical needs for HBC?Information obtained at initial assessment and follow up visits of patients receiving HBC were combined to assess case severity, survival and the response to treatment. This information was used to assess trends in mortality and the incidence, duration and severity of common symptoms over a six year period in a defined urban population in Malawi.1266 patients, of whom 1190 were followed up and of whom 652 (55%) died, were studied. 282 (25%) patients died within two months of being first seen with an improvement between 2003-2005 and 2006-2008 of reduced mortality from 28% to 20%. 341 (27%) patients were unable to care for themselves on first assessment and 675 (53%) had stage 4 AIDS disease. Most patients had a mix of symptoms at presentation. Self care increased somewhat over the six years although case severity as measured by WHO staging and nutritional status did not.350 patients were on ART either started before or after initial assessment. There were significant barriers to accessing ART with 156 (51%) of 304 stage 3 or 4 patients first assessed in 2007 or 2008 not receiving ART.Over the six year period new HBC cases reduced by 8% and follow up visits increased by 9% a year. Between 4 and 5 people sought HBC for the first time each week from an urban health centre catchment of 100,000, which required 37.3 follow up visits each week.Since the availability of ART in the local health facilities and despite strenuous efforts to persuade people to seek HIV testing and ART, in practice barriers existed and half the eligible HBC patients did not have access to ART. This is one reason why the clinical need for HBC services had not changed much. In terms of quantity of care the number of new patients seeking HBC reduced by 8% a year. In terms of content of care, while there had been a marginal increase in self care the severity of illness had not changed and the survival of a significant proportion of patients generated the need for repeat visits, which increased by 9% a year. In conclusion, although the content has changed the need for HBC has not diminished despite the availability of ART. Home based care (HBC) of people living with AIDS is an established component of the continuum of care and support advocated by WHO and UNAIDS  and planThe Bangwe project is a home based care (HBC) project run by the Department of Community Health, College of Medicine, University of Malawi. While providing a standard HBC service to the people of Bangwe, a township of 88,000 people adjacent to the town of Limbe near Blantyre, the opportunity is taken to collect data on the health problems of patients, their response to treatment and their nutritional status. Antiretroviral drugs were not being used during the initial study period, but began to become available free of charge in Malawi in 2005.The project has been collecting patient data since January 2003. It has been assessing the value of the national standard treatments for home based care as promulgated by the National AIDS Commission (NAC), and initially assessed the effect of supplementary feeding for the World Food Programme ,13. An AThe study population has been well demarcated and allows estimates of disease frequencies, severity levels of symptoms, rates of recurrences and the duration of episodes. These can be used to extrapolate for planning purposes to larger urban populations . CarefulThe main object of the research was, therefore, to describe the changing pattern of home based care needs as the HIV epidemic matured and as ART became available in a community.The home based care project forms part of a College of Medicine HIV/AIDS Community project which encompasses community action concerning prevention, orphan care and HBC. The project covers 15 villages. Community volunteers are recruited and trained in basic HBC as devised by the National AIDS Commission (NAC). There are usually two HBC volunteers for each village. They identify people who may need HBC, and if requested, refer the patient to the HBC team. They accompany the member of the team to see the patient, offer to undertake support tasks if the patient has no carer, and do follow up visits to assess progress and future needs.The team, three nurses and three HBC assistants, supported by the Department of Community Health of the College of Medicine, provides the clinical care in line with national guidelines. The nurse visits the patient and confirms that the patient has a condition requiring clinical care and is unable to get to a health facility. An initial assessment at the first visit by the nurse identifies the presenting symptoms and signs. Nurses are trained in and use WHO clinical staging. Patients are followed up usually weekly or fortnightly after initial assessment depending on the needs of patients. Follow up visits are stopped once the patient no longer needs clinical care or is able to get to the health centre. Each nurse and HBC assistant carries a standard kit containing dressings and drugs and these are dispensed to treat most of the common opportunistic infections and symptoms such as chronic diarrhoea free of charge. Micronutrients and food supplements, which are sometimes distributed by NAC, are dispensed when available to those who are malnourished.Positive living advice is offered to each patient in their home and patients are encouraged to attend a patient support group which has about 80 members at any one time and at which positive living issues are discussed. Positive living advice in Malawi includes advice about the prevention of AIDS progression in HIV positive patients and HIV infection in their partners. The features of the comprehensive HBC include therefore opportunistic infection treatment, symptomatic treatment of chronic diarrhoea, neuropathic pain and other AIDS related symptoms, skin care, micronutrient supplementation, advice about positive living, social support through volunteers and the patient support group, prophylactic antibiotics such as Cotrimoxazole, advice about the importance of HIV testing, the value of ART and the need for ART retention and adherence, the identification and management of side effects of ART and referral for ART, TB treatment and other hospital services.The first occasion a registered patient started ART was 15 March 2004. Initially ART was only available free from the two neighbouring districts where Medicin Sans Frontiere (MSF) was located. Only a few patients managed to travel and obtain their drugs there. The first patient to get their drugs from a Ministry of Health facility was in April 2005 at Queen Elizabeth Central Hospital, Blantyre. An ART clinic was opened in Bangwe in March 2006. By January 2007 waiting times for ART were usually less than two months.The study area is comprised of the nine villages in Bangwe, Mzedi and parts of Limbe East wards with a population of 56,700 estimated in the last census taken in 1998. The study area was increased in 2004 to include Naminyango ward, which together with the projected population growth gives an estimated population in 2007 of 88,000. The area is an urban township in the City of Blantyre, which has a population density of 3000 per square Km. Each township is split into villages of about 4,500 people. Half the population in Bangwe is living below the poverty line, which in 2006 was equivalent to $0.50 per person per day . AntenatAn initial assessment form was completed at first visit. The form included basic demographic data and clinical information. A follow up form was completed at each follow up visit. No patients were discharged. Once a year in August patients who had not been seen within three months were visited to check how they were and their date of death, date of starting ART or a date of a move out of the area was recorded as appropriate.st August 2008. Patients seen in the 5 1/2 years who were aged between 15 and 70 years with a presumptive diagnosis of AIDS in stages 2, 3 or 4 were included in the sample. Those patients with an initially reported negative HIV test and for whom a positive test result was not available later were excluded from the trend and survival but were included in the workload analyses and description of presenting clinical features  were married, a third (35%) were either divorced or widowed and 10% single, which for the latter two groups may compromise household caring capacity. The majority of patients in Bangwe were Christian with 11% Muslim. The average number of people in the households was 5.1.Many patients presented in advanced stage of disease, with 675 (53%) having stage 4 disease. A slightly larger proportion of patients presented with Stage 2 disease in 2007 and 2008 than in previous years. However there was no change in the proportions of patients with advanced disease over the period  (Table HIV counselling and testing (HCT) was becoming more available and popular in Malawi. Of the home based patients seen at first assessment just over half had already been tested, changing from 22% in 2003 to 74% in 2008. The vast majority (84%) who had not had a test said they wanted to have one, increasing from 70% in 2003 to 100% in 2005 but down to 78% in 2008. HCT became available at the local health centre in 2005 and in the patient's home to those unable to get to a testing site in 2008.TB had been treated in 34% of patients prior to being seen by the home based care team. The median time between TB diagnosis and being seen by the home based care team was 20 weeks (25% in 7 weeks and 75% in 96 weeks). Most of these patients (385 of 423) were on TB treatment at the time of assessment. 329 where treated for pulmonary and 56 for extra-pulmonary TB. There were fewer patients on TB treatment in the later half of the study period, with 31% in 2003 and 26% in 2008  (Table 2 on enrolment. A fifth (20%) was severely malnourished below 16 kg/m2. There was no change in nutritional status of patients when first seen over the six years .Nearly all patients (93%) thought they had lost weight. Of those who could remember their healthy weight, the average weight loss was 14 kg. The mean BMI at presentation was 18.3 kg/m925 (73%) of the patients at initial assessment were able to care for themselves and 367 (30%) said they were able to continue normal activities. Of the others, many had multiple needs for caring support. A fifth needed help with washing, walking or the toilet, 12% with dressing, and 6% with eating  reduced from 10.1% in 2003 to 4.7% in 2008.93 (7%) of patients presented with lymphadenopathy. Of these patients just over half (51) were categorised as persistent generalised [more than three node groups with two nodes of more than 1.5 cm diameter for more than one month with no obvious cause].A number of patients presented with Kaposi's sarcoma. Data were collected specifically to identify these patients from 2005 onwards. Of this recent series of patients, 8.4% had Kaposi's sarcoma, most commonly of the leg and groin. 13 of the entire study population developed Kaposi's sarcoma after initial assessment.Specific diagnosis required to stage AIDS using the revised WHO classification were collected from December 2005. The number of specific diagnoses identified will have been an underestimate because of the failure of hospitals to document diagnoses in the patient's health passport. The most common diagnosis was recurrent upper respiratory infection followed by severe bacterial infection and a past history of oral candidiasis (Table 158 (12%) patients were on ART treatment at the time of initial assessment. In addition a further 192 (15%) patients received ART after initial assessment  died. 282 patients (25%) died within 2 months of being first seen and 403 (36%) died within the first four months. There was an improvement in 2 month mortality between the early period (2003-2005) and the late period (2006-2008) reducing from 28% to 20%. Longer term survival of more than six months did not change much between 2003 and 2005 but improved in 2006 and 2007  per year from 4.2 to 2.5 new visits per 1000 population  was not followed up, either because the patient died, was admitted to hospital or moved away. The average number of follow up visits per person was 6.8. The average intensity of visits was 3.9 per year, with a few severely ill patients receiving intensive daily visits usually immediately prior to death.For workload planning purposes, for a total population  of 1000 persons, taking the average workload for 2007 and the first eight months of 2008 there were 2.4 new patients and 19.4 follow up visits a year, equivalent to 4.6 new patients and 37.3 follow up visits a week.The main finding of the study is that despite the advent of ART, the number and clinical needs of HBC patients had not changed as much as might have been expected. There were perhaps two reasons for this. Firstly, although ART became available in Bangwe it was not easily accessible to many sick people. Half the HBC patients with WHO stage 3 or 4 were not on ART. The two common barriers to access when ART did become available were that they were either too sick or refused to be HIV tested. Secondly, of those patients on ART prior to HBC, many were very sick on presentation and received palliative care; a quarter did not survive.For those less sick the role of the home based care has changed to include efforts to persuade eligible patients to have HCT, diagnose and treat TB, and seek ART. Home based care staff and our volunteers are in a good position to do this as they are usually known to the patient, the family and community and have built up trust over time. Because some patients were still resistant to HCT, some of our staff have been trained in HCT and now provide it in the home if appropriate. The other addition to home based care with the advent of ART was home treatment of ART, particularly dealing with side effects, treatment failure and efforts to improve compliance. Our staff were trained in this and have a good referral system both ways with the local health centre and hospital ART clinics. Following national policy they are not able to prescribe ART. For patients who are house bound compliance could be improved if our staff were able to prescribe on going treatment in patients established on ART.There may be a certain amount of substitution of clinical care which should but is not provided at ART clinics. If these clinics fail to provide treatments for HIV related problems such as chronic diarrhoea, skin infections and other opportunistic infections but restrict their services to prescribing and dispensing ART then known HBC patients, although ambulant, will tend to seek care from the HBC team who are known by the patients to have appropriate drugs and skills. Efforts need to be made, as we have, to reduce this inappropriate substitution by helping to improve the quality and range of ART clinic care.There was a change over the six years in some but not all of the characteristics of the HBC patients when first seen. They became slightly older, less bed-bound and in need of less home care. Chronic symptoms of fever, cough and diarrhoea were less common, as was the proportion on TB treatment. Many more had had an HIV test and many more were on ART. But WHO staging found at initial assessment was no different over the 6 years. Features which had not changed were nutritional status, the higher proportion of females and being housebound.Survival did not improve until 2006 and the effect of ART was most pronounced in those who had been seen by the team before treatment started, perhaps due to stabilisation by home based care treatment. Survival of a quarter of Stage 3 and 4 patients, some for over five years, who had never received ART, is surprising. The reason could be due to misdiagnosis in patients without known positive HIV serology. However, the analysis specifically excluded those patients who had reported a HIV negative result at initial diagnosis and for whom we had no evidence of seroconversion later. The survival patterns of patients with a known HIV positive result and of patients with no known test result were similar. Misdiagnosis is therefore unlikely. Most patients in the early years of the study were unwilling to have an HIV test and these early cases were almost certainly HIV positive. An alternative possibility for the long survival of these patients therefore is that treatment of opportunistic infections and the other features of comprehensive home based care by the team allowed the immune system to recover and the patients to revert to Stage 2 disease, a stage in which they remained, in some instances, for some years. This issue warrants further investigation.The work load figures give an indication for health service planners of the scale and need for home based care services. While the new patient referral rate was down by 8% a year, follow up visits were up by 9%. For an urban population of 100,000 with an antenatal HIV sero-prevalence of 27% home based care is sought for the first time by between 4 and 5 people each week who together with previously assessed patients generate 37 follow up visits each week. The reason for the increase in follow up visits is thought to be twofold - more patients surviving and more suffering the results of failed treatment or side effects severe enough to require home care. Indeed the number of patients with opportunistic infections has not diminished.In conclusion, the clinical need for HBC services has not changed as much as anticipated despite the advent of ART. In terms of quantity of care, in a community where access to ART is still limited to half the eligible individuals, the number of new patients seeking HBC has reduced by less than 10% a year. In terms of quality of care, while there has been a marginal increase in self care the severity of illness has not changed and the survival of a significant proportion of patients generates the need for repeat visits for the care of these patients. The expertise of HBC staff has expanded. Those patients eligible but not availing themselves of ART need to be exhorted to do so and home management is important for those on ART who are housebound. Overall the need for HBC has not diminished despite the availability of ART in an urban setting where HIV prevalence is high.The authors declare that they have no competing interests.CB conceived the survey and analysed and wrote the first draft. NG and MCB undertook and supervised the data collection. All contributed to and approved the final report.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/370/prepubThe number, frequency duration, severity of presenting symptoms of patients at initial assessment and follow up by the home based care service - Bangwe, Malawi - 2003-2008. A table describes the number and frequency of presenting symptoms of the 1326 patients in the study. It shows the duration of the common presenting symptoms prior to initial presentation such as cough, fever, chest pain and diarrhoea and how long symptoms persisted after treatment dispensed at initial assessment. The table also describes the number and frequency of new episodes of symptoms found at follow up visits.Click here for file


Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level – BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy.Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional  processing of pain. Both structural and functional  scans were obtained and averaged from two different imaging sessions separated by 2–6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions.Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions. Neuroplastic functional and structural changes in chronic pain have been shown in a number of human studies. One of the first reported functional changes related to alterations in activity in the somatosensory cortex in patients with amputation pain In a previous study from our group We tested the hypothesis that regions involved in ongoing somatosensory input  would show cortical thickening  for enrollment. All patients and healthy control subjects provided a written informed consent to participate in this study, which was in accordance to the guidelines of the Human Subjects Committee of the McLean Hospital and in accord with the Helsinki agreement of human experimentation.Patients were recruited through advertisements posted in the local newspapers and in pain clinData were acquired twice from the same patients reported in our previous study All enrolled patients were diagnosed as neuropathic trigeminal pain . The spontaneous and evoked pain location affected the right maxillary branch of the trigeminal nerve (V2) in all patients, which extended to the neighboring branches, ophthalmic (V1) and/or mandibular (V3), in some of them. The protocol consisted of two separated MRI sessions in a period of 2–3 months. Prior to the MRI sessions patients were required to discontinue their pain medication for one dosing interval. All subjects were scanned using a Siemens 3-T scanner. Details for functional imaging are described previously . Using a Velcro-topped (soft side) stick, the brush stimuli were administered at 1–2 Hz (one to two strokes per second) within the marked regions of V2. These mechanical stimuli were given three times during the fMRI session, each for a period of 25s with an interval of 30s of no stimulus. In addition, one T1-weight magnetization-prepared rapid gradient echo (MPRAGE) anatomical scan with 1×1×1.6 dimension was acquired in each MRI session, and both later averaged for this current study . For the HC group, the two MPRAGE were acquired in the same session.http://surfer.nmr.mgh.harvard.edu/) tools After averaging the two T1-weight MPRAGE images to generate a single structural image, hemisphere surfaces were reconstructed and inflated based on the method defined by Dale and Fischl using Freesurfer . Once average functional statistical Ζ-maps (thresholded at a corresponding p<0.05) were created by a generalized mixture model approach The initial functional analysis of cortical areas activated during mechanical stimulation was done by Becerra and colleagues The Occipital Middle Sulcus is surrounded anteriorly by the occipital middle gyrus and posteriorly by the occipital pole, and clearly identified in the individual and average inflated brains.The Somatosensory Cortex in this study was defined as the combination of the primary somatosensory cortex (SI), which includes the central sulcus in its lower bordering posterior wall (putative BA 3b) with postcentral gyrus (putative BA 1), as well as the secondary somatosensory cortex (SII) localized in the subcentral section lateroventral to the postcentral gyrus on the operculum Rolandi (putative BA 43) The ten central sulcus sections labeled in the average hemisphere were automatically converted to each subject's hemisphere using an intermediate registration space, and checked individually for proper conversion. The segmentation and registration method was used to define the 10 sections in SI, and the precentral gyrus, which is the primary motor cortex. The motor cortex sections were paralleled exactly with the somatosensory cortex's sections. The postcentral gyrus and the postcentral sulcus, which are part of the somatosensory cortex, were also segmented in the same fashion to counterpart with the central sulcus in equal sections. However, the postcentral sulcus was parcellated in only eight, instead of ten, sections due to its small length extension. Lastly, the secondary somatosensory cortex (SII) was defined as the subcentral section lateroventral to the postcentral gyrus on the operculum Rolandi (putative area 43) Sections were limited anteriorly by a line connecting the most anterior point of the prefrontal superior and inferior sulci. Posteriorly, these sections bordered the anterior margin of the inferior and superior precentral sulci. In addition, a line perpendicular to the three folding structures was drawn in the exact middle of their extension to define anterior and posterior sections.The latero-frontal cortex was parcellated in seven sections. Four sections along the frontal middle and inferior gyri and sulci anterior to the DLPFC, as well as three sections defined by the orbital gyrus and sulcus and the frontomarginal gyrus.The cingulate sulcus and gyrus were subdivided in three and four different sections respectively. They were labeled in an antero-posterior order extending between a horizontal line drawn from the most antero-inferior point of the corpus callosum (rostrum) to include the marginal ramus of the cingulate sulcus for the cingulate sulcus, and to the most inferior point of the splenium of the corpus callosum in the cingulated gyrus.Anterior Fissure Lateral (lf1) and the Posterior Fissure Lateral (lf2) sections. The proper insular sections are included along the insular gyrus, which abuts the inferior and superior sulci. Posteriorly they border the lf1 sections, and anteriorly a vertical line connecting the most anterior point of the inferior and superior sulci. A perpendicular line crossing at mid point of the three folding insular structures consequently defining the anterior and posterior sections.The insula was parcellated manually and individually in eight sections along the lateral fissure lateral, superior insular sulcus, insular gyrus, and inferior insular sulcus. The fissure lateral was delimited posteriorly by the gyrus parietal inferior, anteriorly by the insular gyrus and inferior and superior sulci, and ultimately divided in two sections. These two sections were defined by a perpendicular line crossing the exact midpoint of the fissure lateral, which gave rise to the i with the age of subject Ai as a covariate. If Τi denotes the cortical thickness value in a particular ROI from subject i, then the GLM model is:2) is the normally distributed random error. The model was fit repeatedly with various subsets of the three regressors viz., mean effect, duration, and age. A best subset was found using stepwise elimination. Once the best model was defined, t tests were carried out to test the significance of the model coefficients. We carried out a similar analysis using the positive zstats, negative zstats and the ratio of positively activated voxels to negatively activated voxels in place of the cortical thickness Τi in equation (1).Given a set of m subjects, the goal was to compare the cortical thickness values for various regions of interest across subjects and assess the influence of duration of pain YIn addition, Multivariate Pairwise Correlations were done with the multiple cortical thickness values, as well as those values and clinical variables (other than disease duration), including: age-at-onset, VAS for pain intensity and Beck depression inventory (BDI) ratings Results for functional imaging have been previously reported . In reporting results for BOLD signal changes we use deactivation for decreased or negative BOLD signal, and activation for increased or positive BOLD signal. In what follows we use TNP for ‘trigeminal neuropathic pain’ and HC for healthy controls. and supplementary Using automated When the TNP cohort was compared to the HC, we observed bilateral thinning in the lowest sections of the somatosensory cortex that somatotopically represents the craniofacial region in SI  was significantly thicker bilaterally in TNP patients when compared to HC . The thickening in the ipsilateral section 4/5 was also spatially concurrent with BOLD deactivation during brush stimulation of allodynic V2. Other more rostral somatotopic regions in SI bilaterally that represent lower quadrants of the body (sections 7 and 8) were also significantly thicker in TNP patients, however they were only adjacent to BOLD deactivation during the allodynic brush stimulation applied to the affected V2 area  and is located anterior to the central sulcus (putative BA 4). Although no thickness changes between TNP and HC were noticed in the craniofacial sections (1 and 2) of the precentral gyrus, we observed significant thinning in sections (3 and 4) that may represent the hand When the TNP group was compared with the HC group, we found significant bilateral thinning in ventral DLPFC , mainly along the anterior and posterior frontal inferior sulci , which extended to the dorsal DLPFC in the contralateral side to the pain (p<0.011). These findings were spatially colocalized with sparse BOLD activations and deactivations.When compared to the HC group the TNP group showed significant bilateral thinning in the frontal middle gyri that extended to the correspondent sulci (putative BA 10) (Cingulate Cortex Sulcus 1 to 3 as well as Cingulate Cortex Gyrus 1 to 4. The mid-cingulate sulcus showed significant thinning (postulated BA 24/31) (The cingulate cortex was labeled in the following antero-posterior order see : CingulaSignificant (p<0.001) cortical thickening was seen in the posterior insula  contralateral to the neuropathic pain in TNP patients when compared to the HC group. This thickening was spatially colocalized with BOLD activation following allodynic activation  as a control ROI. We made this choice based on the notion that there is little or no evidence for the occipital regions to have any significant role in neuropathic pain. The Occipital Middle Sulcus (OMS) showed no significant differences between TNP and HC cohort .In order to define whether the structural cortical changes studied in our patient cohort are specific to the pain-related cortical ROIs or simply a general phenomenon across the cortical mantle, we have chosen the As summarized in Significant correlation was found between the duration of the disorder and the activation and deactivation absolute signal Z-values. Hence, TNP invariably lead to larger deactivation with time. Positive correlation of duration with activation was found in the following cluster-ROIs: ipsilateral anterior (p<0.009), as well as contralateral medial (p<0.04) and posterior (p<0.04) cingulate cortices; bilateral ventral DLPFC , and contralateral dorsal DLPFC (p<0.03); and bilateral fronto-polar cortices . Positive correlation with deactivation - ipsilateral somatosensory cortex that represents the hand area (p<0.05); contralateral medial cingulate cortex (p<0.04); ipsilateral medial insula (p<0.05); and contralateral fronto-polar cortex (p<0.01). The positive correlations of duration with activation always coincided with thinning in the cortical ROIs of TNP patients when compared to controls. We found mixed results, thickening/thinning, when we looked at the ROIs with positive correlation with deactivation. Nonetheless, when duration was correlated alone with deactivation there was cortical thickening in the ROI, which was the case of SI-hand and medial insula.There was a positive correlation of duration in the contralateral medial cingulate cortex (p<0.05) and the bilateral fronto-polar cortices  with the ratio between number of voxels activated (positive) and deactivated (negative) during allodynic stimulation. This means that with time there is either an increase in the number of voxels activated or a decrease in the voxels deactivated in those ROIs in patients with TNP.There was a negative correlation between the duration in years of the TNP and the thickness in the ipsilateral fronto-polar cortical area of allodynic activation. It means the longer the pain disorder the thinner the fronto-polar cortex is (p<0.05). In the anterior insular cortex contralateral to the pain there was a positive correlation between cortical thickness and the duration of the disorder (p<0.04), which does not corroborate with the general results since this ROI showed thinning when compared to healthy controls.There was a significant positive correlation with the cortical thickness of the contralateral SI, the posterior insula (PINSC) and the most dorsal region of the DLPFC (DDLPFC) . Positive correlations were also found between contralateral frontopolar cortex (FP2C) and ipsilateral medial insula (MINSI) , as well as the ipsilateral orbito-frontal cortex (OFI) and contralateral ventral DLPFC (VDLPFC) . On the contrary, negative correlations were noticed between MINSI and VDLPFC , and FP2C and ipsilateral frontopolar cortex (FPI) .Negative correlation was detected between age-at-onset of the disorder and DLPFC thickness  and contralateral dorsal . VAS for pain intensity was positively correlated with the contralateral MCC .Chronic pain is associated with structural and functional changes in the CNS The following regions are considered to be involved in the sensorimotor function: SI, SII, MI, and posterior insula.The primary somatosensory cortex (SI), which corresponds to part of the fundus of the central sulcus and its posterior wall (putative BA 3b/1), is the main cortical region for sensory-discriminative processing Using MRI tools with high spatial resolution for structural measurement The bilateral thickening of rostral neighboring somatotopic areas in SI (hand/truck) contrasted to the thinning observed in the caudal  somatotopic region. Physiologically, there is an axonal bias at the representational body sections of SI, where strength or number of synapses as well as inhibitory and excitatory mechanisms are increased in this restricted sections and decreased across the bordering sections, for instance between the craniofacial and hand regions Significant thinning of the primary motor cortex (MI) sections 3 and 4 contralateral to the neuropathic pain were observed Figure 2We found bilateral cortical thickening in the more posterior regions of the insula Figure 5Recent research on the involvement of non-sensory regions in chronic pain The DLPFC is known for its key role in attention, memory and executive functions, being usually described in neuropsychiatric imaging studies, including goal-directed tasks The cortical thinning in the DLPFC of TNP patients was located in the bilateral anterior and posterior sections of the frontal inferior sulcus and posterior section of the contralateral frontal middle gyrus, which putatively corresponds to ventral and dorsal BA 9/46, respectively. The BA 9/46 are connected with multiple other cortical and subcortical regions including for example the ventrolateral prefrontal, orbitofrontal, SII, insular and cingulate cortices, as well as thalamus Although findings in the DLPFC were mostly bilateral, cortical thinning extended to more dorsal regions on the side contralateral to the neuropathic pain (left hemisphere) (putative 9/46d). A differentiation for a putative role of the right and left DLPFC role in pain perception has been suggested. Activation in the right DLPFC is predominantly seen in pain imaging studies independently of the side of stimulation The etiology of cortical thinning in the DLPFC may be a result of overuse atrophy as a result of chronic stress Most of the neuroimaging studies on the frontal cortex are in the field of neuropsychology, specially processing of reward and punishment reinforcers in situations including decision making We observed thinning in the antero-superior insula contralateral to the neuropathic pain Figure 5anterior CC (ACC) ; medial CC (MCC) (reaction selection); posterior CC (PCC) (self orientation); retrosplenial cortex (RSC) (memory) Changes in the rCBF of the cingulate cortex (CC) have been frequently reported in experimental and clinical pain neuroimaging studies, mainly in its anterior portion per seWe found cortical thinning of the medial sulcal region of the CC contralateral to the TNP that nearly corresponds to the posterior subdivision of the MCC (pMCC)  Figure 4Thickening was also observed in the anterior sulcal portion of the MCC (aMCC), a region that interacts not only with the motor system, but also with the amygdala The notion of thickening or thinning in different parts of the cortex suggests compensation in response to an initial or persistent insult that results in neural instability. Clinically there is a continual barrage of activity that acts on systems that are considered to be hypersensitized . Duration, age-at-onset and severity of the disease may contribute to differences in the magnitude of neuroplastic changes in each individual. As the exploratory analyses done in our study were not corrected for multiple comparisons, there is an increased risk for false positives. Nevertheless, our integrative neuroimaging approach illustrated coexistent functional and structural cortical changes that had only been described in humans and animals separately. Future longitudinal studies might provide a better dynamic picture of the neuroplastic changes discussed.A number of caveats should be considered in this present study: (1) Number of subjects: In order to select a precisely matched group of trigeminal neuropathic pain patients with pain in the same side, location and branch of the nerve affected, as well as similar pain ratings, from a cohort of 31 screened by phone and medical examination, only six patients were recruited. They all were also right-handed. Furthermore, each patient was scanned twice and the data was averaged. Nonetheless, the magnitude of changes in cortical thickness detected in our study was above what was reported in other studies in the sensorimotor cortex of other neurological conditions Functional and structural neuroimaging approaches were concomitantly used to investigate the consequences of chronic TNP on the cortex of such patients. Our results show that the chronic suffering from trigeminal neuropathic pain leads to gray matter reorganization that occurs at multiple intrinsic cortical systems associated with sensorimotor and cognitive-emotional changes. More specifically, our results suggests that in these patients there is a pattern of mutual cortical changes in neighboring and remote cortical regions associated with pain perception, which mostly colocalizes with the persistent allodynic activity; and second, clinical variables and cortical activity may indeed influence the neuroplastic process that takes place in the brain of those patients. This mal-adaptive remodeling activity may be responsible for the persistence of the illness and sensory-related dysfunction in TNP patients, even when the peripheral and initial cause is treated or removed. These changes may account for the resistance various treatment options in neuropathic pain. Taken together, these changes may provide useful markers for measures of therapeutic interventions.Data S1(0.02 MB DOC)Click here for additional data file.Data S2(0.05 MB DOC)Click here for additional data file.


The need for early ambulation for caring of the neonate by mothers makes postoperative pain management after cesarean delivery unique. Favorable results have been observed with buprenorphine, clonidine and bupivacaine as epidural analgesics. This prospective, randomised triple blind control study was carried out among 112 lower segment caesarean segment (LSCS) patients, divided into three groups, to assess the analgesic efficacy and side effects of epidural analgesia, with an intermittent top up of (i) bupivacaine (0.125%) and buprenorphine (0.075 mg) (ii) bupivacaine (0.125%) and clonidine (37.5 microgram) and (iii) bupivacaine (0.125%) alone, in LSCS cases. The demographic characteristics  of the three groups were comparable and the differences were not statistically significant. The mean duration of the analgesia was significantly longer in the group one patients receiving buprenorphine plus bupivacaine (690 ± 35 minutes) and it was lowest in group three patients receiving bupivacaine (170 ± 31 minutes) alone. The mean highest pain score  was significantly lower (3.4 ± 0.6) in group one patients and it was highest in group three (6.7 ± 0.8) patients. Requirement of continuation of epidural analgesia after 15 hours of operation and requirement of diclonfenac injections as well as incidence of itching and pruritus was significantly lower in group one patients. Incidence of nausea and vomiting was the lowest in group one patients. Incidence of respiratory depression, sedation and hypotension were nil in all three group of patients. Epidural buprenorphine combined with bupivacaine produced significantly longer duration and better quality of analgesia than bupivacaine combined with clonidine or bupivacaine alone, and it was safe in LSCS patients, for post-operative analgesia. The need for early ambulation for caring of the neonate, by mothers, makes postoperative pain management after caesarean delivery unique. To achieve this, various drug combinations and techniques have been tried, to find out the more effective and safer analgesia. Favourable results have been observed with buprenorphine as an analgesic.2 Bupreno4This study was conducted in a hospital of Uttar Pradesh (UP). It was designed in the form of a prospective, randomized and triple-blinded study. Approval for the study was obtained from the institutional ethical committee and a written informed consent from each patient was taken before the study. The postoperative Visual Analogue Scale (VAS) score was considered to be the primary end point in the determination of sample size. It was determined that a sample size of 36 patients in each group would have 80% power to detect 30% difference in VAS, while limiting the type I error to less than 5%. One hundred and twelve patients at term (ASA-I and ASA-II), scheduled for lower segment caesarean section under epidural anaesthesia, were selected by the simple random sample technique and divided into three groups. Patients with complicated pregnancy, acute foetal distress and history of hypersensitivity to opioids / local anaesthetics were excluded. In the pre-anaesthetic visit, all the patients were made familiar with the study plan and the different visual analogue scales (VAS) to be used in the assessment by the investigators. Respiratory rate, arterial blood pressure, peripheral arterial saturation and heart rate were monitored throughout the peri-operative period.Epidural anaesthesia was used for surgery. Subsequently, the epidural route was used for postoperative analgesia also. Intensity of postoperative pain during the first 24 hours postoperatively was assessed at hourly intervals using a visual analogue pain score; 0 denoted ‘no pain’ while 10 denoted ‘worst pain imaginable’. When the patients were asleep, no VAS assessments were made and a VAS of 0 was given. Group one was scheduled to receive bupivacaine (0.125%) at three-hour intervals and buprenorphine (0.075 mg) at 12-hour intervals or when the pain score was 4 or more, or if the patient requested analgesia (whichever occurred earlier). Group two was scheduled to receive bupivacaine (0.125%) and clonidine (37.5 microgram) at three-hour intervals or when the pain score was 4 or more, or if the patient requested analgesia (whichever occurred earlier). Group three received bupivacaine (0.125%) alone at three-hour intervals or when the pain score was 4 or more, or if the patient requested analgesia (whichever occurred earlier). The observer assessing pain was kept blinded for the epidural medication. If the VAS score failed to decline at least by the first one, even after 30 minutes of epidural injection, the patient was given an injection of diclofenac sodium 75 mg intramuscularly. Total analgesics required for a 24-hour period was recorded.P value of < 0.05 was considered significant. The observer analyzing the data was kept blind about the groups to avoid bias in analysis and results.The onset of analgesia was defined as the time from injection of the study medication to the first reduction in pain intensity by at least 1 in VAS; and the duration of analgesia was defined as the time between the onset of analgesia and either a return to baseline VAS or the time when additional pain medication was requested, whichever occurred first. The occurrence of nausea and vomiting, pruritus, shivering and respiratory depression (respiratory rate < 12 / minute), and sedation and hypotension was noted for up to 24 hours following administration of the study medication. The collected data was analyzed using the Statistical Package for Social Science . Analysis of variance / Chi square test was used to compare the variables between groups. A A total of 112 patients were studied. Group one and two consisted of 38 patients in each group, while group three consisted of 36 patients. The demographic characteristics  of the three groups as mean, standard deviation and range are depicted in This study has demonstrated that the lower doses of buprenorphine, in addition to bupivacaine, produce a longer duration of analgesia along with lower pain score and lesser requirement of diclonfenac injection in the post-operative period. It prolongs the duration of effective analgesia by a factor of three. Our finding has once again confirmed that a combination of an opioid and a local anaesthetic enhances the onset and prolongs the duration of analgesia more than the opioid or the local anaesthetic alone. Abboud aOur study has demonstrated that buprenorphine produces a better quality of analgesia in terms of the VAS scale. Abboud and coworkers also found a significantly better quality of analgesia in patients receiving epidural bupivacaine with buprenorphine, rather than with bupivacaine alone. A recent study has shown that 2 mg of epidural buprenorphine added to a lower concentration of bupivacaine (0.1%) provided a better quality of labour analgesia in terms of incidence of motor blockade than 0.25% bupivacaine alone. FurthermIn our study, we did not observe itching, pruritus, or respiratory depression in any patient. Other studies of epidural buprenorphine for post-caesarean analgesia were also reported, with either a complete absence or a very low incidence of such side effects. In fact, the prophylactic administration of buprenorphine was recommended for the prevention of such side effects produced by pure agonist opioids such as morphine, and it was also effectively used for the treatment of intractable pruritus associated with dermatological conditions.13 In ourVarious studies have demonstrated that addition of intrathecal clonidine to bupivacaine, even in very small doses, significantly improves the onset and duration of sensory and motor block, with relative haemodynamic stability.–16 In ouLower doses of epidural buprenorphine combined with bupivacaine produce a significantly earlier onset, longer duration and better quality of analgesia than bupivacaine combined with clonidine or bupivacaine alone, and is safe in lower segment caesarean section patients for post-operative analgesia.