|
|
The role of regulatory protein SGIP1 in nociceptive synaptic transmission at the spinal cord level.
Mužík, David ; Špicarová, Diana (advisor) ; Lindovský, Jiří (referee)
Cannabinoid receptor 1 (CB1), abundantly expressed in the CNS, is a promising target for the pharmacological treatment of pathological pain conditions due to its function as an inhibitor of neurotransmitter release from presynaptic neurons. Recently, the SGIP1 protein has been found to interact with the CB1 receptor and participates in the modulation of nociception. However, whether SGIP1 modulates spinal CB1 receptor signaling at the spinal cord level is unknown. To answer this question, we used the patch-clamp method in the superficial spinal cord dorsal horn neurons of wild-type (WT) and knockout (KO) SGIP1 mice to measure spontaneous (s) and miniature (m) excitatory postsynaptic currents (EPSCs). Results of naive mice and mice with carrageenan-induced peripheral inflammation were compared. The results show that the efficacy of the CB1 receptor agonist WIN 55,212-2 at the first spinal nociceptive synapse is identical in naive mice for both SGIP1 WT and KO phenotypes. The control frequencies of both groups of neurons did not differ in naïve conditions or the peripheral inflammation model. On the contrary, the WIN 55,212-2 application was more effective in SGIP1 KO mice during peripheral inflammation. This study further addressed how CB1 receptor activation affects spinal inhibitory synaptic...
|
|
|
The role of cannabinoid receptor 1 in the modulation of nociceptive signaling at spinal cord level
Dresslerová, Denisa ; Špicarová, Diana (advisor) ; Kořínek, Miloslav (referee)
Pain is an integral part of our lives, it warns of possible impending tissue damage and represents a form of protection for the body. Pain can become directly harmful if it persists. It is perceived individually in different intensity, place and length. In most cases, it is a very unpleasant and robust emotional experience. Before pain perception, nociceptive signalling occurs. When a harmful stimulus is detected in peripheral tissues, free nerve endings are activated, the plasma membrane is depolarized and generated action potential convoys to information about the presence of a nociceptive stimulus to the dorsal horn of the spinal cord. The process of nociception includes stimulation of nerve endings, transduction, signal transmission by nerve fibers into the spinal cord, synaptic transmission and conducting an action potential to the brain, where nociceptive signaling is evaluated. An important area for nociceptive modulation is the dorsal horn of the spinal cord, where synaptic transmission occurs between primary and secondary nociceptive neurons. The individual components of the endocannabinoid system play a significant role in the modulation of synaptic transmission. The major cannabinoid receptors are cannabinoid receptors 1 (CB1) and 2 (CB2), and many endocannabinoids also activate...
|
|
| |
|
|
Effect of aging, season and temperature on pain threshold in laboratory rat
Vítková, Jana ; Vaculín, Šimon (advisor) ; Špicarová, Diana (referee)
Every living creature meets with pain up to these days. Many researches are made in labour conditions, we try to find out how the pain works and how we can suppress it or how we can utilize it in our welfare. Our work is focused on the effect of aging, season, acclimatization and ambient temperature on thermal and mechanic pain threshold in laboratory rats. We were interested how these factors affect the results of the research. Adult male Wistar rats were used in all experiments. Thermal pain thresholds were measured by withdrawal reaction of three body sites: forelimbs, hind limbs and tail. Mechanic pain thresholds were measured by von Frey filaments and a skin temperature was measured by IR thermometer, both of three body sites. Our results demonstrate that : (i) aging have effect on nociceptive pain threshold; (ii) there is presence of cranio-caudal distribution of nociceptive sensitivity in aging and in changing of ambient temperature - forelimbs have lower latency than hind limbs; (iii) thermal pain threshold depends indirectly on ambient and skin temperature; (iv) there was no effect of repeated measurement on nociceptive thresholds of the three body sites; (v) hind limbs and tails are more sensitive to changes of ambient temperature than forepaws; (vi) mechanic pain threshold not change...
|
|
|
Modulation of spinal nociceptive mechanisms under pathological conditions
Mužík, David ; Špicarová, Diana (advisor) ; Smejkalová, Terézia (referee)
Pain is a crucial component of the body's innate defenses, which helps us to respond to the damage that is threatening or imminent. If the pain persists even after the injury has healed, or arises for no apparent reason, it itself becomes harmful. Nociception begins with the detection of a noxious stimulus that irritates free nerve endings on the peripheral projections of spinal ganglion neurons. If the stimulus induces depolarization of the cell and an action potential forms, information of the stimulus is conducted by thinly myelinated Aδ fibers, or unmyelinated C fibers to the spinal cord dorsal horn. Here, the first synapses of sensory pathways are located, which allow the transmission of nociception to secondary afferent neurons, and these further direct the information to the higher centers of the CNS. Synapses in the dorsal horn are key to modulating nociceptive signaling, in which the endocannabinoid system, including endogenous cannabinoids and their receptors, plays a significant role. However, under pathological conditions such as the development of neuropathic pain or neuroinflammation, changes in the expression and function of agonists and receptors of the endocannabinoid system occur. These changes are of great importance in the onset and persistence of pathological pain. The study of...
|
|
|
Pathophysiology of Spinal Cord Injury Studied by In Vivo Optical Imaging
Vančíková, Sabína ; Valášková, Barbora (advisor) ; Špicarová, Diana (referee)
Patients suffering from spinal cord injury experience physical, social, and vocational impairment. It is a condition often causing a permanent disability mainly due to axonal regeneration incapability in the central nervous system. The primary insult simultaneously damages cells in the lesion site and initiates a cascade of secondary cellular, vascular, and biochemical events extending the injury. These pathophysiological mechanisms are examined using multiple approaches. Novel imaging techniques complement classical histopathological methods and neuroanatomical tracing. Recent studies employ transgenic mice and two-photon microscopy to observe single cells in the injury site and the nearby vasculature in vivo longitudinally. In vivo optical imaging enables studying of axonal responses, such as degeneration, regeneration, and neurovascular interactions. It also gives an opportunity to assess the effects of applied drugs directly. New findings lead to a better understanding of the pathophysiology of spinal cord injury, resulting in the ability to develop other therapeutic strategies improving the outcome after injury. Keywords: spinal cord injury, pathophysiological mechanisms, axonal regeneration, Wallerian degeneration, animal models, transgenic mice, in vivo imaging, two-photon excitation microscopy
|
|
| |
|
|
Effect of aging, season and temperature on pain threshold in laboratory rat
Vítková, Jana ; Vaculín, Šimon (advisor) ; Špicarová, Diana (referee)
Every living creature meets with pain up to these days. Many researches are made in labour conditions, we try to find out how the pain works and how we can suppress it or how we can utilize it in our welfare. Our work is focused on the effect of aging, season, acclimatization and ambient temperature on thermal and mechanic pain threshold in laboratory rats. We were interested how these factors affect the results of the research. Adult male Wistar rats were used in all experiments. Thermal pain thresholds were measured by withdrawal reaction of three body sites: forelimbs, hind limbs and tail. Mechanic pain thresholds were measured by von Frey filaments and a skin temperature was measured by IR thermometer, both of three body sites. Our results demonstrate that : (i) aging have effect on nociceptive pain threshold; (ii) there is presence of cranio-caudal distribution of nociceptive sensitivity in aging and in changing of ambient temperature - forelimbs have lower latency than hind limbs; (iii) thermal pain threshold depends indirectly on ambient and skin temperature; (iv) there was no effect of repeated measurement on nociceptive thresholds of the three body sites; (v) hind limbs and tails are more sensitive to changes of ambient temperature than forepaws; (vi) mechanic pain threshold not change...
|
|
| |
|
|
Modulation of nociceptive synaptic transmission in the spinal cord dorsal horn
Špicarová, Diana ; Paleček, Jiří (advisor) ; Vlachová, Viktorie (referee) ; Rokyta, Richard (referee)
7 ABSTRACT Pathological pain states linked to several diseases or tissue damage are often associated with increased sensitivity to stimuli. The main underlying mechanisms of this hypersensitivity are peripheral sensitization of nociceptors and central sensitization in the spinal cord. One of the crucial processes of central sensitization is the modulation of synaptic transmission at the dorsal horn of the spinal cord. Studies included in my doctoral thesis investigate the possibilities of regulation of synaptic strength by cytokine TNFα, insulin and TRPV1 receptors agonist N-oleoyldopamine (OLDA). These three compounds are synthesized in the CNS, while TNFα is produced in the spinal cord notably during neuropathy. TNFα and insulin have a potential to modulate synaptic transmission. Endogenous TRPV1 receptors agonist OLDA can activate spinal TRPV1 receptors, which are highly expressed on central endings of nociceptive dorsal root ganglion (DRG) neurons. TRPV1 receptors are known as integrators of nociceptive stimuli particularly from the studies of peripheral receptors on nociceptors, which could be sensitized by inflammatory mediators and activated by temperature increase or decrease pH that is unlike in the spinal cord. In our experiments miniature excitatory postsynaptic currents (mEPSCs) or evoked EPSCs...
|
guest ::
