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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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Ongoing pain in animal models of neuropathic pain
Priessnerová, Denisa ; Vaculín, Šimon (advisor) ; Honc, Ondřej (referee)
Although spontaneous pain is a global problem, there is still no effective treatment. Constructive research started only 40 years ago. Research based on pain mechanisms and potential treatment has been done on animal models of neuropathic pain. This thesis is focused on animal models, which could be either induced by chronic constriction of the sciatic nerve (CCI) or spinal nerve ligation (SNL). Both models should induce spontaneous, ongoing pain along with evoked pain (allodynia and hyperalgesia). Tests, made on these models, are based on detection and measurement of spontaneous pain, while not using an external stimulus. The outcome of the tests is not always effective. Most of the time, they do not evince signs of spontaneous pain. These tests are also less effective and fewer in numbers compared to those using external stimulus. The goal of this thesis was to analyze all the research including spontaneous and ongoing pain in CCI and SNL models. It was important to focus on certain methods that do not use external stimulus during testing. PubMed database was used for searching articles. The most common words searched were "spontaneous" and "ongoing". Found articles were evaluated and searched for methods indicating and measuring spontaneous pain without an external stimulus. Most of the methods...
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Reflexive measurement of thermal hyperalgesia in neuropathic pain model
Panušková, Kristýna ; Vaculín, Šimon (advisor) ; Adámek, Pavel (referee)
Neuropathic pain substantially decreases a person's quality of life and thus far nothing has been invented that can alleviate that pain. One of the most commonly used model for induced peripheral neuropathic pain in animals is chronic constriction of the sciatic nerve. Experimental induction of neuropathic pain in rats is verified by reflexive measurement. Reflexive measuring can also be used to test the efficacy of the experimental treatment. The large range of reflexive tests that can be applied differ in terms of the stimulus used and the area of stimulation. This bachelor thesis will focus on analyses of the thermal pain threshold after a chronic constriction injury (CCI) to the sciatic nerve. Articles used in this thesis were found in the electronic database PUBMED/MEDLINE by searching for the terms "chronic constriction injury" and "pain threshold" for last 10 years. Articles related to the thermal pain threshold of rats after CCI were ranked according to the prestige of magazine that published them and ten articles with a quartile of 1 were selected for further analyses. The tests used, control methods during the study, measuring interval, measurement before operation and pain threshold values were extracted from these articles. Measurement of behavioral signs is not unified. The Hargreaves...
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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 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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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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Evaluation of short-term effect of Extracorporeal shockwave therapy into muscular trriger points.
Novák, Jan ; Čech, Zdeněk (advisor) ; Vaculín, Šimon (referee)
Diplomová práce Hodnocení krátkodobého efektu aplikace rázové vlny na MTrP Abstract This thesis concerns the application of radial extracorporeal shockwave therapy into muscular trigger points. It's location is derived from the descending part of trapezius muscle on the side of the dominant upper extremity. The performance analysis is based on using partially double-blind placebo-controlled, randomized clinical trial. The effects of the therapy were investigated in 28 subjects divided into experimental and control groups and objectively manifested by measuring the pressure pain threshold. Furthermore, the measuring of the active range of motion of the cervical spine, and the measuring of the maximal voluntary wrist and third finger flexion (measured before and after the therapy). After the therapy, the pressure pain threshold value of the trigger point located in trapezius muscle increased on average from 199 to 295 kPa (p = 0,025). The cervical spine lateral flexion increased on average by 3 degrees towards to the side of non-dominant upper extremity (p = 0,045). This study also investigates the pressure pain threshold value changes of 7 reference points placed remotely from the area of the application. After the shockwave therapy, the pressure pain threshold values of these reference points increased on...
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Use of adrenergic receptor alpha2-agonists in pain treatment
Soláriková, Ivana ; Vaculín, Šimon (advisor) ; Maršáková, Lenka (referee)
α2-adrenergic receptor agonists are adjuvant analgesics involved in the modulation and treatment of pain acting in the noradrenergic system. Binding of α2 agonists to receptors initiates a cascade of actions leading i.a. to antinociception. The most clinically applied analgesics of this type include clonidine, dexmedetomidine, and xylazine used in veterinary medicine. The ability to potentiate the effects of opioid and nonopioid analgesics and anesthetics leading to dose reduction is especially advantageous as it relieves unpleasant side effects associated with opioid use, and reduces the risk of tolerance development. They are effective in local anesthesia due to the peripheral site of action and do not cause characteristic, centrally mediated side effects of hemodynamic character. They are involved in the suppression of inflammatory response in the body by inhibiting the production of proinflammatory cytokines. Despite the wide range of action, α2 agonists appear to be safe in many different contraindications, such as sepsis, diabetes or pregnancy. Keywords: α2-adrenergic receptors, agonists, pain, analgesia, clonidine, dexmedetomidine, potentiation, adjuvant
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Behavioral expression of pain in rats
Zámečník, Jakub ; Vaculín, Šimon (advisor) ; Boukalová, Štěpána (referee)
The aim of this work is to summarize the current knowledge regarding the behavioral expressions of pain in rat. The work is focused on rats, because they are one of the most used laboratory animals, and may experience pain in some experiments. Behavioral expressions of pain were selected, because they are quite easily recognizable and measurable. The reader will be first acquainted with the necessary basics associated with the phenomenon of pain, with its conception in animals, with classification, physiology and for example with the ways in which are in rats experimentally induced pain. Then in the second part, there are shown individual behavioral expressions with examples in which cases were these manifestations observed. So everyone who is interested can learn something about pain in connection with the avoidance reaction, pose, appearance, specific movements of rat, vocalization, changes in eating and drinking, changes in activity, anxiety, cognitive functions and many other expressions. The work can be valuable contribution for all workers with animals and with its character can contribute to animal welfare. Powered by TCPDF (www.tcpdf.org)
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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...
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