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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel ; Paleček, Jiří (advisor) ; Vaculín, Šimon (referee) ; Vlachová, Viktorie (referee)
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel ; Paleček, Jiří (advisor) ; Vaculín, Šimon (referee) ; Vlachová, Viktorie (referee)
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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Dysregulation of the endocannabinoid system in obesity and its modulation by dietary omega-3 fatty acids
Kalendová, Veronika ; Rossmeisl, Martin (advisor) ; Hlaváčková, Markéta (referee)
Obesity is associated with metabolic complications including insulin resistance, dyslipidemia and hypertension (metabolic syndrome). The endocannabinoid system (ECS) activity is elevated in obesity, which can further potentiate metabolic impairments. Pharmacological treatment based on the cannabinoid receptor CB1 blockade led to a decrease in body weight and significant improvements of metabolic parameters in obese individuals. However, parallel effects on the central nervous system resulted in unwanted side-effects including anxiety and depressive moods. Recent experimental studies suggested that dietary interventions with omega-3 polyunsaturated fatty acids of marine origin (EPA, DHA) can decrease the ECS activity in peripheral tissues (adipose, liver, pancreas), and thus partially protect against metabolic disturbances in obesity. One of the underlying mechanisms behind the effects of EPA and DHA could be a replacement of arachidonic acid from the sn-2 position of membrane phospholipids, thereby reducing the substrate availability for the synthesis of endocannabinoid molecules. Key words: omega-3 fatty acids, obesity, endocannabinoid system, 2-arachidonoylglycerol, anandamide
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Cannabinoid signalling and its physiological significance
Pavluch, Vojtěch ; Novotný, Jiří (advisor) ; Moravcová, Simona (referee)
Lidská společnost je ve styku s kanabinoidními látkami již od starověku. Ať už lidé využívali rostlinnou biomasu nebo bylinné léčitelství, bylo konopí vždy předmětem diskuzí. Poznatky objasňující molekulární principy účinku látek obsažených přírodně jen v konopí jsou však známy jen několik málo desítek let. Cílem této práce je charakterizovat subtypy receptorů, na které se kanabinoidy vážou, molekulární mechanismy jejich působení, následné konsekvence ve fyziologii a také poukázat na potenciální uplatnění jak rostlinných, tak syntetických kanabinoidů v lékařství. Kanabinoidní receptory jsou hojně se vyskytující podskupinou integrálních membránových receptorů, spadající do velké rodiny receptorů spřažených s G-proteiny. Vzhledem k ubikviternímu výskytu v organismu tyto receptory po aktivaci příslušnými lipofilními ligandy ovlivňují celou škálu fyziologických pochodů. Vazba kanabinoidních látek na daný subtyp těchto receptorů spouští specifickou signální kaskádu v buňce a ovlivňuje tak určitým způsobem buněčný metabolismus. Studium kanabinoidních receptorů a jejich ligandů přispívá k porozumění procesům zahrnujícím tvorbu paměti a učení, ale také mechanismům zapojeným v analgézii, imunomodulaci a buněčné proliferaci. Tyto receptory však ovlivňují také fyziologii kardiovaskulárního systému nebo...
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