Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of nigrostriatal dopaminergic neurons, and most patients report pain, in many cases early motor and cognitive dysfunction characteristic of the disease. Experimentally, it was observed reduction of nociceptive threshold in parkinsonian rats in different models of nociception, but the mechanisms involved have not yet been clarified. Previously, we observed that striatal dopaminergic lesion induces bilateral mechanical hyperalgesia in rats, which is accompanied by the loss of serotonergic neurons in the nucleus raphe magnus (NMR) and of noradrenergic neurons in the locus coeruleus (LC). Knowing that neuroinflammation, including glial activation, affects different structures in experimental PD, the aim of this project is to investigate the pattern of neuronal and glial activation in the NMR and LC nuclei, involved in the modulation of nociceptive response after unilateral striatal injection of the neurotoxin 6-OHDA. For that, we will evaluate the mechanical nociceptive response by the paw pressure test. To characterize the nigrostriatal injury, the animals will be evaluated by the apomorphine-induced rotational asymmetric test and by the loss of dopaminergic neurons by in the substantia nigra. The pattern of glial activation in the NMR and LC, after striatal injury, will be determined by immunostaining for GFAP (astrocytic marker) and Iba-1 (microglial marker). Also, it will be evaluated by immunoblotting, in these same nuclei, the expression pattern of IL-² and TNF-± hyperalgesic proinflammatory cytokines and purinergic receptor P2X4 (marker of activated microglia). In an attempt to correlate neuronal death with neuronal and/or glial activation we will perform double staining by immunofluorescence for TUNEL and/or c-Fos, GFAP and Iba-1. With this project we intend to deepen the understanding of the effect of nigrostriatal lesion on serotonergic and noradrenergic nuclei of descending analgesic pathway and the role of glial cells in this response.
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