RESUMO
BACKGROUND: There is great comorbidity and similarity between chronic pain and major depressive disorders. We have recently shown that 10 days of social defeat stress (SDS) induces hyperalgesia regardless depressive-like behavior in mice. Here we aimed to investigate whether social stress predisposes to chronic pain and, inversely, whether chronic pain predisposes to stress-induced depression. METHODS: Firstly, we used the 10 days SDS paradigm in mice followed by a mild protocol of repetitive inflammatory stimulus to evaluate if SDS would predispose to persistent hyperalgesia development. Secondly, we used the intense protocol of repetitive inflammatory stimulus followed by a subthreshold SDS to evaluate if persistent hyperalgesia would predispose to depressive-like behavior of social avoidance. RESULTS: Our results showed that SDS predispose to chronic pain, since stressed mice injected with PGE2 for 7 days (mild protocol), stimuli normally not sufficient to trigger chronic pain, showed persistent hyperalgesia. Also, we showed that persistent hyperalgesia induced by repetitive inflammatory stimuli predispose to long-lasting depressive-like behavior of social avoidance induced by subthreshold SDS. LIMITATIONS: We did not analyze molecular mechanism associated with chronic pain and depressive-like behavior induced by SDS. However, we hypothesized that SDS and 14 days of PGE2 would generate neuroplasticity on brain areas shared by chronic pain and depression, predisposing to pain chronification and depressive-like behavior, respectively. CONCLUSIONS: We can conclude social stress as a key and a common factor for chronic pain and depression. We can also conclude that SDS predisposes to chronic pain and, inversely, chronic pain predisposes to depressive-like behavior.
Assuntos
Dor Crônica , Transtorno Depressivo Maior , Animais , Dor Crônica/epidemiologia , Comorbidade , Depressão/epidemiologia , Modelos Animais de Doenças , Hiperalgesia/epidemiologia , Camundongos , Camundongos Endogâmicos C57BL , Comportamento Social , Estresse Psicológico/complicações , Estresse Psicológico/epidemiologiaRESUMO
Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.
Assuntos
Dor Crônica/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Condicionamento Físico Animal/fisiologia , Derrota Social , Estresse Psicológico/fisiopatologia , Animais , Comportamento Animal , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacosRESUMO
BACKGROUND: ß-Blockers reduce temporomandibular joint (TMJ) pain. We asked whether they also reduce TMJ inflammation and, if so, whether this anti-inflammatory effect contributes to its analgesic action. METHODS: We measured many parameters of the inflammatory response after co-administration of the ß-blocker propranolol with the inflammatory agent carrageenan in the TMJ of female rats. We also hypothesized that the activation of ß-adrenoceptors in the TMJ induces nociception mediated, at least in part, by the inflammatory response. To test this hypothesis, we examined the nociceptive response induced by the activation of the ß-adrenoceptors in the TMJ in female rats pretreated with thalidomide and fucoidan. RESULTS: We found that the co-administration of propranolol with carrageenan in the TMJ of female rats significantly reduced several parameters of the inflammatory response induced by carrageenan such as plasma extravasation, neutrophil migration and the release of the pro-inflammatory cytokines TNF-α, IL-1ß and CINC-1. Furthermore, the injection of the ß-adrenergic receptor agonist isoproterenol in the TMJ induced nociception that was significantly reduced by thalidomide, fucoidan and by the co-administration of propranolol but not of the α-adrenergic receptor antagonist phentolamine. CONCLUSIONS: Propranolol has anti-inflammatory effects that contribute to its antinociceptive action in the TMJ of females. SIGNIFICANCE: ß-Blockers have an anti-inflammatory effect on temporomandibular joint (TMJ) that contributes to its analgesic effect. The results of this work suggest that ß-blockers can be used to treat the painful conditions of TMJ, especially when they are associated with an inflammatory process.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Nociceptividade/efeitos dos fármacos , Propranolol/farmacologia , Articulação Temporomandibular/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/farmacologia , Carragenina/farmacologia , Quimiocina CXCL1/efeitos dos fármacos , Quimiocina CXCL1/imunologia , Feminino , Imunossupressores/farmacologia , Interleucina-1beta/efeitos dos fármacos , Interleucina-1beta/imunologia , Dor/tratamento farmacológico , Medição da Dor/efeitos dos fármacos , Fentolamina/farmacologia , Polissacarídeos/farmacologia , Ratos , Ratos Wistar , Articulação Temporomandibular/imunologia , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Talidomida/farmacologiaRESUMO
Clinical studies show an evident antidepressive effect of physical exercise and animal research corroborate such evidence. However, the neurobiological mechanisms underlying the antidepressive effect of exercise are not completely understood. Notwithstanding, it is known that exercise increases brain-derived neurotrophic factor (BDNF) expression in the hippocampus similarly to antidepressant drugs. BDNF is synthesized as a precursor molecule that undergoes a proteolytic cleavage to generate either a mature or a truncated isoform. Precursor and mature BDNF are assumed to elicit opposing biological effects in neuroplasticity. In the present study we investigated the effect of voluntary physical activity on precursor and mature brain-derived neurotrophic factor levels and on proBDNF cleavage related genes, p11 and tissue plasminogen activator (tPA), as well as the antidepressive and cognitive effects of voluntary physical activity. Mice had access to mobile or locked running wheels for 28 days and were submitted to forced-swim, tail suspension and water maze tests. Their hippocampi were dissected and analyzed by Western blot and real time RT-PCR. Voluntary physical activity, but not locked wheel exposure, induced a robust increase in hippocampal mature BDNF protein levels, as well as in p11 and tPA mRNA expression; and also promoted antidepressive effects and improved learning, when compared with sedentary mice. On the other hand, there were no significant differences between any groups in the expression of precursor or truncated isoforms of BDNF. Our data suggest that the antidepressive effect of the physical exercise may depend, at least in part, on changes in BDNF post-translational processing.
Assuntos
Anexina A2/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Condicionamento Físico Animal/fisiologia , Proteínas S100/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Animais , Anexina A2/genética , Western Blotting , Depressão/metabolismo , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Processamento de Proteína Pós-Traducional , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas S100/genética , Ativador de Plasminogênio Tecidual/genéticaRESUMO
The military dermatologist has a specific and significant role in military operations--in time of war as well as in peace. Many dermatologists are unfamiliar with the impact that our specialty and cutaneous disease has upon the ability of the military to fulfill the missions, duties, and responsibilities assigned by our government. This article highlights a few of the recent or ongoing types of military operations in which our specialty plays a prominent part.