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Chronic benign flank pain of unknown etiology presents a significant challenge for pain physicians, especially when interventional treatment options are limited. We report the case of a 26-year-old male with a history of chronic left flank pain, recurrent non-obstructing nephrolithiasis, and a complex urologic background, who was referred to pain management after failing to find relief through previous urologic interventions. Despite the absence of new obstructing stones, the patient's pain persisted. Initial splanchnic nerve blocks using 0.25 % bupivacaine and dexamethasone provided temporary relief, leading to the decision to proceed with pulsed radiofrequency (RF) treatment of the left splanchnic nerves. Under fluoroscopic guidance, the pulsed RF procedure resulted in significant pain reduction, which lasted for four to six months. Over the course of four years, the procedure was repeated six times, providing sustained relief and allowing the patient to resume normal activities, including school and work. This case highlights the potential effectiveness of pulsed RF as a viable option for managing refractory chronic flank pain when other treatments have failed., Competing Interests: The authors declare no financial interests/personal relationships., (© 2025 The Authors.)

Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1β and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1β, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Banik has received book honorarium and not related to this specific topic. The authors declare no other conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: This study investigated if a localized increase in skin temperature in rat models of incisional and inflammatory pain correlates with the intensity of spontaneous and evoked pain behaviors., Methods: Anesthetized rats received either a 20-mm longitudinal incision made through the skin, fascia, and muscle of the plantar hind paw or an injection of complete Freund adjuvant into the plantar hind paw of anesthetized rats to induce local inflammation. Spontaneous and evoked pain behaviors were assessed, and changes in skin temperature were measured using a noncontact infrared thermometer., Results: There were no differences in skin temperature between the ipsilateral and contralateral hind paw before the incision or inflammation. Skin temperature increased at 2 hours after hind paw plantar incision or 1 day after inflammation of the affected paw, which gradually returned to baseline by the first day and fourth days after treatment, respectively. The increase in skin temperature correlated with the intensity of spontaneous pain behaviors and heat but not with mechanical allodynia., Conclusions: Our results suggest that a simple measurement of localized skin temperature using a noncontact infrared thermometer could measure the extent of spontaneous pain behaviors and heat hyperalgesia following plantar incision or inflammation in animals. In the absence of a reliable objective marker of pain, these results are encouraging. However, studies are warranted to validate our results using analgesics and pain-relieving interventions, such as nerve block on skin temperature changes., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Perioperative anaphylaxis is rare but potentially life-threatening. Although the most common causative agents are muscle relaxants and antibiotics, there have been several case reports of sugammadex-induced anaphylactic reactions. Though most cases of perioperative anaphylaxis present after induction, sugammadex anaphylaxis presents at the end of the case, sometimes in unmonitored situations such as after extubation or during transport to the recovery unit. Here we report a case of suspected sugammadex-induced anaphylaxis that led to cardiac arrest. We emphasize that vigilance is required when a high dose of sugammadex is used for the reversal of neuromuscular blockade., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kadiyala et al.)

Both periodontal disease and diabetes mellitus (DM) are important public health issues. Compared to the non-diabetic counterparts, diabetic patients more often suffer from dental problems, sometimes requiring fixed-dental prosthesis. Gingival inflammation and other forms of periodontal disease are the common complications of the dental prosthesis. This prospective comparative experimental study was intended to compare the outcome of the periodontal health after placement of full veneer crown in diabetic and non-diabetic patients in the Department of Prosthodontics, Faculty of Dentistry, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh from April 2018 to March 2019. This study involved consecutive 53 diabetic and 53 non-diabetic adult patients of either sex, undergoing treatment with full veneer crown in either maxillary or mandibular posterior teeth with healthy periodontal tissue. The outcome variables were: plaque index, gingival index, periodontal pocket depth, and bleeding on probing, at baseline, 3 months and 6 months post-procedure. Gingival index in the diabetic group reached from 0 at baseline to nearly 0.1 at 3 months which then steeply reached to 0.2 at 6 months interval, whereas the same index in the non-diabetic group reached from 0 at baseline to 0.009 at 3 months and 0.04 at 6 months interval. Plaque index of diabetic patients increased from 0 at baseline to 0.5 at 3- and 6-months interval, whereas the plaque index of non-diabetic patients increased to 0.4 at 3 months and then decreased again 0.3 at 6 months interval (p<0.001). Periodontal pocket depth of diabetic group increased from 1.0mm at baseline to 1.2 and 1.5mm at 3 and 6 months respectively, while the same measure in the non-diabetic group increased to 1.1 and 1.3mm at 3 and 6 months respectively (p<0.001). Bleeding on probing index in the diabetic group reached sharply to 1.5 at 3 months from 0 at baseline and then it reached 2.3 at 6 months, whereas the same index in non-diabetic group reached 1.1 and 1.6 at 3 and 6 months respectively (p<0.001). Periodontal health outcome of full veener crown in diabetic patients is adversely affected compared to that in non-diabetic patients.

Methylene blue (MB) is an effective treatment for methemoglobinemia, ifosfamide-induced encephalopathy, cyanide poisoning, and refractory vasoplegia. However, clinical case reports and preclinical studies indicate potentially neurotoxic activity of MB at certain concentrations. The exact mechanisms of MB neurotoxicity are not known, and while the effects of MB on neuronal tissue from different brain regions and myenteric ganglia have been examined, its effects on primary afferent neurons from dorsal root ganglia (DRG) have not been studied. Mouse DRG were exposed to MB (0.3-10 μM) in vitro to assess neurite outgrowth. Increasing concentrations of MB (0.3-10 μM) were associated with neurotoxicity as shown by a substantial loss of cells with neurite formation, particularly at 10 μM. In parallel experiments, cultured rat DRG neurons were treated with MB (100 μM) to examine how MB affects electrical membrane properties of small-diameter sensory neurons. MB decreased peak inward and outward current densities, decreased action potential amplitude, overshoot, afterhyperpolarization, increased action potential rise time, and decreased action potential firing in response to current stimulation. MB induced dose-dependent toxicity in peripheral neurons, in vitro . These findings are consistent with studies in brain and myenteric ganglion neurons showing increased neuronal loss and altered membrane electrical properties after MB application. Further research is needed to parse out the toxicity profile for MB to minimize damage to neuronal structures and reduce side effects in clinical settings.

Among anesthesia-related life-threatening complications, respiratory failure requiring reintubation is common. However, studies evaluating patient characteristics for extubation failure are scarce in the literature. Such knowledge is important to increase awareness and for the development of strategies to improve the safety of anesthesia care. We retrospectively reviewed 196 cases that were reported to our quality assurance (QA) committee from 2004 to 2014 at 3 hospitals. The reintubation rate was 0.09% (n=196). More reintubations occurred in the operating room than the postanesthesia care unit (58% vs 30%). Ninety-three reintubated patients (47%) were 65 years or older. Most patients were in ASA class 3 or 4 (76%) and had a surgical procedure lasting longer than 3 hours. Eleven reintubated patients (5%) died during the hospital course. The exact causes of reintubation could not be determined because of limited data in our QA database. We conclude that although the individual risk of reintubation for each patient is low, the reintubated patients have a higher mortality rate. The study findings emphasize the need for extra vigilance before anesthesia providers attempt extubation of a patient who is elderly, underwent surgery over 3 hours, has chronic obstructive airway disease, or has ASA class 3 or 4 status., Competing Interests: Name: Ratan K. Banik, MD, PhD Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: Partly supported by the Department of Anesthesiology, University of Minnesota. Name: Kate Honeyfield, BA Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: Partly supported by the Department of Anesthesiology, University of Minnesota. Name: Sana Qureshi, MD Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: Partly supported by the Department of Anesthesiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York. Name: Shamantha G. Reddy, MD, FASA Contribution: This author made significant contributions to the conception, synthesis, writing, and final editing and approval of the manuscript to justify inclusion as an author. Disclosures: Partly supported by the Department of Anesthesiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York. The authors did not discuss off-label use within the article. Disclosure statements are available for viewing upon request., (Copyright © by the American Association of Nurse Anesthetists.)

Background: Modern intrathecal drug delivery systems (IDDS) are technologically advanced to deliver medication through various automated and patient-controlled programs. They also are associated with unique complications ranging from post-operative complications, medication-related adverse events (AE), device malfunction, to refill associated AE., Objectives: To systematically analyze real-world complications and AE reported on the Food and Drug Administration's Manufacturer and User Facility Device Experience database (MAUDE) associated with IDDS among patients predominantly with chronic pain disorders., Materials and Methods: MAUDE database was sampled for a month four times a year during the study period, February 2018 to February 2019. The database was resampled every six months till August 2020 to evaluate for any additional reported cases during the index months. The two FDA approved IDDS, were included. AE were broadly classified into causes related to catheter malfunction, pump malfunction, biologic, and medication-related AE., Results: A total of 1001 reports were included in the final analysis. The top three reasons for adverse report are infection/erosion (15.7%, n = 157), motor stall (12.4%, n = 125) and adverse medication reactions (11.8%, n = 119), respectively. There were five deaths among patients with IDDS. Epidural hematoma (n = 3) after IDDS surgery resulted in a death and residual neurological deficits after surgical evacuation. Programming errors, medication concentration discrepancy, and failure to turn on the pump after reprogramming are various preventable causes of medication-related IDDS AEs., Conclusions: Analysis of AE associated with IDDS from the MAUDE database provided a real-world perspective different from reported registry complications. Awareness and vigilance of preventable IDDS-related complications is the first step toward mitigating risks to provide safe and effective intrathecal drug delivery for chronic pain management., (© 2020 International Neuromodulation Society.)

Objective: To analyze industry payments to pain medicine physicians in the United States., Design: Retrospective cohort study using publicly available databases., Subjects: The study includes U.S. pain medicine physicians (PMPs) with reports in the Open Payments program from 2013 to 2018., Methods: The Centers for Medicare and Medicaid Services Open Payments program was analyzed for general, investment, and ownership payments to PMPs reported from 2013 to 2018. The nature, type, and geographic variation of payments were analyzed., Results: The main findings of the study are as follows: 1) Payments made to PMPs constituted a small proportion of the payments made to all physicians in the United States, and the number of transactions and the total dollar amount seem to have decreased from 2016 to 2018. 2) The median number of payments among physicians with reported payments was around 4 (interquartile range: 18), and the majority of them were under $20. 3) The majority of payments were for in-kind items and services (85%) and were made for food and beverages (91%), travel and lodging (5.5%). 4) Some of the ownership and investment interest payments exceeded $500,000. 5) The top five drugs associated with physician payments included medications with opioids. 6) A very small minority of payments were made for entertainment or gifts. 7) A third of PMPs with reports had payments reported under more than one taxonomy., Conclusions: Overall payments made to PMPs seem to be decreasing since 2016. The majority of the payments are made for the food, beverage, and travel categories. Public and physician awareness of the Open Payments system reports is essential to promote transparency and to minimize adverse effects of financial relationships on patient care., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Pancreaticobiliary diseases are the important causes of morbidity and mortality worldwide. Among the imaging modalities, Transabdominal ultrasound (TUS) is cheap, available, and noninvasive but it has some limitations. Endoscopic ultrasound (EUS) is invasive but it has some diagnostic and therapeutic advantages over TUS. This study was aimed to see the diagnostic yields of EUS and TUS in the pancreatobiliary diseases. This cross sectional study was conducted in Sir Salimullah Medical College Mitford Hospital (SSMC&MH), Dhaka, Bangladesh from March 2017 to February 2019. All (n=222) patients were evaluated clinically and with relevant investigations. TUS and EUS were done in all patients. Endoscopic retrograde cholangiopancreatography (ERCP) was done in 60 patients. Among 222 patients 56.8% were males; mean age was 46±16 years; the main presenting symptoms were abdominal pain and jaundice. In diseases of biliary tree, EUS showed dilated CBD alone or in combination with stone in 50 and 67 cases and TUS showed 37, 63 patients respectively. The difference between the findings of EUS and TUS was statistically significant (p=0.00). In gall bladder, EUS found microlithiasis in 6(2.6%) and sludges in 24(10.8%) cases whereas TUS found microlithiasis in 1(0.5%) and sludges in 17(7.7%) cases respectively (p=0.00). Both EUS and TUS detected cholelithiasis in equal number of patients 46(20.3%). On pancreatic evaluation, EUS and TUS detected pancreatic parenchymal abnormalities in 24(10.8%) and 12(5.5%) patients respectively with significant p value (0.00). In cases of pancreatic and cholangiocarcinoma the difference between the findings of EUS and TUS were statistically significant (p<0.05). EUS detected 7 cases of ampullary/peri-ampullary neoplasms whereas TUS detected only 2 cases. The sensitivity of EUS for detecting CBD dilatation, CBD stones, CBD SOL and pancreatic SOL was 85%, 91%, 93%, and 92% respectively. The sensitivity of TUS for detecting CBD dilatation, CBD stones, CBD SOL and pancreatic SOL was 42%, 52%, 40%, and 37% respectively. EUS is more sensitive than TUS in diagnosing pancreaticobiliary disorders. It is of paramount importance in patients in diagnosing CBD dilatation, choledocholithiasis, biliary microlithiasis and pancreaticobiliary neoplasm. EUS has important role before proceeding to further management by more invasive techniques like ERCP or surgery.

Objectives: Chronic pain spinal implantable electronic devices (CPSIEDs) include devices that provide spinal cord stimulation and intrathecal drug therapy. In this study, we sought to evaluate the trends of CPSIED infections, related complications, and outcomes following the treatment of infection., Materials and Methods: The Nationwide Inpatient Sample database contains data from 48 states, and the District of Columbia was used to identify patients with a primary diagnosis of CPSIED infection during the years 2005-2014. Patients with intrathecal pumps for the treatment of spasticity were excluded to limit the study population to patients with chronic pain disorders. Treatments were categorized as: 1) without device removal, 2) pulse generator or pump only removal, 3) intrathecal pump system removal, and 4) spinal cord stimulation system removal. Complications associated with CPSIED infections were identified using administrative billing codes., Results: During the study period 2005-2014, a total of 11,041 patients were admitted to the hospital with CPSIED infections. The majority of the patients were treated without surgical intervention (56%), and a smaller proportion underwent complete system explantation (22.7%). In-hospital mortality or permanent disability due to paralysis after CPSIED infection was around 1.83% and 2.77%, respectively. Infectious complications such as meningitis, abscess formation, and osteomyelitis occurred in 4.93%, 5.08%, and 1.5%, respectively. The median cost of hospitalization was around US $14,118.00, and the median length of stay was approximately six days (interquartile range = 4-13 days)., Conclusions: The complications of CPSIED infection were higher among patients that did not undergo device removal., (© 2020 International Neuromodulation Society.)

MICRA, miniaturized leadless single chamber pacemaker, is inserted directly into the right ventricular myocardium via transcatheter approach. We present a case of a 66-year-old patient with a Micra pacemaker scheduled for kidney-pancreas transplant. The patient is pacemaker dependent. The preoperative cardiology consult did not comment on the need of reprogramming. One hour prior to the surgery, the anesthesia team was unable to locate the pacemaker on the chest wall. The Medtronic hotline was called, and the caregivers learned that the particular pacemaker is buried within the ventricular wall and is not responsive to an external magnet. Thus, the case was delayed and a cardiac electrophysiology team was contacted to reprogram the pacemaker to VOO (fixed ventricular pacing) mode. We suggest that the pacemaker can pose perioperative challenges due to its novelty, paucity of report, and guidelines., Competing Interests: None

We present a case of a 30-year-old female, who had tracheostomy revision complicated by false passage into the subcutaneous space and pneumothorax. Six days later, she developed massive bleeding from the mouth, nose, and tracheostomy site. Approximately 2 liters of blood was lost. With high suspicion for tracheo-innominate fistula, she was emergently brought to the operating room for fistula repair. Her anesthetic management was initially focused on maintaining spontaneous ventilation with inhalation agents until surgical exposure was adequate. An endotracheal tube was then placed under guidance of a video-laryngoscope. The tracheostomy tube was then removed over a Cook catheter to maintain secure passage in case of airway collapse. The oral endotracheal tube was then inserted distal to the arterial and tracheal defect. The patient's bleeding was stopped, the fistula was repaired, and she was transferred back to the intensive care unit, but she died several days later due to multi-organ failure., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Vinayak Nadar and Ratan K. Banik.)

Background: Spontaneous pain after surgical incision is a significant problem for most post-operative patients. Pain management that relies on opioids is hindered by numerous side effects, fuelling interest in non-opioid alternatives and multimodal approaches. Subcutaneous capsaicin infiltration has shown potential for reducing post-operative pain, but there are unanswered questions about safety and possible side effects. In adult rats, we characterized the analgesic effects of pre-operative capsaicin infiltration into the skin prior to plantar incision and assessed wound healing and epidermal innervation., Methods: The surgical site on the plantar surface of the rat hind paw was infiltrated with 1% capsaicin or vehicle 30 min or 1 week prior to surgical incision. Spontaneous and evoked pain behaviours were assessed. Digital images of incised hind paws were used to quantify the surface area of the wound after suture removal. Epidermal nerve fibre quantification was performed on peri-incisional tissue biopsies., Results: Intraplantar administration of capsaicin 30 min before surgical incision attenuated spontaneous pain behaviours, heat hyperalgesia, epidermal innervation, but it did not alter the rate of wound healing. Incisional pain hypersensitivity returned to baseline 2 weeks post-incision, at a time when no recovery of epidermal innervation is observed., Conclusions: Subcutaneous infiltration of capsaicin prior to surgical incision attenuated incision-induced pain behaviours and reduced epidermal innervation around the incision site. The long-lasting epidermal denervation by capsaicin had no impact in the rate of wound healing and recovery from pain behaviours., Significance: Pre-operative capsaicin infiltration attenuated spontaneous pain-like behaviour and prevented the development of heat hyperalgesia following plantar skin incision. While capsaicin caused long-lasting and widespread loss of epidermal and dermal nerve fibres, there was no measurable impact on the rate of wound healing. Pre- or intra-operative infiltration of capsaicin into surgical sites could act as a safe prophylactic for post-operative pain and reduce the need for opioids during recovery., (© 2020 European Pain Federation - EFIC®.)

To develop non-opioid therapies for postoperative incisional pain, we must understand its underlying molecular mechanisms. In this study, we assessed global gene expression changes in dorsal root ganglia neurons in a model of incisional pain to identify pertinent molecular pathways. Male, Sprague-Dawley rats underwent infiltration of 1% capsaicin or vehicle into the plantar hind paw (n = 6-9/group) 30 min before plantar incision. Twenty-four hours after incision or sham (control) surgery, lumbar L4-L6 dorsal root ganglias were collected from rats pretreated with vehicle or capsaicin. RNA was isolated and sequenced by next generation sequencing. The genes were then annotated to functional networks using a knowledge-based database, Ingenuity Pathway Analysis. In rats pretreated with vehicle, plantar incision caused robust hyperalgesia, up-regulated 36 genes and downregulated 90 genes in dorsal root ganglias one day after plantar incision. Capsaicin pretreatment attenuated pain behaviors, caused localized denervation of the dermis and epidermis, and prevented the incision-induced changes in 99 of 126 genes. The pathway analyses showed altered gene networks related to increased pro-inflammatory and decreased anti-inflammatory responses in dorsal root ganglias. Insulin-like growth factor signaling was identified as one of the major gene networks involved in the development of incisional pain. Expression of insulin-like growth factor -2 and IGFBP6 in dorsal root ganglia were independently validated with quantitative real-time polymerase chain reaction. We discovered a distinct subset of dorsal root ganglia genes and three key signaling pathways that are altered 24 h after plantar incision but are unchanged when incision was made after capsaicin infiltration in the skin. Further exploration of molecular mechanisms of incisional pain may yield novel therapeutic targets.

Gastroesophageal reflux disease is widely reported most prevalent disease of the gastrointestinal tract. The burden of gastroesophageal reflux disease (GERD) is increasing in Asia and the majority of patients have non-erosive reflux disease. This prospective, open label, non random (consecutive), experimental study was performed due to compare the therapeutic efficacy of alginate and omeprazole in relieving symptoms of non erosive reflux disease (NERD) and was carried out in the Outpatient Department of Gastroenterology, Dhaka Medical College Hospital, Dhaka, Bangladesh from December 2013 to May 2014. Sixty patients were enrolled for this study and were divided into two groups. Among them, 30 subjects were assigned to the omeprazole group (Group I) and 30 subjects to the alginate group (Group II). Omeprazole 20mg enteric coated capsule daily and alginate 10ml three times daily were administered 14 days in this study. In ITT analysis, achieving complete symptom relief (heart burn) was 56.7% in alginate group & 60% in omeprazole group. Statistically which was not significant (p=0.793). In PP analysis, this was 65.4% and 66.7% respectively. In this study, the overall satisfaction of omeprazole & alginate was more than 86% and the mean duration of heart burn free was found 5.0±4.0 days in Group I and 3.65±2.8 days in Group II. The difference was not statistically (p>0.05) significant between two groups in this study. Therapeutic efficacy and safety profiles of alginate were comparable to omeprazole after two weeks treatment in NERD subjects. So alginate may be considered as a relevant and effective alternative medication in non-erosive reflux.

Peripheral nerve stimulation has been used in the treatment of several chronic pain conditions including pain due to peripheral nerve dysfunctions, complex regional pain syndrome, and cranial neuralgias. It has been shown to be effective for chronic, intractable pain that is refractory to conventional therapies such as physical therapy, medications, transcutaneous electrical stimulations, and nerve blocks. Recently, a new generation of peripheral nerve stimulation devices has been developed; these allow external pulse generators to transmit impulses wirelessly to the implanted electrode, and their implantation is significantly less invasive. In this review, we discuss the history, pathophysiology, indications, implantation process, and outcomes of employing peripheral nerve stimulation to treat chronic pain conditions.

The under-reporting of pain and atypical manifestations of painful syndromes within the elderly population have been well documented, however, the specific relationship between pain and aging remains ambiguous. Previous studies have reported degenerative changes in primary afferents with aging. In this study, we questioned whether there is any change in the density of primary afferent endings within the epidermis of aged animals. Rats were categorically assessed in 4 age groups, each representing a key developmental stage across their life span: juvenile (2 months), adult (7 months); aged (18 months), and senescent (24-26 months). The plantar hind paw skin was removed, post-fixed, cut, and immunostained for protein gene product 9.5 and type IV collagen. Rats in the adult aged groups had significantly increased epidermal nerve densities and total lengths of immunoreactive nerve fibers, compared with juvenile as well as senescent rats. However, the paw withdrawal thresholds to punctate mechanical stimulation progressively increased with age, and did not exhibit a clear relationship with epidermal innervation. We conclude a nonlinear, inverted-U shaped relationship between rat plantar epidermal nerve density with aging, which does not correlate with mechanically-induced paw withdrawal behaviors., Perspective: This article presents age-related decreased epidermal innervation in rat hind paw skin, which partly explains mechanisms underlying decreased pain sensitivity in aged subjects. The report may help clinicians to understand that any compromise of pain-sensing pathway can lead to under-reporting of pain, inadequate analgesia, and slower recovery from a painful condition., (Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the world. This study was carried out to see the epidemiological and clinicopathological profile of sporadic cases of CRC in Bangladesh., Materials and Methods: The patients diagnosed to have colorectal carcinoma in two private medical centers of Bangladesh from January 2012 to December 2014 were enrolled in this study. Demographic data, clinical presentations, site of lesions, and histological types were analyzed., Results: Total 158 patients were included in this study. The mean age was 50.77 years and male to female ratio was 1.55:1. Rectal bleeding was the commonest symptom irrespective of age and sex followed by abdominal pain (33, 20.9%), weight loss (29, 18.3%), abdominal mass (26, 16.4%), and altered bowel habit (22, 13.9%). Common histological type was adenocarcinoma (156, 98.7%)., Conclusion: Colorectal cancer commonly affects males >40 years of age. Most common site of involvement is rectum, which is followed by left colon., How to Cite This Article: Saha M, Shil BC, Saha SK, Banik RK, Perveen I, Chowdhury MKS, Nazmul Islam ASM, Saifullah ANM. Study of Clinicopathological Profile of Sporadic Cases of Colorectal Cancer. Euroasian J Hepato-Gastroenterol 2016;6(2):134-136., Competing Interests: Source of support: Nil Conflict of interest: None

Aims: To see the prevalence of lactose intolerance (LI) and related symptoms following oral lactose challenge in healthy volunteers., Materials and Methods: Symptoms of abdominal pain, nausea, borborygmi, flatulence, and diarrhea were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 25 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥ 1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM), i.e., LI., Results: A total of 166 volunteers (123 males, 43 females) with a mean age 34.78 ± 11.45 years participated in this study. Lactose intolerance was found among 85.54% (n = 142, M = 104, F = 38). The main symptoms of LI were diarrhea (n = 83, 58.4.0%), borborygmi (n = 81, 57.04%), abdominal pain (n = 35, 24.65%), and flatulence (n = 27, 19.0%)., Conclusion: Lactose intolerance among healthy adults may be common in Bangladesh. Diarrhea and borborygmi were mostly associated symptoms of LI., How to Cite This Article: Saha M, Parveen I, Shil BC, Saha SK, Banik RK, Majumder M, Salam MU, Nazmul Islam ASM. Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers. Euroasian J Hepato-Gastroenterol 2016;6(1):5-7., Competing Interests: Source of support: Nil Conflict of interest: None

Background: Unrelieved acute postoperative pain can lead to a wide range of adverse effects, such as anxiety, depression, restlessness and sleep deprivation., Objective: To investigate anxiety-like behaviour in a postoperative pain model., Interventions and Main Outcome Measures: Mechanical hypersensitivity was assessed with an electronic von Frey device, whereas anxiety-like behaviour was measured with light/dark testing and elevated plus maze testing., Results: Rats developed significant mechanical hyperalgesia on 1, 3 and 8 days postsurgery compared with sham-operated rats. There was no reduction in motility between preincision and postincision when animals were allowed to move freely in an open field locomotion test. In light-dark tests, incised animals spent significantly less time than sham rats in the light compartment on the 1st and 3rd postoperative days. However, in an elevated plus maze test, differences between sham and incised rats were only observed on the 8th postoperative day as they spent significantly more time in the open arms. Pretreatment with morphine significantly increased withdrawal thresholds compared with treatment with saline (0.9% NaCl), but had no effect on light or open arm avoidance behaviour., Conclusion: We report that a rat model of acute postoperative pain is associated with anxiety-like increased light and open arm avoidance behaviour.

Since its introduction in early 1990s, endoscopic ultrasound (EUS) has become integral to the diagnosis and staging of various luminal, extraluminal gastrointestinal (GI) and certain non-GI lesions. There is no data on EUS experience in Bangladesh. The aim of this paper is to evaluate the initial recent experience and clinical impact of EUS. All EUS procedures data were recorded prospectively from July 2013 to December 2014. These included patients' demographics, referral details, provisional diagnosis, management plan before and after EUS & indications of procedures. EUS-FNA data recorded included details regarding site, number of passes and histological diagnosis. Two hundred & four EUS procedures were carried out over one and half years. Male female ratio was 1.4:1, mean age was 46.4 ± 20 years. Of these procedures 148 (72.5%) were referrals from physicians and 56 (27.5%) were from surgeons. Most common indications were pancreatobiliary pathologies, esophageal & gastric pathologies. Pancreatobiliary lesions (n = 165, 80.9%) included patients with (A) Benign pathologies: Microliths in Gall baldder (n = 6), Gall stones (n = 12), Biliary ascarrisis (n = 22), Choledocholithiasis (n = 42), Acute Pancreatitis (n = 9), Chronic Pancreatitis (n = 15), Pancreatic pseudocysts(n = 4) (B) Malignant Pathologies : GB Carcinoma (n = 4), Cholangiocarcinoma (n = 29), Ca- pancreas (n = 9), Periampullary carcinoma (n = 12). Esophageal lesion was 9.3% (n = 19) of total procedures. Forty seven percent (n = 9) of EUS procedures on esophagus were for staging of esophageal malignancy, 10. 5% (n = 2) for restaging or recurrence after chemoradiation and 21% (n = 4) for submucosal lesions. Fifteen EUS procedures were carried out for gastric lesions, seven were for staging of gastric carcinoma, four were for assessment of submucosal lesions (e.g. GIST, lipoma or external compression), 02 for assessment of polyps and two for gastric ulcers.In clinical impact & outcome study, changes in diagnosis, management, avoidance of investigations and usefulness of EUS were evaluated. Diagnosis was changed in 34.4% (64/186) & management was changed in 45%(92/204). Additional investigation was avoided in 57.8% (118/204). This is the first report of Bangladesh experience of EUS to date. EUS is safe, accurate, cost effective & very useful tool for diagnosis and management of G.I. disorders.

Background: Nonevoked spontaneous pain is most problematic for postoperative patients. Physicians assess this form of pain using the human visual analog scale or verbal numeric rating scale. Recent studies have proposed that spontaneous foot-lifting (SFL) behaviors are an expression of spontaneous pain in animals after spinal nerve injury or adjuvant-induced inflammation. In the current study, we characterize SFL behaviors in a rat model of acute postoperative pain, which includes comparisons with evoked behaviors to analgesic treatments., Methods: SFL was manually recorded over four 5-minute periods with 10-minute intervals between each testing session. Paw-withdrawal thresholds were subsequently measured with an electronic von Frey esthesiometer. To evaluate the effects of age, rats were tested in different age groups: 2, 7, and >26 months. The effects of buprenorphine and morphine were tested in a separate group of animals, which received intraperitoneal injections of saline, morphine (0.01, 0.1, 1, or 2 mg/kg), or buprenorphine (0.001, 0.01, or 0.1 mg/kg) before testing., Results: SFL behaviors peaked at 3 hours after incision and significantly recovered by the 3rd or 4th postoperative day (P < 0.0001). The presentation of these behaviors did not significantly vary with animal age (2, 7, and >26 months old; P = 0.30). SFL behaviors, with the exception of rapid SFL at 3 hours after incision, did not show significant correlation with paw-withdrawal threshold behaviors. The median effective dose of buprenorphine for reversal of mechanical hyperalgesia (0.0452 mg/kg; 95% CI, 0.0259-0.0787) was significantly larger than for reversing rapid (0.0027 mg/kg; 95% CI, 0.0009-0.0083; P < 0.0001) and prolonged (0.0004 mg/kg, 95% CI, 0.0000, 0.0035; P = 0.001) SFL at 3 hours after incision. Similarly, the median effective dose of morphine for reversal of mechanical hypersensitivity behaviors (2.901 mg/kg; 95% CI, 1.132-7.436) was larger than for SFL count (0.4044 mg/kg; 95% CI, 0.1048-1.561; P = 0.0103) and SFL duration (0.0309 mg/kg; 95% CI, 0.0095-0.0998; P < 0.0001) at 3 hours after incision., Conclusions: The present study demonstrates that a hindpaw plantar incision induces SFL behaviors in rats and that these behaviors have higher bioassay sensitivity to analgesic interventions with morphine and buprenorphine compared with mechanically evoked behaviors.

Double balloon enteroscopy (DBE) is a newly developed endoscopic modality for diagnosis and treatment of small bowel disorders. The aim of this study was to evaluate the diagnostic and therapeutic impact of DBE in patient with suspected small bowel disease. This was a prospective study. Sixty one double balloon enteroscopy procedures (30 antegrade 31 retrograde) were done in thirty six patients (20M/16F, mean age 40 ± 12.5 range 16-65 years ) at gastroenterology department, Sir Salimullah Medical College, Dhaka between October 2011 and September 2012. Indications for DBE included chronic abdominal pain 14 (38.9%), obscure GI bleeding 11 (30.56%), Small bowel obstruction 05 (13.89%), and chronic diarrhea 06 (16.67%). The morphologic findings were ulcerations 13 (36.11%), growth 03 (8.33%), vascular ectasia 03 (8.33%) and polyp 01 (2.78%). Therapeutic interventions were performed in one patient only. No serious complications were observed. Diagnostic yields in case of chronic abdominal pain, chronic diarrhea, obscure GI bleeding and small bowel obstruction were 50%, 66%, 63% and 40% respectively. The findings were adenocarcinoma 04 (11%), lymphoma 03 (8.4%), tuberculosis 03 (8.4%), non specific findings 05 (13.9%), IPSID 01(2.8%), Crohn's disease 01 (2.8%), vascular ectasia 03 (8.33%) and normal 16 (44.44%). DBE is well tolerated, feasible and useful technique for the diagnosis as well as treatment of small intestinal disorders.

This study describes a modified Hargreaves' method for assessing paw withdrawal threshold temperatures for heat (PWT-H) nociception in the hind paws of rats. This method utilises radiant heat to maintain controlled lamp temperatures (CLTs) on a glass floor beneath the rat hind paw. An ascending series of CLTs were applied for 10s, with 5-10min intervals between applications, until characteristic withdrawal behaviour was observed or a cutoff CLT was reached. The average plantar epicutaneous temperatures measured from anaesthetised rats corresponding to CLTs and withdrawal latencies were used for determining PWT-H. The mean PWT-H in 2-month-old (mo) naïve Sprague-Dawley rats (n=38) was 47.6±0.2°C, which is comparable to the noxious threshold temperature for human glabrous skin (46.5±0.5°C). The PWT-H was consistent between trials and daily assessments over four consecutive days. No significant differences were observed between the PWT-H in 2-, 6- to 8-, and >24-mo F344 rats, but the PWT-H in 1-mo rats was significantly reduced. Three hours following plantar incision, the PWT-H decreased to 37.5±0.2°C, consistent with previous observations of C-fibre afferents from incised glabrous skin firing at 36.7±3.6°C. Parallel testing, using the current method and an electronic von Frey device, illustrated similar degrees of incision-induced hyperalgesia, gradual improvements in hyperalgesia, and reversals induced through morphine and gabapentin. In conclusion, the present method facilitates a comparison of PWT-H using electrophysiological and human psychophysical studies involving thermosensation, and as a behavioural assay identical to von Frey testing, this method also measures the threshold for nociception., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Dilute capsaicin produces a differential effect on incision-related pain behaviors depending upon the test; it reduces heat hyperalgesia and guarding pain but not mechanical hyperalgesia. This suggests that common mechanisms for heat hyperalgesia and guarding pain occur, and distinct mechanisms exist for mechanical hyperalgesia. The purpose of the present study was to evaluate the effect of capsaicin treatment on the activity of cutaneous nociceptors sensitized by incision to understand the mechanisms for the selective action of dilute capsaicin on incisional pain. We compared the effect of 0.05% capsaicin vs. vehicle treatment on pain behaviors after incision and on the activity of nociceptors from these same rats using the in vitro glabrous skin-nerve preparation. Immunohistochemical expression of protein gene product 9.5 (PGP9.5), neurofilament 200, calcitonin gene related peptide (CGRP) and isolectin B4 (IB4) in skin was also evaluated 1 week after 0.05% capsaicin infiltration. Infiltration of 0.05% capsaicin decreased CGRP and IB4/PGP9.5-immunoreactivity of nociceptors in skin. The same dose of capsaicin that inhibited heat hyperalgesia and guarding behavior interfered with chemo- and heat sensitivity of C-fibers. Neither mechanical hyperalgesia nor mechanosensitivity of nociceptors was affected by capsaicin, suggesting that the concentration of capsaicin used in this study did not cause fiber degeneration. These results demonstrate that nociceptors desensitized by capsaicin contribute to heat hyperalgesia and guarding pain after plantar incision. These putative TRPV1-expressing C-fibers are sensitized to heat and acid after incision, and the transduction of heat and chemical stimuli after plantar incision is impaired by dilute capsaicin., (Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Bradykinin is an endogenous nonapeptide known to induce pain and hyperalgesia to heat and mechanical stimulation. Correspondingly, it excites nociceptors in various tissues and sensitizes them to heat, whereas sensitizing effect on the mechanical response of nociceptors is not well established. Protein kinase C and TRPV1 contribute to the sensitizing mechanism of bradykinin to heat. In addition, TRPA1 and other ion channels appear to contribute to excitation caused by bradykinin. Finally, prostaglandins sensitize bradykinin-induced excitation in normal tissues by restoring desensitized responses due to the inhibition of protein kinase A.

TrpV1, the receptor for capsaicin, contributes to nociception in animals but appears to be much more important for signaling increased behavioral sensitivity in the injured state. The current study examined the relationship between the marked reduction in heat hyperalgesia after incision in TrpV1 knockout (KO) mice and the activity of the nociceptors in these same mice. Also, the role of TrpV1 in spontaneous activity (SA) of afferents after incision was examined. Standard teased-fiber techniques were used to record from glabrous skin afferents from incised and control TrpV1 KO and C57Bl6 mice. The loss of TrpV1 had minimal effect on the responses of mechano-heat-sensitive C-fiber afferents in the normal and incised states. However, a different group of heat sensitive afferents, termed unclassified afferents, was sensitized to heat by incision and had markedly reduced sensitization in the TrpV1 KO mice. These unclassified afferents also developed SA after incision, and generally had a lower threshold temperature compared to unclassified afferents without SA. The rate of SA was inversely correlated to the threshold temperature for heat; afferents that exhibited a higher rate of SA had a lower heat threshold. The proportion of unclassified afferents with SA was also reduced in incised TrpV1 KO mice compared to incised C57Bl6 mice. We conclude that a distinct class of afferents outside the mechano-heat-sensitive afferent population likely contributes to heat hypersensitivity after plantar incision. KO of TrpV1 influences SA in these unclassified afferents in incised skin. SA in these afferents is perhaps a manifestation of heat sensitization.

Bradykinin (BK), a major inflammatory mediator, excites and sensitizes nociceptor neurons/fibers, thus evoking pain and hyperalgesia. The cellular signaling mechanisms underlying these actions have remained unsolved, especially in regard to the identity of channels that mediate acute excitation. Here, to clarify the contribution of transient receptor potential vanilloid 1 (TRPV1), a heat-sensitive ion channel, to the BK-evoked nociceptor excitation and pain, we examined the behavioral and physiological BK-responses in TRPV1-deficient (KO) mice. A nocifencive behavior after BK injection (100 pmol/site) into mouse sole was reduced in TRPV1-KO mice compared with wild-type (WT). A higher dose of BK (1 nmol/site), however, induced the response in TRPV1-KO mice indistinguishable from that in the WT. BK-evoked excitation of cutaneous C-fibers in TRPV1-KO mice was comparable to that in WT. BK clearly increased intracellular calcium in cultured dorsal root ganglion (DRG) neurons of TRPV1-KO mice, although the incidence of BK-sensitive neurons was reduced. BK has been reported to activate TRPA1 indirectly, yet a considerable part of BK-sensitive DRG neurons did not respond to a TRPA1 agonist, mustard oil. These results suggest that BK-evoked nociception/nociceptor response would not be simply explained by activation of TRPV1 and A1, and that BK-evoked nociceptor excitation would be mediated by several ionic mechanisms.

In this study, we recorded activity from afferent fibers innervating the mouse plantar skin, the same region evaluated in pain behavior experiments. We compared responses of afferents from incised and unincised hind paw skin. The plantar skin together with attached medial and lateral plantar nerves was dissected until they could be completely removed intact and placed in an organ bath chamber continuously perfused with oxygenated Kreb's solution with the temperature maintained at 32 degrees C. Afferent nerve activities to feedback-controlled mechanical and heat stimuli and cooling were recorded. Eighty-five single Adelta- and C-fiber afferents were recorded, 42 from control and the remainder from incised animals. A greater proportion of C-fibers (11/34) from incised skin had spontaneous activity than in the unincised preparation (2/32). The mechanical thresholds of both Adelta- and C-fiber units were not different between control and incised groups but the responses to suprathreshold mechanical stimulation were increased in low threshold Adelta- and C-fibers. The greatest change in heat sensitivity was apparent when multi-fiber total activity was measured; threshold was reduced, total spikes were greater and the peak discharge frequency was increased. In summary, feedback-controlled stimulation identified mechanical sensitization after incision in an in vitro preparation. Few fibers were excited by cooling. Heat sensitization of primary afferents was more prominent when activities of unclassified afferents are included. The preparation allows us to study afferent function of the same tissue that is examined for in vivo pain behavior assays in mice.

Acutely, nerve growth factor (NGF) exerts profound effects on nociceptive transmission and produces pain and hyperalgesia. In the present study, we sought to determine the tissue levels and role of NGF after a plantar incision. A substantial increase in NGF protein expression occurred in skin 4-h, 1-day and 2-days and 5-days after incision comparing contralateral uninjured skin. Plantar incision did not change NGF levels in the tibial nerve and L4-L6 dorsal root ganglia. The therapeutic effect of a monoclonal antibody against endogenous NGF was evaluated by intraperitoneal administration of a single preoperative dose of anti-NGF. Of three different doses of anti-NGF used, the highest dose 2.8 mg/kg anti-NGF attenuated or almost abolished guarding pain scores at 4-h, 1-day (>80% decrease) and 2-days after incision. This effect is dose dependent in that lower doses (1, 0.1 mg/kg) were effective only at 1-day after incision. Anti-NGF also attenuated heat hyperalgesia at 1-day and 2-days after incision when the highest dose was used. However, treatment by anti-NGF did not affect C-fibers sensitized 1-day after incision in a glabrous skin-tibial nerve in vitro preparation. In conclusion, increased NGF was present in skin after plantar incision. NGF contributes to some incision-induced pain behaviors, guarding and heat hyperalgesia. Anti-NGF did not affect the extent of sensitization of C-fibers observed in vitro.

Nociceptors are excited or sensitized by many inflammatory mediators as well as by elevation of tissue temperature. We have shown that there is a facilitatory synergistic interaction between norepinephrine (NE) and bradykinin (BK) on cutaneous C-fiber nociceptors in normal Lewis rats. These interactions may play an important role in the mechanism of sympathetically maintained pain. In the present experiment, using skin-saphenous nerve in vitro preparations, we tested the effect of NE on the activity of nociceptive fibers and their response to heat in normal Sprague-Dawley rats. For comparison with the previous data on Lewis rats, we also examined the effect of NE on BK response. NE (10(-5) or 10(-6) M) did not excite nociceptive fibers before repeated heat stimuli or BK superfusion (10(-5) or 10(-6) M) to the receptive field. In contrast, after a few applications of heat or BK, NE excited 20-43% of nociceptive fibers to similar magnitudes. We also found that NE sensitized subsequent BK responses, but somewhat unexpectedly that it suppressed subsequent heat responses. This occurred regardless of the presence or absence of NE-induced excitation. These results suggest different mechanisms of NE modification to the BK and heat responses of cutaneous C-fiber nociceptors.

Postoperative pain is characterized by spontaneous pain at the surgical site and increased pain due to movements. To study postoperative pain mechanisms, we investigated discharge properties of mechano-heat sensitive C-fiber afferents innervating the rat glabrous hindpaw skin 1 day after plantar incision. Behaviors indicating spontaneous pain, heat and mechanical hyperalgesia were present 1 day after incision. Recording of afferents using in vitro glabrous skin-nerve preparation showed that more C-fibers from the incision had spontaneous discharge than control rats. The spontaneously discharging fibers from incised rats had lower heat response threshold compared with fibers without spontaneous activity. In all fibers less than 2 mm from the incision, an increased percentage responded to lower temperatures (35-41 degrees C), the mean heat response threshold was 3.1 degrees C less, the stimulus-response function for heat evoked response was shifted to the left and the total number of impulses in response to a 33-48 degrees C heat stimulus was increased. Heat responses of C-fibers more than 2 mm from the incision, however, were not different from control. The mean mechanical response thresholds, measured by a servo force-controlled stimulator, were not different between groups. The total spikes evoked at supra-threshold mechanical stimulation were not increased in afferents from the incision. In conclusion, 1 day after incision, when behaviors indicating spontaneous pain, heat and mechanical hyperalgesia are present, C-fibers close to incision showed spontaneous discharge and sensitization to heat but not to mechanical stimuli, in vitro.

Many inflammatory chemical mediators excite or sensitize nociceptors, which had led some researchers to believe that they may interact with each other to maintain a persistent painful state. We examined how the excitatory mediators norepinephrine (NE) and bradykinin (BK) interact, using single fiber recordings from cutaneous nociceptors. We observed that NE augmented the BK-induced response in both control and adjuvant-inflamed rats in a way different from NE-induced excitation in inflamed animals only. BK also tended to augment the NE-induced response (examined only in inflamed rats). Our results provide the first evidence that BK and NE synergistically interact on nociceptors.