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Abstract Pain is the major non-motor symptom in Parkinson’s disease (PD). Its mechanism is still poorly understood although an increase in excitation or a decrease in inhibition have been reported in preclinical studies. These studies have mostly investigated mechanical pain by considering the decrease in a nociceptive threshold. Only a few studies have focused on thermal pain in animal models of PD. Besides, fluorescence tracers have been widely used to label projecting neurons, but the linkage between the susbtantia nigra and the spinal pain process hasn’t yet been demonstrated thoroughly. Therefore, the goal of this study was to assess the thermal nociceptive behavior of rats subjected to 6- hydroxydopamine (6-OHDA) administration, which constitutes an animal model of PD. Also, to investigate inhibitory and excitatory markers in the 6- hydroxydopamine (6-OHDA) PD rat model. Therefore, the expression of three inhibitory markers parvalbumin, glutamate decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) was evaluated in bilateral 6-OHDA lesioned rat. Besides, GFAP, Serine Racemase and Pannexins were studied. In addition, Fluororuby (FR) has been injected in the substantia nigra pars compacta to assess its anterograde projections to discover whether it has dopaminergic projections to the spinal cord or not. Our results demonstrated significant thermal sensitivity to cold temperatures of 10 °C and 15 °C, and not to Summary 272 higher temperatures, in 6-OHDA-lesioned rats when compared with sham. 6-OHDA-lesioned rats also showed cold allodynia as demonstrated by a significant difference in the number of flinches, latency and reaction time to acetone stimulus. Ropinirole administration, a dopamine receptor 2 (D2R) agonist, blocked the acetone-induced cold allodynia in 6- OHDA-lesioned rats. In addition, mechanical hypersensitivity and static allodynia, as demonstrated by a significant difference in the vocalization threshold and pain score respectively, were noticed in 6-OHDA-lesioned rats. Acetone stimulus induced a significant increase in extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) phosphorylation, a pain process molecular marker, in the spinal dorsal horn (SDH), the insular and cingulate cortices, besides the increase of CFOS excitatory pain marker, in 6-OHDA-lesioned rats when compared to sham. There was a significant increase in the expression of the three inhibitory markers parvalbumin, GAD67 and VGAT of 6- OHDA lesioned rats. In parallel, there was also an increase of the excitatory marker protein kinase C gamma (PKCγ). PKCγ cells have a crucial role in pain chronicity and are regulated by GABAergic influences. This highlighted an increase in excitation and a decrease in inhibition in the SDH. In addition, GFAP and Serine Racemase levels were increased in sham animals more than 6-OHDA lesioned ones, while Pannexin-2 Summary 273 was increased in 6-OHDA lesioned rats more than sham animals. After tracing the FR coupled with dopaminergic Tyrosine hydroxylase marker, some brain stem structures received the tracer having dopaminergic origin, nevertheless, the spinal cord lacked dopaminergic projections from the SNpc. |