RESUMO
Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.
Assuntos
Dor Aguda/metabolismo , Dor Crônica/metabolismo , Membro Posterior/irrigação sanguínea , Nociceptividade , Distrofia Simpática Reflexa/metabolismo , Canais de Cátion TRPC/antagonistas & inibidores , Acetilglucosaminidase/metabolismo , Dor Aguda/etiologia , Aldeídos/metabolismo , Animais , Dor Crônica/etiologia , Temperatura Baixa , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Ácido Láctico/sangue , Masculino , Estresse Oxidativo , Peroxidase/metabolismo , Carbonilação Proteica , Ratos , Ratos Wistar , Distrofia Simpática Reflexa/etiologia , Traumatismo por Reperfusão/complicações , Albumina Sérica/metabolismo , Canal de Cátion TRPA1 , Canais de Cátion TRPC/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
Proteins are important targets of several modifications caused by oxidative stress, leading to structural changes and consequently partial or total loss of their functions. The oxidized proteins include advanced oxidation protein products (AOPP) derived from oxidation-modified albumin, as well as fibrinogen and lipoproteins. An increase in AOPP levels indicates an oxidative stress state and the presence of coexisting inflammation. Several investigations have also suggested an association between high AOPP levels and aging-related diseases. However, the link between elevated AOPP levels and elderly mortality risk has not yet been investigated. Here, we report on a 5-year longitudinal study that investigated the potential association between AOPP levels and mortality using a population-based representative sample of riparian elders living in Brazilian Amazon region (Maués-AM). Age, sex, socioeconomic and cultural conditions, chronic morbidities, polypharmacy, and previous morbidities were also tested as potential confounders. The AOPP levels were measured in 540 (84.78%) individuals, all of whom were followed over a 5-year period in order to establish the mortality rate. Within this study period, 74 (13.7%) elders died and 466 (86.3%) survived. The AOPP levels were higher among the elders who died within the 5-year period (46.27 ± 40.6 mmol/L) compared with those who survived (36.79 ± 20.84 mmol/L) (p = 0.002). The analysis confirmed the link between high AOPP levels and mortality risk, independent of other intervenient factors. These results suggest that elevated AOPP levels could be used to predict mortality risk in elderly patients.