48 results on '"Kusuda, R."'
Search Results
2. Antigenicity and N-terminal amino acid sequence of a 35 kDa porin-like protein of Listonella (Vibrio) anguillarum: comparison among different serotypes and other bacterial species
- Author
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Suzuki, S., Kuroe, K., Yasue, K., and Kusuda, R.
- Published
- 1996
3. (153) The interleukin 27 (IL-27) protects mice from neuropathic pain development through up-regulation of anti-inflammatory cytokine IL-10
- Author
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Fonseca, M. Mendes, primary, Santa-Cecilia, F., additional, Kusuda, R., additional, Ferreira, D., additional, Bezerra, F., additional, Ferreira, M., additional, Guimarães, R., additional, Cunha, F., additional, and Cunha, T., additional
- Published
- 2017
- Full Text
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4. Biexciton state causes photoluminescence fluctuations in CdSe/ZnS core/shell quantum dots at high photoexcitation densities
- Author
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Yoshikawa, N., primary, Hirori, H., additional, Watanabe, H., additional, Aoki, T., additional, Ihara, T., additional, Kusuda, R., additional, Wolpert, C., additional, Fujiwara, T. K., additional, Kusumi, A., additional, Kanemitsu, Y., additional, and Tanaka, K., additional
- Published
- 2013
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5. Plasma corticosterone levels in mouse models of pain
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Benedetti, M., primary, Merino, R., additional, Kusuda, R., additional, Ravanelli, M.I., additional, Cadetti, F., additional, dos Santos, P., additional, Zanon, S., additional, and Lucas, G., additional
- Published
- 2011
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6. 358 UP‐REGULATION OF MICRORNA‐16 IN THE DORSAL ROOT GANGLION AND SPINAL CORD DORSAL HORN FOLLOWING PERIPHERAL NERVE INJURY
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Kusuda, R., primary, Zanon, S., additional, Souza, T. Amaral E., additional, Cadetti, F., additional, Zanon‐Baptista, N., additional, De Lucca, F.L., additional, and Lucas, G., additional
- Published
- 2007
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7. Characterization of the intestinal macrophage in Japanese flounder
- Author
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Kintsuji, H., primary, Kawahara, E., additional, Kondo, M., additional, Tomonaga, S., additional, Mizukami, M., additional, and Kusuda, R., additional
- Published
- 1997
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8. Polymerase chain reaction (PCR) amplification of bacilliform virus (RV‐PJ) DNA in Penaeus japonicus Bate and systemic ectodermal and mesodermal baculovirus (SEMBV) DNA in Penaeus monodon Fabricius
- Author
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Takahashi, Y, primary, Itami, T, additional, Maeda, M, additional, Suzuki, N, additional, Kasornchandra, J, additional, Supamattaya, K, additional, Khongpradit, R, additional, Boonyaratpalin, S, additional, Kondo, M, additional, Kawai, K, additional, Kusuda, R, additional, Hirono, I, additional, and Aoki, T, additional
- Published
- 1996
- Full Text
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9. Genogrouping of birnaviruses isolated from marine fish: a comparison of VP2/NS junction regions on genome segment A
- Author
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Hosono, N, primary, Suzuki, S, additional, and Kusuda, R, additional
- Published
- 1996
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10. Comparative pathogenicity study on antigenically variant strains of Enterococcus seriolicida
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Alim, S R, primary, Kawai, K, additional, and Kusuda, R, additional
- Published
- 1996
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- View/download PDF
11. Evidence for relatedness of Japanese isolates of birnaviruses from marine fish to IPNV
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HOSONO, N., primary, SUZUKI, S., additional, and KUSUDA, R., additional
- Published
- 1994
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12. The effect of triploidy on phagocytosis, leucocyte migration, antibody and complement levels of ayu, Plecoglossus altivelis
- Author
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KUSUDA, R, primary, SALATI, F, additional, HAMAGUCHI, M, additional, and KAWAI, K, additional
- Published
- 1991
- Full Text
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13. Oral vaccination of glass eel of Anguilla japonica against Edwardsiella tarda infection
- Author
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SALATI, F, primary, ONO, K, additional, and KUSUDA, R, additional
- Published
- 1991
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14. Enterococcus seriolicida sp. nov., a Fish Pathogen
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Kusuda, R., primary, Kawai, K., additional, Salati, F., additional, Banner, C. R., additional, and Fryer, J. L., additional
- Published
- 1991
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15. Pasteurella piscicida infection in Yatabe blenny, Pictiblennius yatabei.
- Author
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Hamaguchi, M., primary, Usuki, H., additional, and Kusuda, R., additional
- Published
- 1991
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16. Studies on the pathogenesis of streptococcal infection in cultured yellowtails, <em>Seriola</em> spp.: effect of crude exotoxin fractions from cell-free culture on experimental streptococcal infection.
- Author
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Kimura, H. and Kusuda, R.
- Subjects
- *
STREPTOCOCCAL diseases , *BACTERIAL diseases , *INFECTION , *BACTERIA , *SERIOLA , *PATHOGENIC bacteria - Abstract
Exotoxins prepared from streptococcal bacteria of Serbia spp. origin were grown in fluid culture and fractionates of the supernatant used in toxicity studies in Seriola by oral and percutaneous exposure. Toxic fractions were then applied simultaneously with oral challenge with Streptococcus spp. bacteria. Two fractions E and G were shown to have a significant effect on the pathogenesis of infection. [ABSTRACT FROM AUTHOR]
- Published
- 1982
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17. Studies on the pathogenesis of streptococcal infection in cultured yellowtails <em>Seriola</em> spp.: effect of the cell free culture on experimental streptococcal infection.
- Author
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Kimura, H. and Kusuda, R.
- Subjects
- *
BACTERIAL diseases , *STREPTOCOCCAL diseases , *BLOOD , *FISHES , *MICROBIAL virulence , *INFECTION - Abstract
A previous paper has revealed that experimental streptococcal infection was associated with a rapid growth of the intestinal bacteria, suggesting association of the condition with an exotoxin. The present study was undertaken to see the effect of the exotoxin on the streptococcal infection by administering cell free culture before the bacterial challenge, Cell free culture of Streptococcus sp. strain YT-3 was inoculated intramuscularly at a dosage of 0.5 ml per 100 g body weight 1 h prior to bacterial challenge. Three fish were killed at intervals after challenge for viable counting of bacteria in the viscera and blood. Intramuscular inoculation with either low virulent or virulent bacteria alone at dosages of 106 to 107 cells did not produce the disease in the fish, with almost complete clearance of the bacteria from the viscera and blood within 120 h. When the exotoxin was inoculated intramuscularly prior to the bacterial challenge, however, either low virulent or virulent bacteria at 106 to 107 cells could produce fatal infection with prominent streptococcal clinical signs. [ABSTRACT FROM AUTHOR]
- Published
- 1979
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18. Polymerase chain reaction (PCR) amplification of bacilliform virus (RV-PJ) DNA in <em>Penaeus japonicus</em> Bate and systemic ectodermal and mesodermal baculovirus (SEMBV) DNA in <em>Penaeus monodon</em> Fabricius.
- Author
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Takahashi, Y., Itami, I., Maecia, M., Suzuki, N., Kasornchandra, J., Supamattaya, K., Khongpradw, R., Boonyaratpafln, S., Kondo, M., Kawai, K., Kusuda, R., Hirono, I., and Aoki, T.
- Subjects
POLYMERASE chain reaction ,FISH diseases ,ELECTRON microscopes ,VIRUSES ,DNA polymerases ,SHRIMPS ,INFECTION - Abstract
This article presents information on polymerase chain reaction amplification of bacilliform virus DNA. Diseased shrimp showed white spots on the inside surface of the carapace and reddish discolouration of the body. A non-occluded bacilliform virus was observed under the transmission electron microscope (TEM) and was demonstrated to be highly pathogenic to kuruma shrimp by infection trials. Epidemiological surveys indicated that this disease was originally found in an imported population of juvenile kuruma shrimp from China. Both of these infections have similar clinical signs caused by a non-occluded bacilliform virus and have been causing serious economic losses in Asian shrimp culture.
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- 1996
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19. Comparative pathogenicity study on antigenically variant strains of <em>Enterococcus seriolicida</em>.
- Author
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Alim, S. R., Kawai, K., and Kusuda, R.
- Subjects
ENTEROCOCCUS ,STREPTOCOCCACEAE ,SERUM ,BLOOD plasma ,AGGLUTINATION tests ,ANTIGEN-antibody reactions - Abstract
Enterococcus seriolicida strains were divided into two groups, agglutinating and nonagglutinating, by a slide agglutination test using antiserum against the YT-3 strain. Intraperitoneal injection of agglutinating and nonagglutinating strains into yellowtail, Seriola quinqueradiata Temminck & Schlegel, revealed that nonagglutinating strains were more virulent than agglutinating strains. Two nonagglutinating and highly pathogenic strains SS91-014 and SS91-092 were subcultured 30 times in brain heart infusion broth, and the agglutination titres of 50 colonies from subcultures 1, 2, 3, 4, 5, 6, 11, 16, 21, 26 and 30 against anti-YT-3 serum were determined. Transformation from a nonagglutinating (1 :<4) to an agglutinating (1 : >4) pattern was first observed at the sixteenth subculture, and the ratio of agglutinating to nonagglutinating substrains rose until the thirtieth subculture. At this time, 70% of the SS91-014 population and 52% of the SS91-092 population were transformed to an agglutinating pattern. When the pathogenicity of four transformed substrains with different agglutination titres was tested in yellowtail, the nonagglutinating substrain showed higher pathogenicity than the agglutinating substrains, but no relationship between LD
50 values and the agglutination titres of transformed substrains was observed. The pathogenicity of E. seriolicida appears to be related to the agglutination pattern, although it was not demonstrated that this property is solely responsible for pathogenicity. [ABSTRACT FROM AUTHOR]- Published
- 1996
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20. Studies on the pathogenesis of streptococcal infection in cultured yellowtails, Seriola spp.: effect of crude exotoxin fractions from cell-free culture on experimental streptococcal infection
- Author
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KIMURA, H., primary and KUSUDA, R., additional
- Published
- 1982
- Full Text
- View/download PDF
21. Studies on the pathogenesis of streptococcal infection in cultured yellowtails Seriola spp.: effect of the cell free culture on experimental streptococcal infection
- Author
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KIMURA, H., primary and KUSUDA, R., additional
- Published
- 1979
- Full Text
- View/download PDF
22. Changes in agglutinating antibody titers and serum proteins of immunized eels
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Kusuda, R, primary, Ono, K, additional, and Salati, F, additional
- Published
- 1988
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23. A detailed intake-status profiling of seafoods in adult food-protein-induced enterocolitis syndrome patients.
- Author
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Watanabe S, Sato A, Uga M, Matsukawa N, Kusuda R, Suzuki H, Nagashima S, Yauchi T, Ohya Y, and Nomura I
- Subjects
- Adult, Humans, Infant, Retrospective Studies, Dietary Proteins adverse effects, Syndrome, Allergens, Seafood adverse effects, Immunoglobulin E, Food Hypersensitivity, Enterocolitis diagnosis, Enterocolitis epidemiology
- Abstract
Background: Adults with food-protein-induced enterocolitis syndrome (FPIES) often develop severe abdominal symptoms after eating seafood. However, no investigation of a food elimination strategy for adult FPIES patients has been performed to date., Methods: We conducted a retrospective cohort study of seafood-avoidant adults by telephone interview, based on the diagnostic criteria for adult FPIES reported by González et al. We compared the clinical profiles, abdominal symptoms, and causative seafoods between FPIES and immediate-type food allergy (IgE-mediated FA) patients. We also profiled the detailed intake-status of seafoods in adult FPIES patients., Results: Twenty-two (18.8 %) of 117 adults with seafood-allergy were diagnosed with FPIES. Compared with the IgE-mediated FA patients, FPIES patients had an older age of onset, more pre-existing gastrointestinal and atopic diseases, more episodes, longer latency and duration of symptoms, more nausea, abdominal distention, and severe abdominal pain, and more frequent vomiting and diarrhea. In particular, abdominal distention-reflecting intestinal edema and luminal fluid retention-may be the most distinctive characteristic symptom in adult FPIES (p < 0.001). Bivalves, especially oysters, were the most common cause of FPIES. Strikingly, intake-status profiling revealed that many FPIES patients can safely ingest an average of 92.6 % of seafood species other than the causative species., Conclusions: There are many differentiators between FPIES and IgE-mediated FA, which may reflect differences in the underlying immunological mechanisms. Although seafood FPIES is unlikely to induce tolerance, many patients can ingest a wide variety of seafood species after a long period from onset., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. Comparison of adult food protein-induced enterocolitis syndrome to crustaceans and immediate-type food allergy.
- Author
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Watanabe S, Sato A, Uchida H, Kusuda R, Suzuki H, Nagashima S, Yauchi T, Matsumoto K, Ohya Y, and Nomura I
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- Animals, Humans, Adult, Infant, Retrospective Studies, Crustacea, Dietary Proteins, Allergens, Food Hypersensitivity, Hypersensitivity, Immediate complications, Enterocolitis diagnosis, Enterocolitis etiology
- Abstract
Background: Food protein-induced enterocolitis syndrome (FPIES) is increasingly found in adults. FPIES requires different treatment from immediate-type food allergy (FA) in emergency medicine. However, no comparison of the clinical presentations of these diseases has been reported., Objective: To compare the clinical presentations and causative crustaceans of adult FPIES and FA using a standardized questionnaire and to thereby lay the groundwork for establishing an algorithm that distinguishes those diseases., Methods: We conducted a retrospective cohort study of crustacean-avoidant adults by telephone interview based on the previously reported diagnostic criteria for adult FPIES to compare the clinical features and crustacean intake status between FPIES and FA., Results: Of 73 adult patients with crustacean allergy, 8 (11%) were diagnosed with having FPIES and 53 (73%) FA. Compared with the patients with FA, those with FPIES had a longer latency period (P < .01), more episodes (P = .02), longer duration of symptoms (P = .04), more frequent abdominal distention (P = .02), and severe colic pain (P = .02). Half of the patients with FPIES experienced fear of death during an episode. Panulirus japonicus (Japanese spiny lobster) and Homarus weber (lobster) were significantly common FPIES-causing foods. A statistically significant 62.5% of patients with FPIES were able to ingest some type of crustacean., Conclusion: FPIES and FA can be clearly differentiated by the abdominal symptoms, latency period, and duration of episodes. Furthermore, some patients with FPIES do not necessarily need to avoid all crustaceans. Our findings lay the groundwork for establishing an algorithm that distinguishes FPIES from FA in adults., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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25. Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice.
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Maganin AG, Souza GR, Fonseca MD, Lopes AH, Guimarães RM, Dagostin A, Cecilio NT, Mendes AS, Gonçalves WA, Silva CE, Fernandes Gomes FI, Mauriz Marques LM, Silva RL, Arruda LM, Santana DA, Lemos H, Huang L, Davoli-Ferreira M, Santana-Coelho D, Sant'Anna MB, Kusuda R, Talbot J, Pacholczyk G, Buqui GA, Lopes NP, Alves-Filho JC, Leão RM, O'Connor JC, Cunha FQ, Mellor A, and Cunha TM
- Subjects
- Animals, Mice, Quinolinic Acid metabolism, Metabolic Networks and Pathways, Dendritic Cells metabolism, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Kynurenine metabolism, Neuralgia
- Abstract
Neuropathic pain is one of the most important clinical consequences of injury to the somatosensory system. Nevertheless, the critical pathophysiological mechanisms involved in neuropathic pain development are poorly understood. In this study, we found that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO1-expressing dendritic cells (DCs) accumulated in the dorsal root leptomeninges and led to an increase in kynurenine levels in the spinal cord. In the spinal cord, kynurenine was metabolized by kynurenine-3-monooxygenase-expressing astrocytes into the pronociceptive metabolite 3-hydroxykynurenine. Ultimately, 3-hydroxyanthranilate 3,4-dioxygenase-derived quinolinic acid formed in the final step of the canonical KYNPATH was also involved in neuropathic pain development through the activation of the glutamatergic N-methyl-D-aspartate receptor. In conclusion, these data revealed a role for DCs driving neuropathic pain development through elevation of the KYNPATH. This paradigm offers potential new targets for drug development against this type of chronic pain.
- Published
- 2022
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26. Cfdp1 controls the cell cycle and neural differentiation in the zebrafish cerebellum and retina.
- Author
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Itoh T, Inoue S, Sun X, Kusuda R, Hibi M, and Shimizu T
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- Animals, Cell Cycle genetics, Cell Differentiation genetics, Cerebellum, Mitosis, Neurogenesis genetics, Retina, Zebrafish genetics
- Abstract
Background: Although the cell cycle and cell differentiation should be coordinately regulated to generate a variety of neurons in the brain, the molecules that are involved in this coordination still remain largely unknown. In this study, we analyzed the roles of a nuclear protein Cfdp1, which is thought to be involved in chromatin remodeling, in zebrafish neurogenesis., Results: Zebrafish cfdp1 mutants maintained the progenitors of granule cells (GCs) in the cerebellum, but showed defects in their differentiation to GCs. cfdp1 mutants showed an increase in phospho-histone 3 (pH 3)-positive cells and apoptotic cells, as well as a delayed cell cycle transition from the G2 to the M phase in the cerebellum. The inhibition of tp53 prevented apoptosis but not GC differentiation in the cfdp1 mutant cerebellum. A similar increase in apoptotic cells and pH 3-positive cells, and defective cell differentiation, were observed in the cfdp1 mutant retina. Although mitotic spindles formed, mitosis was blocked before anaphase in both the cerebellum and retina of cfdp1 mutant larvae. Furthermore, expression of the G2/mitotic-specific cyclin B1 gene increased in the cfdp1 mutant cerebellum., Conclusions: Our findings suggest that Cfdp1 regulates the cell cycle of neural progenitors, thereby promoting neural differentiation in the brain., (© 2021 American Association for Anatomy.)
- Published
- 2021
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27. Odontoblast TRPC5 channels signal cold pain in teeth.
- Author
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Bernal L, Sotelo-Hitschfeld P, König C, Sinica V, Wyatt A, Winter Z, Hein A, Touska F, Reinhardt S, Tragl A, Kusuda R, Wartenberg P, Sclaroff A, Pfeifer JD, Ectors F, Dahl A, Freichel M, Vlachova V, Brauchi S, Roza C, Boehm U, Clapham DE, Lennerz JK, and Zimmermann K
- Abstract
Teeth are composed of many tissues, covered by an inflexible and obdurate enamel. Unlike most other tissues, teeth become extremely cold sensitive when inflamed. The mechanisms of this cold sensation are not understood. Here, we clarify the molecular and cellular components of the dental cold sensing system and show that sensory transduction of cold stimuli in teeth requires odontoblasts. TRPC5 is a cold sensor in healthy teeth and, with TRPA1, is sufficient for cold sensing. The odontoblast appears as the direct site of TRPC5 cold transduction and provides a mechanism for prolonged cold sensing via TRPC5's relative sensitivity to intracellular calcium and lack of desensitization. Our data provide concrete functional evidence that equipping odontoblasts with the cold-sensor TRPC5 expands traditional odontoblast functions and renders it a previously unknown integral cellular component of the dental cold sensing system., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
- Published
- 2021
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28. Regulatory T cells counteract neuropathic pain through inhibition of the Th1 response at the site of peripheral nerve injury.
- Author
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Davoli-Ferreira M, de Lima KA, Fonseca MM, Guimarães RM, Gomes FI, Cavallini MC, Quadros AU, Kusuda R, Cunha FQ, Alves-Filho JC, and Cunha TM
- Subjects
- Animals, Hyperalgesia, Mice, Mice, Inbred C57BL, Sciatic Nerve, Th1 Cells, Neuralgia, Peripheral Nerve Injuries complications, T-Lymphocytes, Regulatory
- Abstract
The inflammatory/immune response at the site of peripheral nerve injury participates in the pathophysiology of neuropathic pain. Nevertheless, little is known about the local regulatory mechanisms underlying peripheral nerve injury that counteracts the development of pain. Here, we investigated the contribution of regulatory T (Treg) cells to the development of neuropathic pain by using a partial sciatic nerve ligation model in mice. We showed that Treg cells infiltrate and proliferate in the site of peripheral nerve injury. Local Treg cells suppressed the development of neuropathic pain mainly through the inhibition of the CD4 Th1 response. Treg cells also indirectly reduced neuronal damage and neuroinflammation at the level of the sensory ganglia. Finally, we identified IL-10 signaling as an intrinsic mechanism by which Treg cells counteract neuropathic pain development. These results revealed Treg cells as important inhibitory modulators of the immune response at the site of peripheral nerve injury that restrains the development of neuropathic pain. In conclusion, the boosting of Treg cell function/activity might be explored as a possible interventional approach to reduce neuropathic pain development after peripheral nerve damage.
- Published
- 2020
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29. IL-27 Counteracts Neuropathic Pain Development Through Induction of IL-10.
- Author
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Fonseca MM, Davoli-Ferreira M, Santa-Cecília F, Guimarães RM, Oliveira FFB, Kusuda R, Ferreira DW, Alves-Filho JC, Cunha FQ, and Cunha TM
- Subjects
- Animals, Biomarkers, Cytokines metabolism, Disease Models, Animal, Ganglia, Spinal, Interleukin-27 genetics, Male, Mice, Mice, Knockout, Microglia metabolism, Peripheral Nerve Injuries complications, Receptors, Interleukin genetics, Receptors, Interleukin metabolism, Spinal Cord metabolism, Spinal Cord physiopathology, Disease Susceptibility, Interleukin-10 metabolism, Interleukin-27 metabolism, Neuralgia etiology, Neuralgia metabolism
- Abstract
Neuroimmune-glia interactions have been implicated in the development of neuropathic pain. Interleukin-27 (IL-27) is a cytokine that presents regulatory activity in inflammatory conditions of the central nervous system. Thus, we hypothesized that IL-27 would participate in the neuropathic pain process. Here, we found that neuropathic pain caused by peripheral nerve injury (spared nerve injury model; SNI), was enhanced in IL-27-deficient
(-/-) mice, whereas nociceptive pain is similar to that of wild-type mice. SNI induced an increase in the expression of IL-27 and its receptor subunit ( Wsx1 ) in the sensory ganglia and spinal cord. IL-27 receptor was expressed mainly in resident macrophage, microglia, and astrocytes of the sensory ganglia and spinal cord, respectively. Finally, we identify that the antinociceptive effect of IL-27 was not observed in IL-10-/- mice. These results provided evidence that IL-27 is a cytokine produced after peripheral nerve injury that counteracts neuropathic pain development through induction of the antinociceptive cytokine IL-10. In summary, our study unraveled the role of IL-27 as a regulatory cytokine that counteracts the development of neuropathic pain after peripheral nerve damage. In conclusion, they indicate that immunotherapies based on IL-27 could emerge as possible therapeutic approaches for the prevention of neuropathic pain development after peripheral nerve injury., (Copyright © 2020 Fonseca, Davoli-Ferreira, Santa-Cecília, Guimarães, Oliveira, Kusuda, Ferreira, Alves-Filho, Cunha and Cunha.)- Published
- 2020
- Full Text
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30. Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive potassium channels pathway.
- Author
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Kusuda R, Carreira EU, Ulloa L, Cunha FQ, Kanashiro A, and Cunha TM
- Subjects
- Animals, Choline therapeutic use, Dinoprostone metabolism, Freund's Adjuvant, Male, Mice, Mice, Inbred BALB C, Choline pharmacology, Cyclic GMP metabolism, Hyperalgesia drug therapy, Inflammation drug therapy, KATP Channels metabolism, Nitric Oxide metabolism, alpha7 Nicotinic Acetylcholine Receptor agonists
- Abstract
New findings on neural regulation of immunity are allowing the design of novel pharmacological strategies to control inflammation and nociception. Herein, we report that choline, a 7-nicotinic acetylcholine receptor (α7nAChRs) agonist, prevents carrageenan-induced hyperalgesia without affecting inflammatory parameters (neutrophil migration or cytokine/chemokines production) or inducing sedation or even motor impairment. Choline also attenuates prostaglandin-E
2 (PGE2 )-induced hyperalgesia via α7nAChR activation and this antinociceptive effect was abrogated by administration of LNMMA (a nitric oxide synthase inhibitor), ODQ (an inhibitor of soluble guanylate cyclase; cGMP), andglibenclamide(an inhibitor of ATP-sensitive potassium channels). Furthermore, choline attenuates long-lasting Complete Freund's Adjuvant and incision-induced hyperalgesia suggesting its therapeutic potential to treat pain in rheumatoid arthritis or post-operative recovery, respectively. Our results suggest that choline modulates inflammatory hyperalgesia by activating the nitric oxide/cGMP/ATP-sensitive potassium channels without interfering in inflammatory events, and could be used in persistent pain conditions., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
31. The role of neutrophils in neuro-immune modulation.
- Author
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Kanashiro A, Hiroki CH, da Fonseca DM, Birbrair A, Ferreira RG, Bassi GS, Fonseca MD, Kusuda R, Cebinelli GCM, da Silva KP, Wanderley CW, Menezes GB, Alves-Fiho JC, Oliveira AG, Cunha TM, Pupo AS, Ulloa L, and Cunha FQ
- Subjects
- Animals, Humans, Immunity, Innate, Inflammation immunology, Neurotransmitter Agents immunology, Nociception, Pain immunology, Sensory Receptor Cells immunology, Neuroimmunomodulation, Neutrophils immunology
- Abstract
Neutrophils are peripheral immune cells that represent the first recruited innate immune defense against infections and tissue injury. However, these cells can also induce overzealous responses and cause tissue damage. Although the role of neutrophils activating the immune system is well established, only recently their critical implications in neuro-immune interactions are becoming more relevant. Here, we review several aspects of neutrophils in the bidirectional regulation between the nervous and immune systems. First, the role of neutrophils as a diffuse source of acetylcholine and catecholamines is controversial as well as the effects of these neurotransmitters in neutrophil's functions. Second, neutrophils contribute for the activation and sensitization of sensory neurons, and thereby, in events of nociception and pain. In addition, nociceptor activation promotes an axon reflex triggering a local release of neural mediators and provoking neutrophil activation. Third, the recruitment of neutrophils in inflammatory responses in the nervous system suggests these immune cells as innovative targets in the treatment of central infectious, neurological and neurodegenerative disorders. Multidisciplinary studies involving immunologists and neuroscientists are required to define the role of the neurons-neutrophils communication in the pathophysiology of infectious, inflammatory, and neurological disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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32. Frontline Science: Blood-circulating leukocytes fail to infiltrate the spinal cord parenchyma after spared nerve injury.
- Author
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Guimarães RM, Davoli-Ferreira M, Fonseca MM, Damasceno LEA, Santa-Cecilia FV, Kusuda R, Menezes GB, Cunha FQ, Alves-Filho JC, and Cunha TM
- Subjects
- Animals, Cell Proliferation, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental blood, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental pathology, Endothelium, Vascular pathology, Female, Hematopoietic Stem Cells metabolism, Hyperalgesia blood, Hyperalgesia complications, Hyperalgesia immunology, Hyperalgesia pathology, Male, Mice, Inbred C57BL, Microglia pathology, Monocytes pathology, Neuralgia blood, Neuralgia complications, Neuralgia immunology, Neuralgia pathology, Receptors, CCR2 deficiency, Receptors, CCR2 metabolism, Leukocytes pathology, Peripheral Nerve Injuries blood, Peripheral Nerve Injuries pathology, Spinal Cord pathology
- Abstract
The development of neuropathic pain after peripheral nerve injury involves neuroimmune-glial interactions in the spinal cord. However, whether the development of neuropathic pain depends on the infiltration of peripheral immune cells, such as monocytes, into the spinal cord parenchyma after peripheral nerve damage remains unclear. Here, we used a combination of different techniques such as transgenic reporter mouse (Cx3cr1
GFP/+ and Ccr2RFP/+ mice), bone marrow chimeric mice, and parabiosis to investigate this issue in spared nerve injury (SNI) model. Herein, we provided robust evidence that, although microglial cells are activated/proliferate at the dorsal horn of the spinal cord after SNI, peripheral hematopoietic cells (including monocytes) are not able to infiltrate into the spinal cord parenchyma. Furthermore, there was no evidence of CCR2 expression in intrinsic cells of the spinal cord. However, microglial cells activation/proliferation in the spinal cord and mechanical allodynia after SNI were reduced in Ccr2-deficient mice. These results suggest that blood-circulating leukocytes cells are not able to infiltrate the spinal cord parenchyma after distal peripheral nerve injury. Nevertheless, they indicate that CCR2-expressing cells might be indirectly regulating microglia activation/proliferation in the spinal cord after SNI. In conclusion, our study supports that CCR2 inhibition could be explored as an interventional approach to reduce microglia activation and consequently neuropathic pain development after peripheral nerve injury., (©2019 Society for Leukocyte Biology.)- Published
- 2019
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33. Non-Peptidergic Nociceptive Neurons Are Essential for Mechanical Inflammatory Hypersensitivity in Mice.
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Pinto LG, Souza GR, Kusuda R, Lopes AH, Sant'Anna MB, Cunha FQ, Ferreira SH, and Cunha TM
- Subjects
- Animals, Dinoprostone metabolism, Glial Cell Line-Derived Neurotrophic Factor pharmacology, Hypersensitivity complications, Hypersensitivity physiopathology, Inflammation complications, Inflammation physiopathology, Lectins pharmacology, Male, Mice, Inbred C57BL, Nerve Fibers, Unmyelinated metabolism, Nociception drug effects, Nociceptors drug effects, Pain complications, Pain physiopathology, Saporins pharmacology, Hypersensitivity pathology, Inflammation pathology, Nociceptors pathology, Peptides metabolism
- Abstract
Small nerve fibers that bind the isolectin B4 (IB4
+ C-fibers) are a subpopulation of primary afferent neurons that are involved in nociceptive sensory transduction and do not express the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Several studies have attempted to elucidate the functional role of IB4+ -nociceptors in different models of pain. However, a functional characterization of the non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice is still lacking. To this end, in the present study, the neurotoxin IB4-Saporin (IB4-Sap) was employed to ablate non-peptidergic C-fibers. Firstly, we showed that intrathecal (i.t.) administration of IB4-Sap in mice depleted non-peptidergic C-fibers, since it decreased the expression of purinoceptor 3 (P2X3 ) and transient receptor potential cation channel subfamily V member 1 (TRPV1) in the dorsal root ganglia (DRGs) as well as IB4 labelling in the spinal cord. Non-peptidergic C-fibers depletion did not alter the mechanical nociceptive threshold, but it inhibited the mechanical inflammatory hypersensitivity induced by glial cell-derived neurotrophic factor (GDNF), but not nerve growth factor (NGF). Depletion of non-peptidergic C-fibers abrogated mechanical inflammatory hypersensitivity induced by carrageenan. Finally, it was found that the inflammatory mediators PGE2 and epinephrine produced a mechanical inflammatory hypersensitivity that was also blocked by depletion of non-peptidergic C-fibers. These data suggest that IB4-positive nociceptive nerve fibers are not involved in normal mechanical nociception but are sensitised by inflammatory stimuli and play a crucial role in mediating mechanical inflammatory hypersensitivity.- Published
- 2019
- Full Text
- View/download PDF
34. Dynamic expression of glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 in the mouse spinal cord dorsal horn under pathological pain states.
- Author
-
Turcato F, Almeida C, Mota C, Kusuda R, Carvalho A, Nascimento GC, Zanon S, Leite-Panissi CR, and Lucas G
- Subjects
- Animals, Disease Models, Animal, Down-Regulation, Inflammation complications, Inflammation physiopathology, Male, Mice, Muscles physiopathology, Sciatic Nerve injuries, Skin physiopathology, Up-Regulation, Calcium-Binding Proteins biosynthesis, Chronic Pain metabolism, Glial Fibrillary Acidic Protein biosynthesis, Inflammation metabolism, Microfilament Proteins biosynthesis, Neuralgia metabolism, Spinal Cord Dorsal Horn metabolism
- Abstract
Objective: Animal models of chronic pain have demonstrated that glial cells are promising target for development of analgesic drugs. However, preclinical studies on glial response under chronic pain conditions vary depending on the cellular markers, the species used, the experimental design and model. Therefore, we investigate the expression profile of GFAP and Iba-1 during the behavioral manifestation of sensory disorder in inflammatory and neuropathic pain models. Methods: the expression profile of fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) were quantitated in the spinal dorsal horn of Balb/C mice submitted to six models of chronic pain. Protein analysis was performed by western blot and the results colligated with pain-related behavior. Results: Using the same method to quantitate proteins we observed that while GFAP is upregulated after axotomy, partial nerve injury and cutaneous inflammation, its expression is not changed during muscle inflammation, non-inflammatory muscle pain, and in a viral-associated pain. Differently, Iba-1 is downregulated after axotomy but upregulated after partial lesion of peripheral nerve as well as after virus inoculation and during non-inflammatory muscle pain. Cutaneous and muscle inflammation induced no change in Iba-1 expression in the dorsal horn.In spite of a marked time-dependent variation in protein expression, mechanical allodynia was present at any time of all the models investigated. Discussion: Under distinct pain conditions, GFAP and Iba-1 expression is dependent on the origin of the stimulus, disease progression and tissue affected. Moreover, their expression and is not necessarily associated to the behavior manifestation of pain.
- Published
- 2019
- Full Text
- View/download PDF
35. The NOD2 signaling in peripheral macrophages contributes to neuropathic pain development.
- Author
-
Santa-Cecília FV, Ferreira DW, Guimaraes RM, Cecilio NT, Fonseca MM, Lopes AH, Davoli-Ferreira M, Kusuda R, Souza GR, Nachbur U, Alves-Filho JC, Teixeira MM, Zamboni DS, Cunha FQ, and Cunha TM
- Subjects
- Animals, Bone Marrow Transplantation, Carrageenan toxicity, Disease Models, Animal, Inflammation chemically induced, Inflammation therapy, Interleukin 1 Receptor Antagonist Protein therapeutic use, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Minocycline therapeutic use, Neuralgia genetics, Neuralgia surgery, Neuroprotective Agents therapeutic use, Nod2 Signaling Adaptor Protein genetics, RNA, Small Interfering therapeutic use, Receptor-Interacting Protein Serine-Threonine Kinase 2, Receptor-Interacting Protein Serine-Threonine Kinases genetics, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, Receptors, Tumor Necrosis Factor, Type I genetics, Receptors, Tumor Necrosis Factor, Type I metabolism, Signal Transduction genetics, Signal Transduction physiology, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Xanthines therapeutic use, Macrophages metabolism, Neuralgia pathology, Neuralgia physiopathology, Nod2 Signaling Adaptor Protein metabolism
- Abstract
Neuropathic pain is one of the most important types of chronic pain. It is caused by neuronal damage. Clinical and experimental studies suggest a critical role for neuroimmune interactions in the development of neuropathic pain. In this article, we have shown that the cytoplasmic receptor Nod-like receptor-2, NOD2, and its adaptor-signaling molecule RIPK2 participate in the development of neuropathic pain after peripheral nerve injury (spared nerve injury model). The activation of NOD2 signaling in peripheral macrophage mediates the development of neuropathic pain through the production of pronociceptive cytokines (tumor necrosis factor and IL-1β). This study found that peripheral nerve injury promoted a systemic increase in the NOD2 ligand. These results highlight a previously undetermined role for NOD2 signaling in the development of neuropathic pain, suggesting a new potential target for preventing neuropathic pain.
- Published
- 2019
- Full Text
- View/download PDF
36. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1.
- Author
-
Nersesyan Y, Demirkhanyan L, Cabezas-Bratesco D, Oakes V, Kusuda R, Dawson T, Sun X, Cao C, Cohen AM, Chelluboina B, Veeravalli KK, Zimmermann K, Domene C, Brauchi S, and Zakharian E
- Subjects
- Animals, Calcium metabolism, Capsaicin analogs & derivatives, Capsaicin pharmacology, Cells, Cultured, Evoked Potentials drug effects, Female, Ganglia, Spinal cytology, HEK293 Cells, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons cytology, Neurons drug effects, Neurons metabolism, Protein Structure, Quaternary, Receptors, Oxytocin antagonists & inhibitors, Receptors, Oxytocin genetics, Receptors, Oxytocin metabolism, TRPV Cation Channels agonists, TRPV Cation Channels antagonists & inhibitors, TRPV Cation Channels metabolism, Nociception drug effects, Oxytocin pharmacology, TRPV Cation Channels genetics
- Abstract
Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
37. Medial plantar nerve ligation as a novel model of neuropathic pain in mice: pharmacological and molecular characterization.
- Author
-
Sant'Anna MB, Kusuda R, Bozzo TA, Bassi GS, Alves-Filho JC, Cunha FQ, Ferreira SH, Souza GR, and Cunha TM
- Subjects
- Activating Transcription Factor 3 genetics, Activating Transcription Factor 3 metabolism, Amines pharmacology, Analgesics pharmacology, Animals, Cyclohexanecarboxylic Acids pharmacology, Gabapentin, Gene Expression Regulation, Humans, Hyperalgesia metabolism, Hyperalgesia prevention & control, Interleukin-6 genetics, Interleukin-6 metabolism, Ligation, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuralgia drug therapy, Neuralgia metabolism, Neuroglia drug effects, Neuroglia metabolism, Neuroglia pathology, Sensory Receptor Cells drug effects, Sensory Receptor Cells metabolism, Sensory Receptor Cells pathology, Spinal Cord drug effects, Spinal Cord metabolism, Spinal Cord physiopathology, Tibial Nerve drug effects, Tibial Nerve injuries, Tibial Nerve metabolism, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, gamma-Aminobutyric Acid pharmacology, Disease Models, Animal, Hyperalgesia physiopathology, Motor Activity physiology, Neuralgia physiopathology, Tibial Nerve physiopathology
- Abstract
Peripheral neuropathic pain is a consequence of an injury/disease of the peripheral nerves. The mechanisms involved in its pathophysiology are not entirely understood. To better understand the mechanisms involved in the development of peripheral nerve injury-induced neuropathic pain, more experimental models are required. Here, we developed a novel peripheral neuropathic pain model in mice by using a minimally invasive surgery and medial plantar nerve ligation (MPNL). After MPNL, mechanical allodynia was established, and mice quickly recovered from the surgery without any significant motor impairment. MPNL causes an increased expression of ATF-3 in the sensory neurons. At 14 days after surgery, gabapentin was capable of reversing the mechanical allodynia, whereas anti-inflammatory drugs and opioids were ineffective. MPNL-induced neuropathic pain was mediated by glial cells activation and the production of TNF-α and IL-6 in the spinal cord. These results indicate MPNL as a reasonable animal model for the study of peripheral neuropathic pain, presenting analgesic pharmacological predictivity to clinically used drugs. The results also showed molecular phenotypic changes similar to other peripheral neuropathic pain models, with the advantage of a lack of motor impairment. These features indicate that MPNL might be more appropriate for the study of neuropathic pain than classical models.
- Published
- 2016
- Full Text
- View/download PDF
38. Dynamic weight bearing is an efficient and predictable method for evaluation of arthritic nociception and its pathophysiological mechanisms in mice.
- Author
-
Quadros AU, Pinto LG, Fonseca MM, Kusuda R, Cunha FQ, and Cunha TM
- Subjects
- Analgesics pharmacology, Animals, Arthritis, Experimental pathology, Astrocytes pathology, Interleukin-1beta immunology, Male, Mice, Mice, Inbred BALB C, Microglia pathology, Tumor Necrosis Factor-alpha immunology, Weight-Bearing, Arthritis, Experimental immunology, Arthritis, Experimental physiopathology, Astrocytes immunology, Microglia immunology, Nociception
- Abstract
The assessment of articular nociception in experimental animals is a challenge because available methods are limited and subject to investigator influence. In an attempt to solve this problem, the purpose of this study was to establish the use of dynamic weight bearing (DWB) as a new device for evaluating joint nociception in an experimental model of antigen-induced arthritis (AIA) in mice. AIA was induced in Balb/c and C57BL/6 mice, and joint nociception was evaluated by DWB. Western Blotting and real-time PCR were used to determine protein and mRNA expression, respectively. DWB detected a dose- and time-dependent increase in joint nociception during AIA and was able to detect the dose-response effects of different classes of analgesics. Using DWB, it was possible to evaluate the participation of spinal glial cells (microglia and astrocytes) and cytokines (IL-1β and TNFα) for the genesis of joint nociception during AIA. In conclusion, the present results indicated that DWB is an effective, objective and predictable test to study both the pathophysiological mechanisms involved in arthritic nociception in mice and for evaluating novel analgesic drugs against arthritis.
- Published
- 2015
- Full Text
- View/download PDF
39. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain.
- Author
-
Almeida C, DeMaman A, Kusuda R, Cadetti F, Ravanelli MI, Queiroz AL, Sousa TA, Zanon S, Silveira LR, and Lucas G
- Subjects
- Adaptation, Physiological, Animals, CREB-Binding Protein metabolism, Citrate (si)-Synthase, Disease Models, Animal, Glial Fibrillary Acidic Protein metabolism, Heart physiopathology, Hyperalgesia etiology, Male, Mice, Mice, Inbred BALB C, Muscle, Skeletal physiopathology, Neuralgia complications, Neuralgia pathology, Neuroglia pathology, Pain Measurement, Pain Threshold physiology, Phospholipase C gamma metabolism, Phosphorylation, Time Factors, Brain-Derived Neurotrophic Factor metabolism, Exercise Therapy methods, Neuralgia rehabilitation, Neuroglia metabolism, Up-Regulation physiology
- Abstract
Treatment of neuropathic pain is a clinical challenge likely because of the time-dependent changes in many neurotransmitter systems, growth factors, ionic channels, membrane receptors, transcription factors, and recruitment of different cell types. Conversely, an increasing number of reports have shown the ability of extended and regular physical exercise in alleviating neuropathic pain throughout a wide range of mechanisms. In this study, we investigate the effect of swim exercise on molecules associated with initiation and maintenance of nerve injury-induced neuropathic pain. BALB/c mice were submitted to partial ligation of the sciatic nerve followed by a 5-week aerobic exercise program. Physical training reversed mechanical hypersensitivity, which lasted for an additional 4 weeks after exercise interruption. Swim exercise normalized nerve injury-induced nerve growth factor, and brain-derived neurotrophic factor (BDNF) enhanced expression in the dorsal root ganglion, but had no effect on the glial-derived neurotrophic factor. However, only BDNF remained at low levels after exercise interruption. In addition, exercise training significantly reduced the phosphorylation status of PLCγ-1, but not CREB, in the spinal cord dorsal horn in response to nerve injury. Finally, prolonged swim exercise reversed astrocyte and microglia hyperactivity in the dorsal horn after nerve lesion, which remained normalized after training cessation. Together, these results demonstrate that exercise therapy induces long-lasting analgesia through various mechanisms associated with the onset and advanced stages of neuropathy. Moreover, the data support further studies to clarify whether appropriate exercise intensity, volume, and duration can also cause long-lasting pain relief in patients with neuropathic pain.
- Published
- 2015
- Full Text
- View/download PDF
40. Six New Polyacetylenic Alcohols from the Marine Sponges Petrosia sp. and Halichondria sp.
- Author
-
Gabriel AF, Li Z, Kusuda R, Tanaka C, and Miyamoto T
- Subjects
- Alcohols isolation & purification, Alcohols pharmacology, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents isolation & purification, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, HeLa Cells, Humans, Neoplasms drug therapy, Polyynes isolation & purification, Polyynes pharmacology, Alcohols chemistry, Petrosia chemistry, Polyynes chemistry, Porifera chemistry
- Abstract
Six new polyacetylenic alcohols, termed strongylotriols A and B; pellynols J, K, and L; and isopellynol A, together with three known polyacetylenic alcohols, pellynols A, B, and C were isolated from the marine sponges Petrosia sp., and Halichondria sp. collected in Okinawa, Japan. Their planer structures were determined based on 2D-NMR and mass spectrometric analysis of the degraded products by RuCl3 oxidation. The absolute stereochemistry of isolates was examined by their Mosher's esters. The strongylotriols were found to be optically pure compounds, whereas the pellynols are diastereomeric mixtures at the C-6 position. Proliferation experiments using the HeLa and K562 cell lines suggested that the essential structural units for activity are the "hexa-2,4-diyn-1,6-diol" and "pent-1-en-4-yn-3-ol" on the termini.
- Published
- 2015
- Full Text
- View/download PDF
41. Long-term antidepressant treatment inhibits neuropathic pain-induced CREB and PLCγ-1 phosphorylation in the mouse spinal cord dorsal horn.
- Author
-
Kusuda R, Ravanelli MI, Cadetti F, Franciosi A, Previdelli K, Zanon S, and Lucas G
- Subjects
- Animals, Antidepressive Agents, Tricyclic therapeutic use, Behavior, Animal drug effects, Blotting, Western, Imipramine therapeutic use, Immunohistochemistry, MAP Kinase Signaling System drug effects, Male, Mice, Mice, Inbred BALB C, Mitogen-Activated Protein Kinases metabolism, Pain Measurement drug effects, Phosphorylation drug effects, Sciatica drug therapy, Sciatica pathology, p38 Mitogen-Activated Protein Kinases metabolism, Antidepressive Agents therapeutic use, Cyclic AMP Response Element-Binding Protein metabolism, Neuralgia drug therapy, Neuralgia metabolism, Phospholipase C gamma metabolism, Posterior Horn Cells metabolism
- Abstract
Unlabelled: The effect of long-term administration of imipramine, a tricyclic antidepressant, on the phosphorylation status of cyclic adenosine monophosphate-responsive element-binding protein (CREB), mitogen-activated protein kinase family members, and phospholipase γ-1 (PLCγ-1) was investigated in the dorsal horn of the spinal cord following peripheral nerve lesion. Nerve injury induced an ipsilateral long-lasting increased phosphorylation of CREB and PLCγ-1 but not extracellular signal-regulated kinase (ERK1,2), p38, and c-Jun N-terminal kinase. Daily administration of imipramine (5, 10, or 30 mg/kg) for 21 days progressively reduced both tactile-induced neuropathic pain hypersensitivity and thermal hyperalgesia. After withdrawal of treatment, the antinociceptive effect of imipramine was gradually abolished but still remained for at least 3 weeks. Conversely, no analgesic effect was observed with short-term imipramine treatment. Moreover, imipramine therapy reversed nerve injury-induced CREB and PLCγ-1 phosphorylation but had no effect on ERK1,2, p38, and c-Jun N-terminal kinase activity. These results indicate that long-term administration of imipramine may prevent some of the harmful changes in the spinal cord dorsal horn following nerve injury. However, imipramine analgesic effect takes time to develop and mature, which might explain in part why the clinical analgesic effect of tricyclic antidepressants develops with a delay after the beginning of treatment. Our data also provide evidence that prolonged imipramine treatment may induce antinociception in neuropathic pain conditions because of its action on the PLCγ-1/CREB-signaling pathway., Perspective: This article demonstrates that long-term treatment with imipramine reverses some of the marked effects induced by peripheral nerve injury in the spinal dorsal horn that contribute to long-term maintenance of sensory disorder, providing a new view to the mechanisms of action of these drugs., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
42. Differential expression of microRNAs in mouse pain models.
- Author
-
Kusuda R, Cadetti F, Ravanelli MI, Sousa TA, Zanon S, De Lucca FL, and Lucas G
- Subjects
- Animals, Disease Models, Animal, Ganglia, Spinal metabolism, Mice, Mice, Inbred BALB C, Posterior Horn Cells metabolism, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs genetics, Pain genetics
- Abstract
Background: MicroRNAs (miRNAs) are short non-coding RNAs that inhibit translation of target genes by binding to their mRNAs. The expression of numerous brain-specific miRNAs with a high degree of temporal and spatial specificity suggests that miRNAs play an important role in gene regulation in health and disease. Here we investigate the time course gene expression profile of miR-1, -16, and -206 in mouse dorsal root ganglion (DRG), and spinal cord dorsal horn under inflammatory and neuropathic pain conditions as well as following acute noxious stimulation., Results: Quantitative real-time polymerase chain reaction analyses showed that the mature form of miR-1, -16 and -206, is expressed in DRG and the dorsal horn of the spinal cord. Moreover, CFA-induced inflammation significantly reduced miRs-1 and -16 expression in DRG whereas miR-206 was downregulated in a time dependent manner. Conversely, in the spinal dorsal horn all three miRNAs monitored were upregulated. After sciatic nerve partial ligation, miR-1 and -206 were downregulated in DRG with no change in the spinal dorsal horn. On the other hand, axotomy increases the relative expression of miR-1, -16, and 206 in a time-dependent fashion while in the dorsal horn there was a significant downregulation of miR-1. Acute noxious stimulation with capsaicin also increased the expression of miR-1 and -16 in DRG cells but, on the other hand, in the spinal dorsal horn only a high dose of capsaicin was able to downregulate miR-206 expression., Conclusions: Our results indicate that miRNAs may participate in the regulatory mechanisms of genes associated with the pathophysiology of chronic pain as well as the nociceptive processing following acute noxious stimulation. We found substantial evidence that miRNAs are differentially regulated in DRG and the dorsal horn of the spinal cord under different pain states. Therefore, miRNA expression in the nociceptive system shows not only temporal and spatial specificity but is also stimulus-dependent., (© 2011 Kusuda et al; licensee BioMed Central Ltd.)
- Published
- 2011
- Full Text
- View/download PDF
43. The analysis of immune responses of a novel CC-chemokine gene from Japanese flounder Paralichthys olivaceus.
- Author
-
Kono T, Kusuda R, Kawahara E, and Sakai M
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cell Separation, Chemotaxis, Leukocyte immunology, Cloning, Molecular, DNA genetics, DNA immunology, Enzyme-Linked Immunosorbent Assay, Humans, Macrophages immunology, Mice, Molecular Sequence Data, Phagocytosis immunology, Phylogeny, Plasmids genetics, Plasmids immunology, Promoter Regions, Genetic genetics, Reverse Transcriptase Polymerase Chain Reaction, Superoxides immunology, Chemokines, CC genetics, Chemokines, CC immunology, Flounder immunology
- Abstract
A novel CC-chemokine gene was isolated from the Japanese flounder Paralichthys olivaceus by expressed sequence tag analysis. The function of this CC-chemokine gene was studied by DNA injection. To investigate the immune responses to the CC-chemokine, a plasmid construct containing the novel CC-chemokine and a CMV promoter was injected into the epaxial muscle of Japanese flounder. Quantification of CC-chemokine protein expressed in serum on 1, 3 and 5 days after plasmid injection were estimated by ELISA. CC-chemokine gene injection increased the migration of phagocytic cells. Macrophage functions such as production of superoxide anion and phagocytosis were also stimulated by this gene injection. Thus, this gene from Japanese flounder has functional similarities to that of a mammalian CC-chemokine gene.
- Published
- 2003
- Full Text
- View/download PDF
44. G1 antigen: a cell-surface immunoprotective 96 kDa glycoprotein from the virulent fish pathogen Enterococcus seriolicida, its purification and characterization.
- Author
-
Alim SR, Hossain MA, Chowdhury EK, and Kusuda R
- Subjects
- Animals, Antigens, Bacterial immunology, Antigens, Surface immunology, Antigens, Surface isolation & purification, Bacterial Proteins immunology, Enterococcus pathogenicity, Fish Diseases, Glycoproteins isolation & purification, Immunodominant Epitopes immunology, Immunodominant Epitopes isolation & purification, Immunologic Techniques, Virulence, Antigens, Bacterial isolation & purification, Bacterial Proteins isolation & purification, Enterococcus immunology, Enterococcus isolation & purification, Fishes microbiology, Glycoproteins immunology
- Abstract
Strains of the fish pathogen Enterococcus seriolicida were identified as agglutinating and non-agglutinating, according to their reaction with anti-serum raised against type strain YT-3 (ATCC49156). The non-agglutinating strains are highly pathogenic in contrast to agglutinating strains. A 96 kDa immunoprotective glycoprotein G1 antigen from non-agglutinating Ent. seriolicida strain SS91-014 (N) was purified and characterized. The purification procedure entailed extraction of antigen by glass bead agitation, 80% (NH4)(2)SO4 precipitation, gel filtration and electroelution. An immunofluorescence microscopy study using monoclonal antibody M3A5 raised against G1 antigen revealed that G1 antigen is present only on the cell surface of non-agglutinating strains. Therefore, the G1 antigen of virulent Ent. seriolicida could be a potential candidate for protective vaccine against enterococcosis in fish.
- Published
- 2001
- Full Text
- View/download PDF
45. Cross-reactivity of anti-yellowtail thymic lymphocyte monoclonal antibody (YeT-2) with lymphocytes from other fish species.
- Author
-
Nishimura H, Ikemoto M, Kawai K, and Kusuda R
- Subjects
- Animals, Antibodies, Monoclonal, Antigens chemistry, Blotting, Western, Cross Reactions, Flow Cytometry, Kidney cytology, Lymphocytes ultrastructure, Species Specificity, Spleen cytology, Fishes immunology, Lymphocytes immunology, Thymus Gland cytology
- Abstract
The monoclonal antibody YeT-2, generated in mice hyper-immunized with thymic lymphocytes of the yellowtail, Seriola quinqueradiata, reacts with the major population of peripheral blood lymphocytes, which might be putative T cells. In this study, we examined the cross-reactivity of YeT-2 with lymphocytes from various fish species. Flow cytometric analysis showed that YeT-2 reacts with 69.8% lymphocytes in the thymus, 89.7% in the peripheral blood, 87.5% in the spleen, and 59.7% in the head-kidney. Among the six fish species examined, only the red sea bream, Pagrus major, which is included in the same suborder Percoidei with the yellowtail, showed the presence of YeT-2 positive cells. Electron microscopic studies revealed that YeT-2 positive cells in the peripheral blood of the red sea bream were lymphocytes or unidentified leucocytes. Thymic lymphocytes of the red sea bream were also immunocytochemically stained with YeT-2. The molecular weight of the YeT-2 cross-reacting antigen on blood cells from the red sea bream was identical with that from the yellowtail, which was identified at approximately 115 kDa. These results suggest that the monoclonal antibody YeT-2 recognizes a conserved antigen on lymphocytes common to the red sea bream and yellowtail.
- Published
- 1997
- Full Text
- View/download PDF
46. Development of DNA diagnostic methods for the detection of new fish iridoviral diseases.
- Author
-
Tamai T, Tsujimura K, Shirahata S, Oda H, Noguchi T, Kusuda R, Sato N, Kimura S, Katakura Y, and Murakami H
- Subjects
- Animals, Cloning, Molecular, Consensus Sequence, DNA Primers, Fishes, Genome, Viral, Immunoblotting, Molecular Sequence Data, Nucleic Acid Hybridization, Polymerase Chain Reaction, Ranavirus genetics, Sensitivity and Specificity, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, DNA, Viral analysis, Fish Diseases diagnosis, Fish Diseases virology, Iridoviridae genetics, Virus Diseases diagnosis
- Abstract
A new disease of epidemic proportions caused by fish viruses within the Iridoviridae family inflicts serious damage on red sea breams (Pagrus major) and striped jack (Caranx delicatissimus) populations grown in aquacultures in Japan. A partial segment of the fish iridoviral DNA was directly amplified using the polymerase chain reaction (PCR) with synthetic primers designed from well conserved nucleotide sequences between the frog virus 3 (Ranavirus) and the silkworm iridescent virus type 6. The deduced amino acid sequence from the nucleotide sequence of the PCR fragment demonstrates a high correlation with a partial sequence from the frog virus 3. Using the PCR method with specific primers, we could detect three of four different known types of fish iridoviruses in diseased fishes. To construct more reliable detection methods specific for this viral family, DNA fragments which can specifically hybridize with all of the four known iridoviridae viral DNAs were screened from the genomic library of one iridoviridae strain. The hybridization assay, using a specific fragment which contains regions which are highly homologous with a characterized partial sequence from the frog virus 3, proved to be a reliable diagnostic tool for fish iridoviral diseases.
- Published
- 1997
- Full Text
- View/download PDF
47. Characteristics of porin-like major outer membrane proteins of Listonella anguillara serotypes J-O-1, -2 and -3.
- Author
-
Suzuki S, Kuroe K, and Kusuda R
- Subjects
- Antigens, Bacterial chemistry, Antigens, Bacterial isolation & purification, Bacterial Outer Membrane Proteins chemistry, Blotting, Western, Electrophoresis, Polyacrylamide Gel, Escherichia coli chemistry, Molecular Weight, Porins isolation & purification, Ultracentrifugation, Vibrio classification, Porins chemistry, Vibrio chemistry
- Abstract
Major outer membrane protein (MOMP) was prepared from fish pathogen Listonella anguillara. Triton X-100 treatment could extract the MOMP from the bacterium but not from Escherichia coli, suggesting loose association of the MOMP of L. anguillara to the membrane. Properties of purified MOMP from L. anguillara were similar to Omp C porin of E. coli. Similar antigenicity of the porin like-MOMP was found among different serotypes of L. anguillara, although the molecular sizes of the MOMP were different among the strains.
- Published
- 1994
48. Lymphomyeloid cells, susceptibility to erythrodermatitis of carp and bacterial antigens.
- Author
-
Sövényi JF, Yamamoto H, Fujimoto S, and Kusuda R
- Subjects
- Animals, Bacterial Infections immunology, Blood Cell Count veterinary, Flow Cytometry, Kidney pathology, Lipopolysaccharides immunology, Phagocytosis, Skin Diseases, Infectious immunology, Spleen pathology, Aeromonas immunology, Antigens, Bacterial immunology, Bacterial Infections veterinary, Carps immunology, Cyprinidae immunology, Fish Diseases immunology, Skin Diseases, Infectious veterinary
- Abstract
Pronounced changes occur in the kidneys carp injected with extracellular product (ECP), lipopolysaccharide (LPS) of A. salmonicida subsp. salmonicida, Freund's complete adjuvant (FCA). ECP caused 50-70% decrease in macrophages and neutrophils, whereas blasts and lymphocyte-like cells increased FCA-elicited increased percentages of blasts and a left shift of neutrophils after LPS injection. After both ECP and FCA injections, the density of major leucocyte types and red blood cells (RBC) in the kidney decreased. LPS generally increased the density of leucocytes. Granulocytes were larger after LPS injection and smaller after FCA injection than control cells. Perhaps ECP eliminates those cells potentially capable of nonspecific defense and FCA stimulates their proliferation. LPS seemed to induce mainly polyclonal lymphocyte-like cell propagation and a reduced replenishment of other leucocytes. Challenge morbidity was 100% of ECP-injected groups, 54.3% of controls, 37.1% of LPS-injected fish and 11.4% of FCA-injected groups. Disease susceptibility may be correlated with availability and functional status of macrophages and neutrophils.
- Published
- 1990
- Full Text
- View/download PDF
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