RESUMO
In the current study, carrageenan (CG; 100-1000 µg/site) was injected intraorally in the cheeks of Holtzman or Wistar rats to evaluate the consequences of administration of a non-immunogenic stimulus in the orofacial region. Subsequent inflammation was measured as oedema (increased thickness of the cheek wall using digital calipers), relative to the other cheek injected with saline. Oedema formation and tissue collection for histopathological studies were assessed at 0.5, 1, 2, 3, 4, 6, 24, 48, 72, 96, 120 and 144 h after injection. In parallel, other groups of rats were injected with CG in the hind paw, to provide a reference response. The inhibitor of prostaglandin biosynthesis, indomethacin, and antagonists of histamine, serotonin and NK1 receptors were injected s.c., 0.5 h before CG. CG induced a dose-related oedema more rapidly from 0 to 2 h which lasted for at least 72 h, showing a biphasic profile (peak at 2 and 24 h), compared with the monophasic oedema induced in rat paws (maximal duration of 24 h). Histopathological analysis of the CG-injected cheek revealed oedema formation with little leukocyte recruitment at 1-3 h, mast cell degranulation at 6 h, and a mixed polymorphonuclear and mononuclear cell infiltrate by 24 h. Histamine and serotonin antagonists and indomethacin, but not the NK1 antagonist, decreased cheek oedema in the first 4 h following carrageenan. Taken together, our data indicated important differences in the pattern of inflammation between the oral cavity and the paw which will determine the therapeutic approach to the treatment of inflammatory conditions in the oral cavity.
Assuntos
Carragenina/administração & dosagem , Modelos Animais de Doenças , Edema/imunologia , Boca/imunologia , Animais , Bochecha , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/metabolismo , Edema/prevenção & controle , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Indometacina/administração & dosagem , Indometacina/uso terapêutico , Boca/efeitos dos fármacos , Boca/metabolismo , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Ratos Sprague-Dawley , Ratos Wistar , Antagonistas da Serotonina/administração & dosagem , Antagonistas da Serotonina/uso terapêuticoRESUMO
Host responses to synthetic implants are analogous to healing, the process of repair that follows injury. Normally, the processes of wound healing follow well-established patterns but conditions such as autoimmune diseases profoundly affect tissue repair. We have analyzed sponge-induced wound healing responses in lupus-prone New Zealand White and control (Balb/c) mouse strains by measuring inflammation, extracellular matrix deposition, angiogenesis, and cytokine production in polyether-polyurethane sponge implanted subcutaneously in male mice of these two strains. Although there was no difference in the gross appearance of the implants, further analysis of the wound healing responses, induced from 7 to 21 days post implantation, disclosed important differences between the New Zealand White and Balb/c strains. The intensity of inflammation (circulating tumor necrosis factor-alpha and inflammatory leukocytes levels) was lower but implant fibrosis (collagen and transforming growth factor-beta1) was higher in New Zealand White, compared with Balb/c mice. Angiogenesis (hemoglobin, vascular endothelial growth factor, and vascularity) in New Zealand White implants peaked earlier than in Balb/c mice. In conclusion, we have shown that wound healing responses are clearly different in this strain of lupus-prone mice and suggest that this pattern of repair was critically influenced by impaired inflammation and accelerated angiogenesis in the New Zealand White strain.
Assuntos
Modelos Animais de Doenças , Lúpus Eritematoso Sistêmico/fisiopatologia , Cicatrização/fisiologia , Animais , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Hemoglobinas/metabolismo , Interleucina-3/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes , Tampões de Gaze Cirúrgicos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Bronchoconstrictor responses were measured in lungs isolated from spontaneously hypertensive (SHR) and normotensive rats, perfused via the airways. Lungs from SHRs were more responsive than lungs from normotensive rats to methacholine, 5-hydroxytryptamine (5-HT), arachidonic acid or prostaglandin H(2). The responses of SHR airways to methacholine or 5-HT were unaffected by pretreatment in vivo with an inhibitor of nitric oxide (NO) synthase, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 30 mg kg(-1)), although responses in normotensive airways to methacholine, but not to 5-HT, were enhanced. Antigen challenge of isolated lungs from actively sensitized rats elicited bronchoconstriction, not different between strains. Pretreatment with L-NAME increased the response to antigen challenge only in normotensive lungs. Compound 48/80 induced bronchoconstriction in lungs from either strain, equally. These responses to compound 48/80 were unaffected by L-NAME pretreatment. Thus, SHR airways lack relaxing factors and degranulation of mast cells in SHR lungs was not affected by endogenous NO.
Assuntos
Broncoconstrição/fisiologia , Pulmão/fisiologia , Óxido Nítrico/fisiologia , Animais , Hiper-Reatividade Brônquica/fisiopatologia , Broncoconstritores/farmacologia , Degranulação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Hipersensibilidade/fisiopatologia , Técnicas In Vitro , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/fisiologia , Cloreto de Metacolina/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Ovalbumina/imunologia , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) and blocks prostaglandin (PG) biosynthesis associated with inflammatory conditions. In a model of peripherally induced inflammatory pain in rats, celecoxib, given systemically, induced a state of hypoalgesia where the nociceptive threshold was raised above basal values, an effect not observed after treatment with non-selective inhibitors of COX (indomethacin, piroxicam). Here, we have assessed the possibility that these atypical effects of celecoxib could be mediated by action at a site in the CNS. Inflammation and hyperalgesia were induced in one hind paw of rats by intraplantar injection of carrageenan (250microg). Nociceptive thresholds to mechanical stimulation were measured in the inflammed and contralateral paws for 6h after carrageenan injection. Celecoxib, SC236 (selective COX-2 inhibitors), indomethacin (non-selective COX inhibitor), SC560 (selective COX-1 inhibitor) or morphine were given by i.c.v. injection, 30 min before carrageenan. Celecoxib, SC236 or morphine-induced hypoalgesia whereas, after indomethacin or SC 560, the nociceptive threshold only returned to basal values. Naltrexone, also given i.c.v., reversed the hypoalgesia after celecoxib or morphine. Bestatin, an inhibitor of metabolism of endogenous opioid peptides, given i.c.v., potentiated the analgesic effects of a low dose of celecoxib. Taken together, these data indicate that celecoxib could act centrally after systemic administration to produce its characteristic profile of analgesia in this model of peripheral inflammatory pain. Moreover, this atypical analgesia appeared to be mediated by endogenous opioids rather than by inhibition of PG biosynthesis.