Indiana University-Purdue University Indianapolis (IUPUI) / Voltage-gated sodium channels (VGSCs) are transmembrane proteins responsible for the initiation of action potentials in excitable tissues by selectively allowing Na+ to flow through the cell membrane. VGSC subtype Nav1.7 is highly expressed in nociceptive (pain-sensing) neurons. It has recently been shown that individuals lacking the Nav1.7 subtype do not experience pain but otherwise function normally. In addition, dysfunction of Nav1.7 caused by point mutations in the channel is involved in two inherited pain disorders, primary erythromelalgia (PE) and paroxysmal extreme pain disorder (PEPD). This indicates Nav1.7 is a very important component in nociception. The aims of this dissertation were to 1) investigate if the antipsychotic drug, trifluoperazine (TFP), could modulate Nav1.7 current; 2) examine changes in Nav1.7 properties produced by the PE mutation N395K including sensitivity to the local anesthetic (LA), lidocaine; and 3) determine how different inactivated conformations of Nav1.7 affect lidocaine inhibition on the channel using PEPD mutations (I1461T and T1464I) that alter transitions between the different inactivated configurations of Nav1.7. Standard whole-cell electrophysiology was used to determine electrophysiological and pharmacological changes in WT and mutant sodium currents. Results from this dissertation demonstrate 1) TFP inhibits Nav1.7 channels through the LA interaction site; 2) the N395K mutation alters electrophysiological properties of Nav1.7 and decreases channel sensitivity to the local anesthetic lidocaine; and 3) lidocaine stabilizes Nav1.7 in a configuration that decreases transition to the slow inactivated state of the channel. Overall, this dissertation answers important questions regarding the pharmacology of Nav1.7 and provides insight into the changes in Nav1.7 channel properties caused by point mutations that may contribute to abnormal pain sensations. The results of this dissertation on the function and pharmacology of the Nav1.7 channel are crucial to the understanding of pain pathophysiology and will provide insight for the advancement of pain management therapies.

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Isaksson, H & Olsson, J. Upplevelse och behandling av postoperativ smärta. En litteraturstudie. Examensarbete i omvårdnad 15 högskolepoäng. Malmö högskola: Fakulteten för Hälsa och Samhälle, Institutionen för vårdvetenskap, 2012.Smärta är en upplevelse som är personlig och individuell. Det finns en rad olika faktorer som påverkar upplevelsen av smärta i den postoperativa processen. I denna process har sjuksköterskan ett ansvar att behandla smärta genom sitt omvårdnadsarbete, men trots detta upplever patienter att denna omvårdnad är bristfällig. Syftet med denna litteraturstudie var att undersöka hur postoperativ smärtbehandling utfördes av sjuksköterskorna och hur patienter kan uppleva detta. Metoden var en litteraturstudie med systematisk ansats. Nio artiklar av både kvantitativ och kvalitativ ansats användes. Sökningarna skedde i databaserna Cinahl och PubMed. Resultatet visade att patienterna upplevde att den postoperativa smärtbehandlingen var i behov av förbättring när det gällde individualisering, samt att sjuksköterskorna hade olika attityder till postoperativ smärta vilket gjorde att patienterna fick olika uppfattningar om hur sjuksköterskan behandlade deras smärta. Nyckelord: kirurgi, omvårdnad, postoperativ smärta, smärtbehandling, upplevelse. / Isaksson, H & Olsson, J. Experience and treatment of postoperative pain. A literature review. Degree Project, 15 Credits Points. Nursing Programme, Malmö University: Faculty of Health and Society, Department of Health Care, 2012.Pain is a personal and individual experience. There are several factors that affect the experience of pain in the postoperative process. In this process the nurse has a responsibility to treat pain, despite that; patients perceive this care as defective. The purpose of this study was to explore how the nurses performed postoperative pain treatment and how patients can experience it. The method of this study was a literature review with a systematic approach. Nine studies of both quantitative and qualitative design were used. The searches were performed in two databases, Cinahl and PubMed. The results showed that patients felt that the postoperative pain treatment need of improvement when it comes to individualization and that nurses have different attitudes to postoperative pain, which gave the patients different perceptions of how the nurses treated their pain.Keywords: care, experience, pain treatment, postoperative pain, surgery

Recent evidence appears to indicate that neurons, responsible for our perception of the world around us, are not only electrically excitable, but may have mechanical triggers as well. This is well supported through the growing number of observations of focused ultrasound (FUS) perturbations of the neurons located in our central nervous system (CNS). However, while the CNS is largely responsible for turning electrical signals from the periphery into thoughts and understanding, less is known about the effect of which FUS has upon the peripheral signals themselves: our peripheral nervous system (PNS). Given the non-invasive nature of FUS - were it be discovered to influence neuronal signaling, FUS would become a powerful tool for therapy and medicine, especially in conditions involving pain. Thus, we ponder the question, "How can FUS modulate nerve activity and furthermore, what are the interactions on pain signaling?" In this dissertation, a road-map is described for translating insights acquired through pre-clinical study of ultrasound PNS stimulation to clinical investigation on neuropathic pain modulation in humans. More specifically, methods and tools to study excitation of the sciatic nerve bundle and the dorsal root ganglia (DRG) were built and optimized in rodent models. In turn, these methods and findings enabled investigation into pain signaling and translation to human studies. Finally, FUS was shown to mitigate pain sensations in human patients with neuropathic pain. First, using a newly developed in vivo nerve displacement imaging technique, mechanical deformations of the nerve from FUS stimulation were noninvasively mapped in a two-dimensional plane centered at the sciatic nerve. Nerve displacements were positively correlated with downstream compound muscle activation from FUS sciatic nerve stimulation. Furthermore, by focusing ultrasound waves to the DRGs directly in an ex vivo preparation, additional parameters were identified to modulate spike transmission, effectively regulating high frequency signaling. Next, we investigated the feasibility translating FUS nerve stimulation to clinical studies. We first looked at effects on upstream cortical activity and pain signaling from somatosensory stimuli using high-frequency functional ultrasound (fUS) imaging. FUS was shown to both stimulate somatosensation and suppress pain signaling in the cortex. Secondly, nerve displacement imaging was scaled-up for human investigation, essential for in-procedure localization and stimulation of the targeted nerve bundle. Using a combination of imaging and therapeutic excitation, simultaneous nerve targeting, stimulation, and monitoring was established at pressures required for stimulation. Lastly, clinical feasibility was investigated using previously optimized FUS pulse schemes and scaled-up neuromodulation technologies. Specifically, we applied simultaneous FUS to the median nerve and thermal stimulation to the corresponding dermatome in healthy human subjects. Furthermore, patients with robust and repeatable mechanically-assessed neuropathic pain were similarly stimulated with FUS to assess pain suppression. Based on the findings presented herein, noninvasive FUS peripheral stimulation has the potential for radically shifting the traditional pharmaceutical paradigms in chronic and acute pain treatment by altering signals before being processed in the spinal cord and ultimately the brain. The studies outlined herein serve to elucidate mechanisms of FUS in the PNS, as well as provide the starting foundations for further development of FUS as an effective pain treatment.

Bakgrund: Opioider har använts under lång tid i historien för analgetisk verkan. Opioidanvändning orsakar kroniska förändringar i hjärnans receptorer och ökad tolerans. Långt gången användning kan leda till opioidbrukssyndrom. Vid svår smärta är opioider det enda medicinska alternativet och idag används patientens smärtskattning för att få reda på patientens smärtintensitet. Sjuksköterskans bemötande och attityder är viktigt vid patientnära kontakt för att lägga grunden för god omvårdnad. Syfte: Att belysa sjuksköterskans attityd till att ge smärtbehandling till patienter med opioidbrukssyndrom. Metod: Studien genomfördes som en litteraturstudie med induktiv ansats och nio artiklarna analyserades med hjälp av innehållsanalys. Resultat: Databearbetningen resulterade i fem kategorier och sju underkategorier. Sjuksköterskor hade svårt att veta ifall smärta hos patienter med opioidbrukssyndrom grundade sig i beroende eller smärta av andra orsaker. Samtidigt hade sjuksköterskorna en vilja att lindra smärtan och en uppfattning att ingen skulle behöva lida trots opioidbrukssyndrom. Patientgruppen sågs som krävande och sjuksköterskor upplevde en oro att stå ensam inför beslut i smärtbehandling och vilket beslut som var korrekt. Konklusion: Sjuksköterskors attityder mot patienter med opioidbrukssyndrom var ofta negativa och patientens smärta blev inte betrodd. Sjuksköterskorna uttryckte en utmaning i att veta ifall patienters smärtskattning var reell, samtidigt som patienterna förtjänar smärtlindring. / Background: Opioids have been used throughout history for their analgesic effect. Opioid use causes chronic changes in the brain's receptors and tolerance, prolonged use can lead to opioid use disorder. In case of severe pain, opioids are the only option and today a patient's pain assessment is used to determine a patient's pain intensity. The nurses’ approach and attitudes are important in near patient contact to establish the foundation of good nursing care. Purpose: The purpose of the study was to highlight nurses’ attitudes towards pain treatment of patients with opioid use disorder. Method: The study was carried out as a literature study with an inductive approach and nine articles were analyzed with the help of content analysis. Results: The analysis resulted in five categories and seven subcategories. Nurses had a hard time knowing if a patient with opioid use disorder's pain is caused by addiction or other sources of pain. At the same time, the nurses had a wish to treat the pain and wanted no one to suffer, even though patients had opioid use disorder.  The patient group was regarded as demanding, and nurses experienced concern standing alone taking a decision on their own regarding pain treatment and which decisions were correct. Conclusion: Nurses' attitudes towards patients with opioid use disorder were often negative and they did not believe their patient’s pain. Nurses expressed a challenge in knowing whether the patient’s pain assessment was truthful or not, at the same time they believed patients deserve pain treatment.

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Successful treatment alternatives for chronic pain conditions are limited. One type of chronic pain that can occur is the condition of phantom limb pain, which can occur after the loss of a limb. Many studies have researched the correlation between chronic pain, tactile acuity, and cortical reorganization. Sensory discrimination training has been shown to improve tactile acuity and be beneficial when trying to reduce the intensity and duration of the pain in chronic pain conditions. A device has been developed by the Center for Bionics and Pain Research, and it is intended to train sensory discrimination. How efficiently this device can train sensory discrimination and how much improvements in the tactile acuity in able-bodied participants can be achieved after using the device have been investigated in this study. 16 able-bodied subjects participated in the study. The subjects received five 40 minutes training sessions on five consecutive days. The assessment of the subjects’ tactile acuity was performed before the first training session and after the last training session. The tactile acuity was also assessed after one to two weeks to determine the long-term effect of the training. There were two psychophysical analyses to determine the participants’ tactile acuity, the two-point discrimination test and the monofilament test. The results showed a significant improvement in the two-point discrimination threshold after the five training sessions, thus showing evidence of the improvement in the tactile acuity after using the sensory discrimination training device. There was no significant improvement in the monofilament test.

The major purpose of this study was to determine chronic pain patient's differential use and perceived effectiveness of various cognitive, affective and psychomotor treatment strategies used in the management of pain. Utilizing the TFA System (tm) to determine patient's behavior patterns, a second goal was to determine if treatments were more effective when they matched the behavior pattern. The TFA System is a systematic and integrated approach using thinking (T), feeling (F) and acting (A) components which provides a chance for individual and situation specificity in a treatment situation. The major research questions were addressed through empirical results obtained from a volunteer sample of 39 chronic back pain patients. Five thinking, five feeling, and eight acting treatment methods were examined. T methods were used by slightly more than 50% of the patients, and had the highest frequency of monthly use. F methods were the least used, and had the lowest frequency of use even among those who did use then. Only half of the A methods were used by most of the chronic pain patients, but these were used rather often in a month. Effectiveness for all methods was viewed as being relatively moderate, irrespective of use, with spirituality being perceived as being most effective. Overall, the majority of subjects were not successful in their pain management. Furthermore, there was no relationship between success and personal outlook when a published scale was used to categorize subjects as optimistic or pessimistic. However, based on a self-categorization, almost all the pessimists were not successful, while self-proclaimed optimists were equally likely to be successful as not. There was no apparent relationship between chronic pain patient's behavior profiles and type of treatment methods used. Individual's TFA patterns did not "match" the methods being used to deal with their pain. Overall, no significant differences were revealed in type of treatment method used depending on the demographic characteristics of gender, age, income, education and marital status. Recommendations for both future research and clinical practice were presented. / Ed. D.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, 2014. / BACKGROUND Mechanical neck pain (MNP) has been described as any condition which changes joint mechanics and muscle structure / function. A review of the current literature shows that Muscle Energy Technique (MET) is an effective manual therapy for patients with acute or chronic MNP. The most useful contraction of MET however remains unknown. Some authors advocate the use of a two to seven second MET (Brous, 2005; Greenman, 2003 Mitchell, Moran, and Pruzzo, 1979) whilst other authors have recommended contraction durations of 30 to 60 seconds (Chaitow, 2006; Feland et al., 2001; Bandy and Irion, 1994). This study aimed to establish the most suitable contraction duration of MET in the treatment of chronic MNP by comparing a short duration MET to a long duration MET. OBJECTIVES Objectives included the comparison of a five-second (short duration) MET and a 45-second (long duration) MET in terms of subjective and objective findings in the treatment of chronic MNP. METHOD This randomized clinical trial, with 53 participants utilised a randomization table for group allocation. For the purpose of this study an average of the short contraction durations reported in the literature i.e. five seconds, was used for the short duration MET treatment and an average of the long contraction durations reported in the literature i.e. 45 seconds, was used for the long duration MET. Group A (n=26) received the five-second MET contraction and Group B (n=27) received the 45-second MET contraction treatment. Objective measures included the cervical range of motion (CROM Goniometer) and tenderness levels (algometer). The subjective measures were pain (Numerical Rating Scale-101) and MNP related disability (CMCC Neck Disability Index). Each participant received four treatments over a two week period, with all data collected prior to the first and third consultations and at the final follow up. Data were analysed using the SPSS version 20 (IBM), with a statistically significant p value set at <0.05. Repeated measures ANOVA testing determined the intergroup effects. To assess intergroup effects and effects of the intervention a time x treatment group interaction analysis was conducted. Profile plots assessed direction and trend of the effect of the treatment. RESULTS Intra-group analysis of both groups showed significant improvement in all of the range of motion measures (over time) except for Flexion, Right Lateral Flexion and Left Rotation in Group A and Flexion, Extension, Right Lateral Flexion and Left Lateral Flexion in Group B. The intra-group analysis also showed a significant improvement in the neck disability index scores and the tenderness measurements in both groups. The results of the inter-group analysis revealed that only Left Lateral Flexion showed a significant treatment effect (p=0.011) where increased scores were shown in Group A and not in Group B. There was no treatment effect for the neck disability index scores or the tenderness measurements. CONCLUSION It may be concluded that both treatment protocols were equally effective for all outcomes except for Left Lateral Flexion where the five-second MET seemed to show greater degree of improvement than the 45-second MET. The neck disability index scores and the pain levels of participants in both groups showed an improvement. No treatment was better than the other in terms of these two variables. This therefore seems to support the use of the shorter duration MET in clinical practice.