الفهرس 
Parkinson’s DiseaseOnly 14 pages are availabe for public view
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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
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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
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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.