Pancreatic necrosis is among the most frequently encountered local complications of acute pancreatitis and associates with severe disease. Infected pancreatic necrosis further enhances the risk for morbidity and mortality. Pancreatic fluid collections that result from pancreatic necrosis evolve from acute necrotic collections to walled off necrosis and are defined by their distinct characteristics on cross sectional imaging. A variety of interventions spanning multiple disciplines are available for the drainage and debridement of pancreatic necrosis. Prospective, randomized trials have identified management strategies that incorporate minimally invasive interventions as having the best outcomes for patients with symptomatic pancreatic necrosis. The scientific literature has confidently positioned endoscopic drainage and necrosectomy among the most effective interventions for patients with symptomatic walled off necrosis. Innovations such as the use of metallic stents, chemical debridement and multiple modalities for drainage of pancreatic necrosis show promise in improving outcomes for patients managed with endoscopic interventions.

Background: In the literature, there have been debates as to whether smartphone use has negative effects on physical and mental health. The present study investigated the extent to which smartphone addiction impacts on musculoskeletal pain prevalence among university students.
Methods: The questionnaire consisted of three sections: demographic information, the Smartphone Addiction Scale (SAS), and the modified Nordic Musculoskeletal Questionnaire.
Results: A total of 249 participants were included in this cross-sectional study. The body parts that were reported with highest prevalence of musculoskeletal pain were the upper back (70.3%), neck (65.9%), and wrists/hands (68.7%). The SAS scores were correlated with duration of smartphone use on a typical day (P = 0.001), duration of owning a smartphone (P = 0.027), and musculoskeletal pain prevalence in the neck (P = 0.001), wrists/hands (P = 0.001), shoulders (P = 0.025), and upper back (P = 0.023). The SAS score was significantly associated with prevalence of musculoskeletal pain in the neck (odd ratio [OR], 1.08; 95% confidence interval [CI], 0.98-1.10; P = 0.002), wrists/hands (OR, 1.07; 95% CI, 0.97-1.09; P = 0.001), and upper back (OR, 1.10; 95% CI, 0.98-1.11; P = 0.033).
Conclusions: The findings indicated that the upper back, neck, and wrists/hands have a higher prevalence of musculoskeletal pain among smartphone users, particularly those with a smartphone addiction. Smartphone addiction scores were correlated with duration of smartphone use on a typical day, duration of owning smartphone, and musculoskeletal pain prevalence in the neck, wrists/hands, shoulders, and upper back.

Background: Trigeminal neuralgia is a debilitating craniofacial pain syndrome that is characterized by paroxysms of intense, short-lived electric shock-like pains in the trigeminal nerve distribution. Recently, the presence of triggers has become one of the key diagnostic criteria in the 3rd edition of the International Classification of Headache Disorders. Light touch is the most common trigger, however other non-mechanical triggers, such as cold weather and certain foods, have been thought to provoke trigeminal neuralgia anecdotally. We aimed to characterize the prevalence and characteristics of these atypical triggers.
Methods: We conducted a retrospective, cross-sectional study of atypical triggers in trigeminal neuralgia patients seen in a tertiary pain clinic in Singapore. Patients were recruited via clinic records, and study data were identified from physician documentation.
Results: A total of 60 patients met the inclusion criteria. Weather triggers were observed in 12 patients (20%), of which five patients (8%) reported strong winds, 4 patients (7%) reported cold temperatures, and 3 patients (5%) reported cold winds as triggers. Fifteen patients (25%) had a specific food trigger, of which 10 patients (17%) reported hard or tough food, 5 patients (8%) reported hot/cold food, 4 patients (7%) reported spicy food, and 2 patients (3%) reported sweet food as triggers.
Conclusions: Although trigeminal neuralgia is most commonly triggered by mechanical stimuli, atypical triggers such as cold temperatures and certain foods are seen in a significant proportion of patients. These atypical triggers may share a common pathway of sensory afferent Aδ fiber activation.

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism.
Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed.
Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine.
Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

Background: This study used bibliometric analysis of articles published about the topic of regional anesthesia from 1980-2019 with the aim of determining which countries, organizations, and authors were effective, engaged in international cooperation, and had the most cited articles and journals.
Methods: All articles published from 1980-2019 included in the Web of Science database and found using the keywords regional anesthesia/anaesthesia, spinal anesthesia/anaesthesia, epidural anesthesia/anaesthesia, neuraxial anesthesia/ anaesthesia, combined spinal-epidural, and peripheral nerve block in the title section had bibliometric analysis performed. Correlations between the number of publications from a country with gross domestic product (GDP), gross domestic product (at purchasing power parity) per capita (GDP PPP), and human development index (HDI) values were investigated with the Spearman correlation coefficient. The number of articles that will be published in the future was estimated with linear regression analysis.
Results: Literature screening found 11,156 publications. Of these publications, 6,452 were articles. The top 4 countries producing articles were United States of America (n = 1,583), Germany (585), United Kingdom (510), and Turkey (386). There was a significant positive correlation found between the GDP, GDP PPP, and HDI markers for global countries with publication productivity (r = 0.644, P < 0.001; r = 0.623, P < 0.001, r = 0.542, P < 0.001). The most productive organizations were Harvard University and the University of Toronto.
Conclusions: This comprehensive study presenting a holistic summary and evaluation of 6,452 articles about this topic may direct anesthesiologists, doctors, academics, and students interested in this topic.

Background: Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms.
Methods: An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of proand anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay.
Results: Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)- 1β, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn.
Conclusions: The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomecha-nisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2) signaling in cisplatininduced neuropathic pain.
Methods: CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting.
Results: The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001).
Conclusions: The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.

Background: Prolotherapy is a proliferation therapy as an alternative medicine. A combination of dextrose solution and lidocaine is usually used in prolotherapy. The concentrations of dextrose and lidocaine used in the clinical field are very high (dextrose 10%-25%, lidocaine 0.075%-1%). Several studies show about 1% dextrose and more than 0.2% lidocaine induced cell death in various cell types. We investigated the effects of low concentrations of dextrose and lidocaine in fibroblasts and suggest the optimal range of concentrations of dextrose and lidocaine in prolotherapy.
Methods: Various concentrations of dextrose and lidocaine were treated in NIH- 3T3. Viability was examined with trypan blue exclusion assay and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Migration assay was performed for measuring the motile activity. Extracellular signal-regulated kinase (Erk) activation and protein expression of collagen I and α-smooth muscle actin (α-SMA) were determined with western blot analysis.
Results: The cell viability was decreased in concentrations of more than 5% dextrose and 0.1% lidocaine. However, in the concentrations 1% dextrose (D1) and 0.01% lidocaine (L0.01), fibroblasts proliferated mildly. The ability of migration in fibroblast was increased in the D1, L0.01, and D1 + L0.01 groups sequentially. D1 and L0.01 increased Erk activation and the expression of collagen I and α-SMA and D1 + L0.01 further increased. The inhibition of Erk activation suppressed fibroblast proliferation and the synthesis of collagen I.
Conclusions: D1, L0.01, and the combination of D1 and L0.01 induced fibroblast proliferation and increased collagen I synthesis via Erk activation.

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige®) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.

Background: The present investigation explored the therapeutic actions of oleuropein along with the possible signaling pathway involved in attenuating neuropathic pain in chronic constriction injury (CCI) and vincristine-induced neuropathic pain in male rats.
Methods: Four loose ligatures were placed around the sciatic nerve to induce CCI, and vincristine (50 μg/kg) was injected for 10 days to develop neuropathic pain. The development of cold allodynia, mechanical allodynia, and mechanical hyperalgesia was assessed using different pain-related behavioral tests. The levels of H2S, cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), orexin, and nuclear factor erythroid-2-related factor 2 (Nrf2) were measured in the sciatic nerve.
Results: Treatment with oleuropein for 14 days led to significant amelioration of behavioral manifestations of neuropathic pain in two pain models. Moreover, oleuropein restored both CCI and vincristine-induced decreases in H2S, CSE, CBS, orexin, and Nrf2 levels. Co-administration of suvorexant, an orexin receptor antagonist, significantly counteracted the pain-attenuating actions of oleuropein and Nrf2 levels without modulating H2S, CSE and CBS.
Conclusions: Oleuropein has therapeutic potential to attenuate the pain manifestations in CCI and vincristine-induced neuropathic pain, possibly by restoring the CSE, CBS, and H2S, which may subsequently increase the expression of orexin and Nrf2 to ameliorate behavioral manifestations of pain.