Comparison of Impressions of COVID-19 Vaccinations Stratified by the Number of Vaccinations Among Japanese Healthcare Professional University Students.

OBJECTIVE: Coronavirus infectious disease, that emerged in 2019 (COVID-19) has been a major public health issue not only in Japan, but also worldwide, and the implementation of a proper vaccination strategy has been important. To promote vaccination, the present study compared impressions of COVID-19 vaccinations stratified by the number of vaccinations among healthcare professional university students in Okayama, Japan, and suggests better vaccination strategies. METHOD: A total of 212 Japanese healthcare professional university students were enrolled in this clinical qualitative study using the text mining method. A self-reported questionnaire, including questions such as "What do you think about COVID-19 vaccinations?" was performed. We also examined the number of vaccinations, sex, history of COVID-19 infection, and daily mask use. RESULTS: A total of 5,935 words were obtained and "Think" (169 times) was the most frequently used followed by "Inject" (108 times), "Inoculation" (97 times), "Vaccine" (83 times), "Corona" (66 times) and "Side effects" (49 times). Characteristic words were "Safety" in non-vaccinated subjects and "Side effects" and "Necessary" in vaccinated subjects. In addition, "Safety" in non-vaccinated men and "Frightening" in non-vaccinated women were characteristic and fundamental features. CONCLUSION: Impressions of COVID-19 vaccinations stratified by the number of vaccinations differed among healthcare professional university students. The provision of appropriate information on safety to non-vaccinated subjects and side effects to vaccinated subjects appears to be necessary. In addition, sex-specific information may be required for non-vaccinated subjects.

Calcium-binding protein 7 expressed in muscle negatively regulates age-related degeneration of neuromuscular junctions in mice.

The neuromuscular junction (NMJ) forms centrally in myotubes and, as the only synapse between motor neuron and myotube, are indispensable for motor activity. The midmuscle formation of NMJs, including midmuscle-restricted expression of NMJ-related genes, is governed by the muscle-specific kinase (MuSK). However, mechanisms underlying MuSK-mediated signaling are unclear. Here, we find that the Calcium-binding protein 7 (Cabp7) gene shows midmuscle-restricted expression, and muscle-specific depletion of Cabp7 in mice accelerated age-related NMJ degeneration, muscle weakness/atrophy, and motor dysfunction. Surprisingly, forced expression in muscle of CIP, an inhibitory peptide of the negative regulator of NMJ formation cyclin-dependent kinase 5 (Cdk5), restored NMJ integrity and muscle strength, and healed muscle atrophy in muscle-specific Cabp7-deficient mice, which showed increased muscle expression of the Cdk5 activator p25. These findings together demonstrate that MuSK-mediated signaling induces muscle expression of Cabp7, which suppresses age-related NMJ degeneration likely by attenuating p25 expression, providing insights into prophylactic/therapeutic intervention against age-related motor dysfunction.

Assessment of Office-Based Probing with Dacryoendoscopy for Treatment of Congenital Nasolacrimal Duct Obstruction: A Retrospective Study.

We aimed to evaluate the safety and efficacy of office-based probing with dacryoendoscopy under local anesthesia for congenital nasolacrimal duct obstruction (CNLDO). This single-institution study retrospectively reviewed data on 72 eyes of 64 consecutive children (38 boys, 43 eyes; 26 girls, 29 eyes), aged between 6 and 17 (mean age: 10.0 ± 2.7) months with suspected CNLDO, from July 2016 to February 2022. These patients underwent probing with dacryoendoscopy under local anesthesia. CNLDO was diagnosed clinically based on the presence of epiphora and sticky eyes due to mucous discharge commencing within the first 3 months of life, increased tear meniscus height, and fluorescein dye disappearance test results. A total of 63 of the 72 eyes had narrowly defined CNLDO, and 9 eyes had other types of obstructions. The intervention success rate was 100% (63/63 eyes) for patients with typical CNLDO and 97.2% (70/72 eyes) for the entire study cohort. Moreover, CNLDO was classified into five types based on the features of the distal end of the nasolacrimal duct. Probing with dacryoendoscopy is safe and yields a high success rate in pediatric patients with CNLDO. This is the first study to assess the safety and efficacy of probing with dacryoendoscopy under local anesthesia in pediatric patients with CNLDO.

Marked Choroidal Thinning Observed after Intravitreal Brolucizumab Injection.

Introduction: Here, we report a case of severe intraocular inflammation (IOI) and prominent choroidal thinning following the initial intravitreal brolucizumab injection (IVBr). Case Presentation: The patient was a 75-year-old Japanese man with type 2 age-related macular degeneration of both eyes. Until 2015, he had undergone two intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and two photodynamic therapies in his right eye. His decimal best-corrected visual acuity (BCVA) was 0.1 in the right eye and 0.1 in the left eye. Central choroidal thickness (CCT) measured 240 µm in his right eye. IVBr was administered to the right eye. The patient reported pain in the right eye 23 days after the injection. On day 26, panuveitis and retinal vasculitis were observed in the right eye. CCT measured 436 µm. On the same day, a sub-tenon triamcinolone injection was administered. On day 42, retinal inflammation remained at a similar level. The CCT decreased to 164 µm. On day 68, the intraocular pressure (IOP) in the right eye increased to 39 mm Hg, and IOI persisted. On day 89, the patient's eye pain disappeared, and the IOP decreased to 13 mm Hg. On day 225, the IOI and symptoms were completely resolved. The decimal BCVA was 0.04 in the right eye, and CCT measured 84 µm. Conclusion: Brolucizumab is a highly effective anti-VEGF drug; however, it has the potential to induce inflammation in tissues adjacent to the retina and may occasionally cause irreversible sequelae.

Efficacy of Coagulofibrinolytic Markers for Postoperative Prediction of Venous Thromboembolism in Colorectal Surgery Patients: A Retrospective Observational Study.

Objectives: A low rate of the incidence of venous thromboembolism (VTE) after surgeries that are preoperatively classified as having high risk of VTE has been reported in recent years. We seek to identify the optimal cases to receive perioperative pharmacologic thromboprophylaxis. In this study, we evaluated the incidence rate of VTE among patients undergoing colorectal surgery who did not receive perioperative pharmacologic thromboprophylaxis, and the ability of coagulofibrinolytic markers to predict the postoperative development of VTE. Methods: We retrospectively analyzed the rate of postoperative development of VTE in 70 patients undergoing elective colorectal surgery without perioperative pharmacologic thromboprophylaxis and the ability of coagulofibrinolytic markers to predict the development of VTE. Results: The incidence of VTE was observed in 11 patients (15.7%); all cases were asymptomatic and distal-type deep vein thrombosis (DVT). Comparisons of time course changes in perioperative coagulofibrinolytic markers between patients with and without DVT revealed significant differences in soluble fibrin (SF), thrombin-antithrombin complex (TAT), fibrin/fibrinogen degradation product (FDP) and D-dimer. Dynamic postoperative physiological coagulofibrinolytic responses were shown, but all four markers at each postoperative point demonstrated moderate accuracy (median area under the curve [AUC]: 0.788, median sensitivity: 0.865, median specificity: 0.644) for predicting the development of DVT. Conclusions: The incidence of postoperative VTE was low in patients with colorectal surgery even in those who did not receive perioperative pharmacologic thromboprophylaxis. SF, TAT, FDP and D-dimer were useful for predicting the development of DVT when we set cut-off values taking the physiological perioperative coagulofibrinolytic responses into consideration.

Visual Prognostic Factors in Eyes with Subretinal Fluid Associated with Branch Retinal Vein Occlusion.

We investigated whether foveal ellipsoid zone (EZ) status affects visual prognosis in eyes with subretinal fluid (SRF) associated with branch retinal vein occlusion (BRVO). We included 38 eyes retrospectively and classified those with or without a continuous EZ on the SRF of the central foveola on the vertical optical coherence tomography (OCT) image at the initial visit as intact (n = 26) and disruptive EZ (n = 12) groups, respectively. In addition, we classified the intact EZ eyes into clear (n = 15) and blurred (n = 11) EZ groups according to whether EZ on the SRF was observed distinctly or not. Multiple regression analyses showed that baseline EZ status significantly correlated (p = 0.0028) with the 12-months logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), indicating that baseline intact EZ significantly improves visual prognosis. The 12-months logMAR BCVA of the intact EZ group was significantly better (p < 0.001) than that of the disruptive EZ group, and did not differ significantly between the clear and blurred EZ groups. Thus, baseline foveal EZ status on vertical OCT images can be a novel biomarker for visual prognosis in eyes with SRF associated with BRVO.

Three-Year Outcomes of Immediate Primary Phacoemulsification on Acute Primary Angle Closure Eyes and the Fellow Eyes.

Purpose: This study investigated the long-term outcomes (> 3 years) of immediate primary phacoemulsification in eyes with acute primary angle closure (APAC) and in the fellow eyes with shallow anterior chamber to prevent APAC development. Patients and Methods: This is a retrospective study of phacoemulsification for APAC using bilateral eyes. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), and number of IOP-lowering medications at the preoperative examination (Pre), postoperative month 1 (1m), year 3 (3y), and last visit were compared between 14 eyes with APAC and their 14 fellow eyes. The number of corneal endothelial cells (CECs) at Pre and at more than 2 weeks after phacoemulsification was compared. The visual field mean deviation (MD) within 1 year after phacoemulsification and at the last visit was also compared. Results: For APAC eyes, BCVA was significantly improved at 1m, 3y, and at the last visit as compared with Pre (p < 0.05). IOP significantly decreased at 1m, 3y, and at the last visit compared with Pre (p < 0.05). IOP-lowering medication use decreased significantly from Pre to 1m (p < 0.05). The number of CECs was not significantly different between Pre and more than 2 weeks after phacoemulsification. BCVA was significantly worse in APAC eyes than in fellow eyes at Pre (p < 0.05). IOP and the number of IOP-lowering medications were significantly higher in APAC eyes than in fellow eyes at Pre (p < 0.05). Conclusion: Primary phacoemulsification improved visual acuity for APAC eyes and maintained good IOP control without the need for reoperation. Moreover, it preserved the number of CECs for the APAC and fellow eyes in the long term.

Imaging Classification of Constipation.

Objectives: The diagnosis of patients with chronic constipation is very complicated. This study aimed to develop a simple imaging classification for the diagnosis of chronic constipation by abdominal computed tomography (CT). Methods: Sixty-two patients who underwent abdominal CT in our hospital between January and June 2022 were enrolled. The CT values of the stool in the rectum and cecum were measured in patients with chronic constipation (C group) and in those without (non-C group). Results: A strong correlation was observed between the Bristol Stool Form Scale (BSFS) and the CT value of rectal stool. Furthermore, the rectal stool CT value was significantly higher in patients with chronic constipation than in those without. The CT value of cecal stool did not differ between the two groups. The cecal stool CT value was significantly higher in patients with severe constipation (BSFS 1) than in those with BSFS 2-6. A cutoff CT value of 100 was selected as the optimal value for indicating chronic constipation. Conclusions: Abdominal CT was useful in the diagnosis of chronic constipation. If the patient had constipation, the optimal cutoff CT value was 100.

Cadaveric and CT angiography study of vessels around the transverse colon mesentery.

BACKGROUND: Laparoscopic and robotic surgery for transverse colon cancer are difficult due to complex fusion of the foregut and midgut and variation of the vessels of the transverse colon. Although the vessels of the right colon have been investigated, middle colic artery (MCA) variation and the relationship with vessels around the transvers colon are unknown. We investigated variation of the MCA using computed tomography angiography (CTA) and cadaver specimen and the relationship between the superior mesenteric vein (SMV) and MCA using CTA. The classification of vessels around the transverse colon may lead to safer and reliable surgery. METHODS: This study included 505 consecutive patients who underwent CTA in our institution from 2014 to 2020 and 44 cadaver specimens. Vascular anatomical classifications and relationships were analyzed using CT images. RESULTS: The MCA was defined as the arteries arising from the superior mesenteric artery (SMA) that flowed into the transverse colon at the distal ends. The classifications were as follows: type I, branching right and left from common trunk; type II, the right and left branches bifurcated separately from the SMA; and type III, the MCA branched from a vessel other than the SMA. Type II was subclassified into two subtypes, type IIa with one left branch and type IIb with two or more left branches from SMA. In the CTA and cadaver studies, respectively, the classifications were as follows: type I, n = 290 and n = 31; type IIa, n = 211 and n = 13; type IIb, n = 3 and n = 0; and type III, n = 1 and n = 0. We classified the relationship between the MCA and left side of the SMV into three types: type A, a common trunk runs along the left edge of the SMV (n = 173; 59.7%); type B, a right branch of the MCA runs along the left edge of the SMV (n = 116; 40.0%); and type C, the MCA runs dorsal of the SMV (n = 1; 0.3%). CONCLUSIONS: This study revealed that The MCA branching classifications and relationship between the SMV and MCA. Preoperative CT angiography may be able to reliably identify vessel variation, which may be useful in clinical practice.

Tangentially migrating cells differentiate into stratum griseum central neurons to form tectofugal visual pathway in the developing chick optic tectum.

BACKGROUND: The optic tectum is the main visual processor of nonmammalian vertebrates and relays visual information from the eye to the telencephalon via the tectofugal pathway. In the development of the avian optic tectum, while the multipolar neurons are arranged by tangential migration, the behavior of individual cells in tangential migration, neural differentiation, and cell fate remain unclear. Here, we pursued the transition of tangentially migrating cells and their involvement in visual circuit formation during chick development. RESULTS: After tangential movement along the axons, the migrating cells relocated to the upper layers and turned back upon differentiation toward the multipolar neurons. The multipolar neurons are destined to differentiate into the stratum griseum central (SGC) neurons with the large dendritic field, which form the tectorotundal projection. Trans-synaptic virus labeling demonstrated that the tangentially migrating cells eventually participate in the tectofugal visual pathway. CONCLUSIONS: These results indicate that tangential migration is a crucial process in the formation of the tectofugal visual pathway during the development of the optic tectum.

Impact of the hospital volume and setting on postoperative complications of surgery for gastroenterological cancers in a regional area of Western Japan.

PURPOSE: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan. METHODS: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery. RESULTS: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes. CONCLUSION: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed.

Clinical evaluation of cell-direct polymerase chain reaction-based nucleic acid lateral flow immunoassay for rapid detection of bacterial pathogens in clinically suspected sepsis: A multi-center study in Japan.

Blood culture, a method for identifying causative agents of bacterial sepsis, requires several days. The combination of cell-direct polymerase chain reaction and nucleic acid lateral flow immunoassay (cdPCR-NALFIA) is a simple and sensitive detection method for identifying pathogenic bacteria. Furthermore, this assay, when applied directly to blood samples yields results within 4.5 h, without requiring culture. This study was performed at five hospitals in Japan between 2013 and 2016. Blood samples from 73 patients with clinically suspected sepsis yielded 18 positive blood cultures, and the isolated bacterial species were detectable using cdPCR-NALFIA in nine samples. Thirteen samples were positive on cdPCR-NALFIA. In total, 17 samples confirmed to have bacterial species were detectable using cdPCR-NALFIA and/or blood culture with a true positive rate of 76.5% and 64.7%, respectively. The combination of blood culture and cdPCR-NALFIA could improve the rate of detection of bacterial sepsis.

Sinobronchial Syndrome Patients with Suspected Non-Tuberculous Mycobacterium Infection Exacerbated by Exophiala dermatitidis Infection.

Background: Exophiala dermatitidis is an environmental black fungus that rarely causes respiratory infections, yet its pathophysiological features and treatment regimens have not been established. Case Series: Two cases of exacerbations of chronic bronchitis and sinusitis due to E. dermatitidis infection in Japan are presented. Both patients were women, and non-tuberculous Mycobacterium (NTM) infection was suspected based on chest radiological findings, but E. dermatitidis was detected from bronchial lavage fluid and nasal mucus, respectively. Both cases were successfully treated by antifungal agents such as liposomal amphotericin B, voriconazole, and itraconazole, but clarithromycin, rifampicin, ethambutol, and sitafloxacin for NTM were not effective. Conclusion: E. dermatitidis can become a respiratory pathogen, especially in patients with chronic sinobronchial syndrome.

Pulmonary and Disseminated Mycobacterium avium Complex Cases Confirmed by Tissue-Direct Polymerase Chain Reaction-Based Nucleic Acid Lateral Flow Immunoassay of Formalin-Fixed Paraffin-Embedded Tissues.

Background: Detection of Mycobacterium avium complex (MAC) in tissue is essential for the diagnosis of MAC infections when the Mycobacterium is not isolated from sputum. However, detection of MAC in paraffin-embedded sections has not been established. Methods: We encountered two patients with suspected MAC infections after surgery: patient 1 had a pulmonary nodule that was initially suspected to be lung cancer and was excised under video-assisted thoracoscopic surgery (VATS). Patient 2, who was under treatment with steroids and anti-IL-6 inhibitors for rheumatoid arthritis, was suspected to have disseminated ileocecal cancer with metastasis to the lung and skin. In both cases, we postoperatively detected MAC genes in paraffin-embedded tissue sections using the novel mycobacterial nucleic acid identification test, ie tissue-direct polymerase chain reaction (tdPCR)-based nucleic acid lateral flow immunoassay (NALFIA). Both patients showed granulomatous lesions with hematoxylin-eosin staining, and mycobacteria by Ziehl-Neelsen staining in tissue sections from the lung and skin, respectively, although MAC were not isolated from the sections. MAC genes were finally detected by tdPCR-NALFIA in both cases. Conclusion: Although Ziehl-Neelsen staining and culture tests are the gold standard in identifying causative mycobacteria, the rapid results of tdPCR-NALFIA performed simultaneously with sputum and/or tissue culture may make it an important auxiliary diagnostic tool for identifying mycobacterial infection, leading to improvement in the management of MAC patients.

Long-term prognosis of laparoscopic gastrectomy for patients on antithrombotic therapy: a retrospective cohort study.

PURPOSE: Few studies have reported on the interactions between gastrectomy and antithrombotic therapy, especially the long-term prognosis. We aimed to clarify the short- and long-term prognosis of gastrectomy for patients on antithrombotic therapy. METHODS: We reviewed the perioperative data and survival rate of patients who underwent laparoscopic distal gastrectomy (LDG) at our institute between 2010 and 2013. RESULTS: There were 119 patients enrolled in this retrospective study: 31 who were taking antithrombotic drugs (antithrombotic therapy (ATT) group), and 88 who were not (non-ATT group). The mean age was significantly higher in the ATT group than in the non-ATT group. No significant differences were observed in the amount of intraoperative bleeding or blood hemoglobin level after surgery between the groups. Bleeding complications occurred in only one patient from the ATT group, and the postoperative complication rate was comparable between the groups. During follow-up, cerebrovascular or cardiovascular events developed in 19.4% of the ATT group patients and 4.5% of the non-ATT group patients; however, there were no significant differences in the 5-year overall survival rates between the groups (ATT group, 76.9%; non-ATT group, 82.9%). CONCLUSIONS: Antithrombotic therapy did not affect the short-term or long-term prognosis of patients after LDG.

A case of successful laparoscopic intraperitoneal onlay mesh plus technique repair for perineal hernia after laparoscopic abdominoperineal resection.

The frequency of secondary perineal hernia after abdominoperineal resection has been reported as 0.83%-26%. The optimal surgery for secondary perineal hernia and surgical indication remains controversial. An 87-year-old woman diagnosed with lower rectal cancer underwent laparoscopic abdominoperineal resection. Follow-up computed tomography at 6 months postoperatively revealed secondary perineal hernia. She reported no discomfort and no incarceration was apparent, but she complained of perineal discomfort 3 months later. Laparoscopic repair surgery was performed using an intraperitoneal onlay mesh plus technique with VENTRALIGHT® ST mesh (Medicon, Osaka, Japan), a non-absorbable mesh with a biodegradable coating. No recurrence of peritoneal hernia was seen as of 3 months postoperatively. A time lag can exist between imaging findings and symptom appearance. This laparoscopic intraperitoneal onlay mesh plus technique might become the optimal treatment for perineal hernia.

Tumor Screening, Incidence, and Treatment for Patients with Severe Motor and Intellectual Disabilities.

BACKGROUND: The increasing age of patients with severe motor and intellectual disabilities (SMID) has become a serious concern. Few studies have investigated tumor treatment in this population. METHODS: Tumor treatments for 12 SMID patients were examined. RESULTS: Blood tests and ultrasonography were useful for screening. With regard to treatment, surgery for SMID patients was performed in the same manner as for patients without SMID, and the results were generally satisfactory, without major complications. Typically, cancer was diagnosed at an advanced stage, and many metachronous double cancers were observed. CONCLUSIONS: Treatment yielded satisfactory results for patients with SMID and their families. Future studies should examine the clinical significance of screening and tumor operative method for patients with SMID.

Perioperative coagulofibrinolytic responses in colorectal surgery patients without chemical thromboprophylaxis: a retrospective observational study.

PURPOSE: During the perioperative period, coagulofibrinolytic activation occurs, which occasionally results in thromboembolic complications. However, natural perioperative coagulofibrinolytic responses have not been well investigated. The present study examined perioperative coagulofibrinolytic changes and their association with the development of venous thromboembolism (VTE). METHODS: We retrospectively analyzed the changes in coagulofibrinolytic markers for 7 days in 70 patients undergoing elective colorectal surgery. To explore the natural coagulofibrinolytic response, we investigated patients not undergoing perioperative chemical thromboprophylaxis. RESULTS: Coagulation activation occurred from just after surgery to postoperative day (POD) 1, followed by a gradual decrease, but persisted to even POD 7. Fibrinolytic activity showed a tri-phasic response: activation, shutdown and reactivation. Consequently, fibrin/fibrinogen degradation product (FDP) and D-dimer levels continued to increase until POD 7. The development of deep vein thrombosis (DVT) was observed in 11 patients (15.7%). Postoperative sustained hyper-coagulation [soluble fibrin (SF) or thrombin-antithrombin complex (TAT) values on POD 7 > their normal limits] was significantly associated with the development of DVT (SF, p < 0.001; TAT, p = 0.001). CONCLUSION: We found initial coagulation activation and a tri-phasic response of fibrinolytic activity after colorectal surgery. Thus, physicians need to pay attention to these responses when attempting to prevent or treat VTE.

The arrival time of indocyanine green in tissues can be a quantitative index because of its correlation with tissue oxygen saturation: A clinical pilot study.

Indocyanine green (ICG) fluorescence angiography has recently been reported useful as a method for predicting intestinal blood flow and may reduce anastomotic leakage. However, the quantification method for ICG fluorescence angiography has not been established. We usually measure the tissue oxygen saturation (StO2 ) in the intestinal tract via near-infrared spectroscopy, as it is able to measure the oxygen concentration accurately and immediately shows objective data. In this study, we propose that the time to reach the anastomotic site after intravenous ICG injection is an effective parameter for quantifying ICG fluorescence angiography from the comparison to the data of StO2 in the intestinal tract.

Endothelin receptor type A is involved in the development of oxaliplatin-induced mechanical allodynia and cold allodynia acting through spinal and peripheral mechanisms in rats.

Oxaliplatin, a platinum-based chemotherapeutic agent, frequently causes severe neuropathic pain typically encompassing cold allodynia and long-lasting mechanical allodynia. Endothelin has been shown to modulate nociceptive transmission in a variety of pain disorders. However, the action of endothelin varies greatly depending on many variables, including pain causes, receptor types (endothelin type A (ETA) and B (ETB) receptors) and organs (periphery and spinal cord). Therefore, in this study, we investigated the role of endothelin in a Sprague-Dawley rat model of oxaliplatin-induced neuropathic pain. Intraperitoneal administration of bosentan, a dual ETA/ETB receptor antagonist, effectively blocked the development or prevented the onset of both cold allodynia and mechanical allodynia. The preventive effects were exclusively mediated by ETA receptor antagonism. Intrathecal administration of an ETA receptor antagonist prevented development of long-lasting mechanical allodynia but not cold allodynia. In marked contrast, an intraplantar ETA receptor antagonist had a suppressive effect on cold allodynia but only had a partial and transient effect on mechanical allodynia. In conclusion, ETA receptor antagonism effectively prevented long-lasting mechanical allodynia through spinal and peripheral actions, while cold allodynia was prevented through peripheral actions.