RESUMO
Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and central nervous systems in this phenomenon remain unclear. To clarify this, we induced hyperalgesia in rats using Bjv and collected tissues from dorsal root ganglia (DRGs) and spinal cord (SC) at 2 and 4 h post-induction. Samples were labeled for Iba-1 (macrophage and microglia), GFAP (satellite cells and astrocytes), EGR1 (neurons), and NK1 receptors. Additionally, we investigated the impact of minocycline, an inhibitor of microglia, and GR82334 antagonist on Bjv-induced hyperalgesia. Our findings reveal an increase in Iba1 in DRG at 2 h and EGR1 at 4 h. In the SC, markers for microglia, astrocytes, neurons, and NK1 receptors exhibited increased expression after 2 h, with EGR1 continuing to rise at 4 h. Minocycline and GR82334 inhibited venom-induced hyperalgesia, highlighting the crucial roles of microglia and NK1 receptors in this phenomenon. Our results suggest that the hyperalgesic effects of Bjv involve the participation of microglial and astrocytic cells, in addition to the activation of NK1 receptors.
Assuntos
Bothrops , Venenos de Crotalídeos , Gânglios Espinais , Hiperalgesia , Receptores da Neurocinina-1 , Animais , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Venenos de Crotalídeos/toxicidade , Masculino , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Receptores da Neurocinina-1/metabolismo , Minociclina/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/genética , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Ratos , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Proteínas dos Microfilamentos/metabolismo , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Ratos Sprague-DawleyRESUMO
Changes in 5-HT1A receptor (5-HT1AR)-mediated neurotransmission in the hippocampus have been associated with anxiety, depression and in the mode of action of antidepressant drugs. It has been commonly accepted that whereas the dorsal pole of the hippocampus (DH) is involved in cognitive processing, the ventral pole (VH) is associated with emotional regulation. However, to date, only a few studies have directly addressed the role played by VH 5-HT1ARs in anxiety and panic processing, and their results are conflicting. Here we report that intra-VH administration of the 5-HT1A receptor agonist 8-OH-DPAT, the endogenous agonist serotonin (5-HT), or the standard anxiolytic benzodiazepine midazolam impaired the acquisition of inhibitory avoidance in the elevated T-maze (ETM) of male Wistar rats, indicating an anxiolytic effect. Conversely, local injection of the 5-HT1AR antagonist WAY-100635 caused the opposite effect. These results were equally found in the Vogel conflict test. None of these drugs interfered with locomotor activity in the open-field test, nor did they alter the expression of the escape response in the ETM, a defensive behavior associated with panic. Pre-injection of a sub-effective dose of WAY-100635 in the VH blocked the anxiolytic effect of 5-HT or 8-OH-DPAT in the Vogel test, confirming the involvement of 5-HT1AR for this behavioral effect. The effect in this test was anxiety-selective as none of the drugs affected water consumption or nociception. In conclusion, our results suggest that 5-HT1ARs in the VH play a tonic inhibitory role in anxiety processing. These receptors, however, are not involved in the regulation of panic-related escape behavior.