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1.
Neurochem Int ; 135: 104686, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31987865

RESUMO

Perinatal inflammation-induced reduction in pain threshold may alter pain sensitivity to hyperalgesia or allodynia which may persist into adulthood. In this study, we investigated the anti-inflammatory protective effect of interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory cytokine, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation and oxidative stress, thermal hyperalgesia, and mechanical allodynia in neonatal rats. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) or sterile saline was performed in postnatal day 5 (P5) rat pups, and IL-1ra (100 mg/kg) or saline was administered (i.p.) 5 min after LPS injection. Pain reflex behavior, spinal cord inflammation and oxidative stress were examined 24 h after LPS administration. Systemic LPS exposure led to a reduction of tactile threshold in the von Frey filament tests (mechanical allodynia) and pain response latency in the tail-flick test (thermal hyperalgesia) of P6 neonatal rats. Spinal cord inflammation was indicated by the increased numbers of activated glial cells including microglia (Iba1+) and astrocytes (GFAP+), and elevated levels of pro-inflammatory cytokine interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) 24 h after LPS treatment. LPS treatment induced spinal oxidative stress as evidenced by the increase in thiobarbituric acid reactive substances (TBARS) content in the spinal cord. LPS exposure also led to a significant increase in oligodendrocyte lineage population (Olig2+) and mature oligodendrocyte cells (APC+) in the neonatal rat spinal cord. IL-1ra treatment significantly reduced LPS-induced effects including hyperalgesia, allodynia, the increased number of activated microglia, astrocytes and oligodendrocytes, and elevated levels of IL-1ß, COX-2, PGE2, and lipid peroxidation (TBARS) in the neonatal rat spinal cord. These data suggest that IL-1ra provides a protective effect against the development of pain hypersensitivity, spinal cord inflammation and oxidative stress in the neonatal rats following LPS exposure, which may be associated with the blockade of LPS-induced pro-inflammatory cytokine IL-1ß.


Assuntos
Hiperalgesia/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Lipopolissacarídeos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Receptores de Interleucina-1/antagonistas & inibidores , Medula Espinal/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Feminino , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Masculino , Estresse Oxidativo/fisiologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-1/metabolismo , Medula Espinal/metabolismo
2.
Int J Mol Sci ; 19(10)2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30262747

RESUMO

In this study, we investigated the effects of minocycline, a putative suppressor of microglial activation, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation, allodynia, and hyperalgesia in neonatal rats. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) or sterile saline was performed in postnatal day 5 (P5) rat pups and minocycline (45 mg/kg) or vehicle (phosphate buffer saline; PBS) was administered (i.p.) 5 min after LPS injection. The von Frey filament and tail-flick tests were performed to determine mechanical allodynia (a painful sensation caused by innocuous stimuli, e.g., light touch) and thermal hyperalgesia (a condition of altered perception of temperature), respectively, and spinal cord inflammation was examined 24 h after the administration of drugs. Systemic LPS administration resulted in a reduction of tactile threshold in the von Frey filament tests and pain response latency in the tail-flick test of neonatal rats. The levels of microglia and astrocyte activation, pro-inflammatory cytokine interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the spinal cord of neonatal rats were increased 24 h after the administration of LPS. Treatment with minocycline significantly attenuated LPS-induced allodynia, hyperalgesia, the increase in spinal cord microglia, and astrocyte activation, and elevated levels of IL-1ß, COX-2, and PGE2 in neonatal rats. These results suggest that minocycline provides protection against neonatal systemic LPS exposure-induced enhanced pain sensitivity (allodynia and hyperalgesia), and that the protective effects may be associated with its ability to attenuate LPS-induced microglia activation, and the levels of IL-1ß, COX-2, and PGE2 in the spinal cord of neonatal rats.


Assuntos
Antibacterianos/uso terapêutico , Hiperalgesia/tratamento farmacológico , Minociclina/uso terapêutico , Animais , Antibacterianos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Feminino , Hiperalgesia/etiologia , Inflamação , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Minociclina/farmacologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia
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