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Modulation of nociceptive signalling on a spinal cord level under normal and pathological conditions
Pontearso, Monica
;
Špicarová, Diana
(advisor) ;
Uchytilová, Eva
(referee) ;
Krůšek, Jan
(referee)
Present pain therapies are often insufficient and poorly managed, mainly for neuropathic pain treatment. In the past years, research has provided a body of evidence on the association of nerve injury and inflammation with mobilized immune reactions. Many cytokines and hormones are released during injury or inflammation, and these factors regulate neuronal encoding of painful sensations. For example, in pre-clinical models, inflammatory cytokines cause or amplify nociception by enhancing neuron excitability. Besides increased excitability via direct neuronal sensitization, it has also been demonstrated that a reduction of synaptic inhibition (disinhibition) occurs naturally in the course of neuropathic and inflammatory pain states. The spinal cord dorsal horn (SCDH) is the first relay station of the ascending pain pathway and a crucial modulatory site of painful stimuli transmission. Three main aims characterize this doctoral thesis; each focused on the modulation of spinal nociceptive transmission by different molecules fundamental for pain processing. The first aim was to study the role of proinflammatory cytokine macrophage migration inhibitory factor (MIF) in nociceptive signalling following peripheral neuropathy induced by chronic constriction injury (CCI) of the sciatic nerve. The second aim...
Detailed record
The role of spinal TRPV1 receptors in nociceptive signalling and the modulatory effect of chemokine CCL2 and µ-opioid receptor agonists
Šulcová, Dominika
;
Paleček, Jiří
(advisor) ;
Krůšek, Jan
(referee)
The first nociceptive synapse in the spinal cord dorsal horn represents an important site, where nociceptive synaptic transmission can be modulated under pathological conditions. One of the modulatory mechanism involves activation of the transient receptor potential vanilloid 1 (TRPV1) that is expressed on central terminals of primary nociceptive neurons, where it regulates release of neurotransmitters and neuromodulators. Previous studies suggested that changes in TRPV1 activity may be related to effects of chemokine CCL2 (C-C motif ligand 2) and may be also involved in synaptic transmission modulation after µ-opioid receptors (MOP-R) activation. Because CCL2 receptors CCR2 often co-localize with TRPV1 and MOP-R, the goal of this work was to studypossible interactions of these receptors on the pre-synaptic endings of primaryafferents in the spinal cord dorsal horn and their role in nociceptive signalling under pathological conditions. The presented thesis focused on the effect of CCL2 during peripheral neuropathy and its interference with µ-opioid receptor activation. To studysynaptic transmission at the spinal cord level, patch-clamp recordings of excitatory post-synaptic currents (EPSC) in superficial spinal cord dorsal horn neurons in acute lumbar spinal cord slices from rats was used....
Detailed record
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