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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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Methods using preference in pain research
Komárková, Lucia ; Vaculín, Šimon (advisor) ; Mrózková, Petra (referee)
The thesis deals with neuropathic pain measurement in laboratory mice and rats. Neuropathic pain is characterized besides evoked allodynia and hyperalgesia also by spontaneous pain and anhedonia, further motivational-affective part of pain is highlighted. Traditional pain threshold testing is not appropriate method to measure these aspects of pain. Therefore, the aim of the thesis is to describe preference methods in pain research. We focused on three methods - conditioned place preference, sucrose preference test and thermal place preference. The first mentioned method creates an association between pain relief and a specific place, which afterwards the animal prefers. The conditioned place preference can be used to detect spontaneous pain. Sucrose preference test monitors decrease in consumption of sugar water after exposure to chronic pain, which can be interpreted as a sign of depression, so thanks to this method we have the opportunity to explore the interaction between pain and depression. The thermal place preference method studies changes of preferences between the cold and hot plate after induction of pain or analgesics. The findings based on preference methods help us to examine all aspects of neuropathic pain and develop more options for pain treatment.
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Physiological significance of pain
Zámostná, Kateřina ; Vaculín, Šimon (advisor) ; Telenský, Petr (referee)
Pain is defined as a physiological process associated with negative emotional experience which warns our body about impending damage. Apart from neuropathic pain, which by definition has no purpose, pain in effect provides a defensive function. However, this role is already being fulfilled by a different mechanism - the defensive reflex, which is evolutionarily older. Therefore we can ask, whether pain is only an emotional experience attached to this reflex, or if it has its own functions. To determine the physiological purpose of pain a rare syndrome of congenital analgesia, characterized by complete absence of pain, will be used. Based on a comparison of clinical cases of the syndrome with a population without pain disorders individual functions of pain will be described and connected to the individual components of pain - sensory- discriminatiory and affective-motivational. The sensory-discriminatory component provides a defensive, diagnostic and an informative function. The defensive function is analogous to the defensive reflex. The informative function transmits information about a physiological process, where pain plays a key role - labour. Diagnostic function applies in medicine and is based on verbal description of the defensive function. Functions of the SD component are involved at the time of...
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The role of ghrelin in modulation of neuropathic pain
Komárková, Lucia ; Vaculín, Šimon (advisor) ; Franěk, Miloslav (referee)
We are still unable to effectively suppress neuropathic pain, therefore it remains a serious problem. Ghrelin, the orexigenic hormone released by enteroendocrine stomach cells, could contribute to alleviation of the neuropathic pain by its antinociceptive effect. Previous studies have shown that ghrelin prevents development of nociceptive symptoms of neuropathic pain. The aim of our study was to determine whether chronic administration of ghrelin will affect the already fully developed neuropathic pain and differentiate its antinociceptive and analgesic effect. We used a model of chronic constriction injury of the sciatic nerve. We have proven that ghrelin suppressed the already developed thermal and mechanical hyperalgesia, so ghrelin not only prevents the development, but also suppresses the already developed nociceptive symptoms. However analgesia test showed that ghrelin did not affect the temperature preference, neither did induce the place preference. We suppose that ghrelin does not cause analgesia in neuropathic pain and its antinociceptive effect could be caused by anti- inflammatory or neuroprotective action. Key words: Ghrelin, neuropathic pain, chronic constriction injury, preference methods
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Comparison of reflex-based and operant methods when evaluating effects of treatment on pain in experimetnal models
Panušková, Kristýna ; Vaculín, Šimon (advisor) ; Šustková, Magdaléna (referee)
Pharmacological treatment of neuropathic pain is still insufficient. Methylphenidate, a psychostimulant that increases the dopamine and noradrenaline levels, is commonly used for treating ADHD. There have been reports of changes in patients pain thresholds by ADHD patients treated with methylphenidate. The aim of the study is to examine if methylphenidate can affect peripheral neuropathic pain. Neuropathic pain has been modelled on laboratory rats by chronic constriction of the ischiatic nerve. The effect of methylphenidate on the evoked pain component was evaluated on control animals and on animals with neuropathic pain using reflex (plantar test, vonFrey test) and operanting test (thermal place preference). The effect of methylphenidate on the spontaneous components of pain was evaluated using the methods of conditioned place preference. This study has proven that methylphenidate in an applicable dose of 1 mg/kg has an antialodynic effect but does not act antinociceptively. This study further confirms that methylphenidate in low doses does not act as attractant and has no effect on spontaneous pain. The last part of the study compares the different methods for pain measurement and comes to the conclusion that the plantar test is not an adequate method for evaluating the effect of analgesics...
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Psychoneuroimmunology of alexithymia
Uher, Tomáš ; Bob, Petr (advisor) ; Boleloucký, Zdeněk (referee) ; Smolík, Petr (referee)
Alexithymia represents a deficit in identifying and expressing emotions, paucity of fantasies, and an externally oriented cognitive style. Currently, numerous studies document that alexithymia and several mental and somatic disorders are significantly related. Several findings also indicate that this association might be caused by alexithymia related dysregulation of neuroendocrine and immune functions. Together these findings indicate that stressors related to alexithymia could underlie the process of neuroendocrine and immune dysregulation that likely may present a significant risk, sustaining and mediating pathogenesis of several disorders and particulary psychosomatic illnesses. In this context, it is also known that several proinflammatory cytokines may play a role in pain generation and that alexithymia is significantly associated with pain symptoms in several pain disorders. Following these findings this study includes several new data developing current state of the art and showing some alexithymia specific changes in patients with neurological disorders. Main finding of this study shows that alexithymia and anxiety in their specific interactions are linked to increased levels of interleukine-8 (IL-8) in cerebrospinal fluid (CSF) in the group of patients with non-inflammatory neurological...
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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 Possibilities of Influencing the Neuropathic Pain via Virtual Reality in Incomplete Spinal Cord Injury Patients.
Hunčovský, Tomáš ; Pánek, David (advisor) ; Pavlů, Dagmar (referee)
Title: The Possibilities of Influencing the Neuropathic Pain via Virtual Reality in Incomplete Spinal Cord Injury Patients. Objectives: The goal of this thesis is to determine how a long-term exposure to virtual reality affects experiencing neuropathic pain in the case of patients with incomplete spinal cord lesions. Methods: The study included 8 probands (3 females and 5 males) aged from 30 to 64 years (average age 49.5 ± 12.0 years) from among the clients of a charitable trust "Centrum Paraple". At the entrance examination, the participants received a pair of VR BOX VR-X2 virtual reality headsets enabling viewing of two-dimensional (2D) videos in the three-dimensional (3D) format. Thereafter they were watching, in their home environment, varied therapeutic videos depicting "virtual walking" - human walking viewed from a first person perspective. After 3 months of therapeutic intervention, a follow-up examination was carried out to determine the effect of the therapy. The Neuropathy Pain Scale and the International Spinal Cord Injury Pain Basic Data Set were used to assess changes in the perception of neuropathic pain. The results were statistically processed by means of a paired t-test in the R program. To monitor objective changes in the somatosensory and motor nervous systems, the evoked...
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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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