Recent studies have shown the efficacy and practicality of the integration of complementary and alternative therapies and biomedical treatments for various diseases and illnesses, including high blood pressure, diabetes, epilepsy, and cancer. Saper et al. (2013) demonstrated that once-weekly yoga classes were equally as effective for relieving chronic low back pain in low-income, minority populations than twice-weekly yoga classes. Pain medication data collected from this 12-week study was used to examine the effect of yoga on analgesic use. Pain medications were categorized into four major groups: (1) acetaminophen, (2) opiates, (3) non-steroidal anti-inflammatory drugs (NSAIDS), and (4) other. The average number of NSAID pills taken daily decreased from baseline to 12 weeks. In addition, there was no statistically significant difference in the average number of any type of analgesic taken between once- and twice-weekly yoga groups from baseline to 12 weeks. Our findings suggest that yoga is most useful for individuals with mild to moderate chronic low back pain; however, further studies with more powerful sample sizes must be conducted in order to make more precise conclusions.

The purpose of the current study was to investigate the effects of a multidisciplinary pain management program on five measures of subjective psychosocial factors. Ninety-five participants in the comprehensive multidisciplinary treatment group and the standard medical intervention control group were surveyed about various psychosocial factors using Axis II of the West Haven - Yale Multidimensional Pain Inventory (MPI), pre- to post-treatment. It was hypothesized that post-treatment levels would be significantly lower than pre-treatment levels for all five psychosocial variables. Additionally, gender and ethnicity variables were examined. Based on preliminary analyses indicating pre-treatment differences between the experimental and control group, five 2 x 2 x 3 analyses of covariances (ANCOVAs) were used to examine the above hypotheses. Results indicated significant differences between the treatment conditions on measures of control, with the comprehensive group feeling more in control than the standard group at post-treatment. No other significant main effects for treatment condition were found on the measures of pain severity, interference with daily activities, negative mood, or social support. However, a significant gender main effect was found for social support at post-treatment, with females reporting more social support than males. A significant gender x ethnicity interaction was also found for post-treatment control, with African-American females exhibiting higher levels of control than the other groups. Finally, a significant gender x treatment condition was found for negative mood, with males in the comprehensive group reporting more affective distress than those in the standard group. In this study, control appeared to be an integral factor in the chronic pain sample and greatly improved with comprehensive multidisciplinary treatment; while other areas of relative efficacy were not confirmed in this population.

The primary objective of this study was to examine the association between the theory of planned behavior (TBP) and adherence to a multidisciplinary pain center (MPC) treatment program for chronic pain. While the results of several studies have provided support for the efficacy of MPC treatment in chronic pain, the problems of adherence and attrition are important. TPB is a cognitive/social model of behavior that has been used to predict a variety of behaviors, although it has never been used to predict adherence to a multidisciplinary chronic pain treatment program. It was predicted that Adherence would be predicted by Intentions and that Intentions would be predicted by 1) Perceived Social Norms, 2) Perceived Behavioral Control, 3) Attitudes Toward New Behavior (completing the treatment program), and 4) Attitude Toward Current Behavior (maintaining current treatment and coping strategies). It was found that the total Intentions scores did not predict the total Adherence scores. However, Intentions was predicted by 1) Perceived Behavioral Control, 2) Attitudes Toward New Behavior (completing the treatment program), and 3) Attitude Toward Current Behavior (maintaining current treatment and coping strategies). The finding that Perceived Social Norms did not predict Intentions was consistent with results of previous studies with the TBP. The secondary objective was to examine the extent to which MPC treatment affects patients' attitudes towards behaviors that are associated with successful pain management. The majority of the patients (82%) developed a more favorable attitude toward the program and their average report of the importance of the program was 6.78 on a 10-point scale. The majority of patients (74%) reported experiencing a greater decrease in pain than expected, and the average amount of pain decrease was 5.39 on a 10-point scale.

Dysregulation of low-voltage-activated calcium channels (CaV3.1-CaV3.3) underlies diseases including chronic pain, autism, and hypertension. As a major determinant of protein half-life, the ubiquitin-proteasome system (UPS) may not only cause abnormal CaV3 expression but also be targeted to control channel levels for therapy. There are >600 E3 ubiquitin ligases that catalyse the final step in ubiquitination. A crucial aspect of harnessing the UPS is knowing which E3 ligases regulate a given substrate, and whether their actions are redundant. We report that CaV3.1 and CaV3.2 are distinctively regulated by two NEDD4 family E3 ligases – NEDD4L and Smurf1. Reconstituted CaV3.1 currents were robustly suppressed by Smurf1 but not NEDD4L, whereas CaV3.2 was inhibited by both NEDD4L and Smurf1, concomitant with diminished channel surface density and expression. FRET experiments revealed NEDD4L and Smurf1 interact with distinct loci in CaV3.1 and CaV3.2. Nanobody-mediated targeting of NEDD4L or Smurf1, but not WWP1, HECT domains to CaV3.1 and CaV3.2 strongly suppressed currents through both channels. shRNA knockdown of either NEDD4L or Smurf1 in dorsal root ganglion (DRG) neurons substantially increased both low-voltage and high-voltage-activated calcium channel currents. The results reveal non-redundant regulation of CaV3 channels by NEDD4L and Smurf1; introduce Smurf1 as a potent determinant of ion channel expression; suggest a new mechanism for CaV3.2 up-regulation in chronic pain; and advance leveraging the UPS to control CaV3 expression for therapy.

Doctor of Philosophy / Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed.

Doctor of Philosophy / Despite the demonstrated efficacy of cognitive-behavioural therapy for chronic pain, recent research has attempted to identify predictors of treatment outcome in order to improve the effectiveness of such treatments. This research has indicated that variables such as the nature of the onset of the pain and psychopathology are associated with poor adjustment to chronic pain. Accordingly, these variables might also be predictive of poor response to treatment. Individuals who experience a sudden onset of pain following an injury or accident, particularly when the instigating event is experienced as psychologically traumatic, may present for treatment with high levels of distress, including symptoms consistent with a posttraumatic stress response. The impact of this type of onset of pain and posttraumatic stress symptoms on adjustment to chronic pain and treatment outcome is the focus of this thesis. Three studies were conducted to clarify and extend earlier research findings in this area. Using 536 patients referred for treatment in a tertiary referral pain management centre, the first study examined the psychometric properties of a widely used self-report measure of posttraumatic stress symptoms (the PTSD Checklist, or PCL), modified for use in a chronic pain sample. This study provided preliminary support for the suitability of the PCL as a self-report measure of Posttraumatic Stress Disorder (PTSD) symptoms in chronic pain patients. However, the study also highlighted a number of issues with the use of self-report measures of posttraumatic stress symptoms in chronic pain patient samples. In particular, PCL items enquiring about symptoms which are a common aspect of the chronic pain experience (e.g. irritability, sleep problems) appeared to contribute to high mean scores on the PCL Avoidance and Arousal subscales. Furthermore, application of diagnostic cut-off scores and an algorithm recommended for the PCL in other trauma groups suggested that a much larger proportion of the sample was identified as potentially meeting diagnostic criteria for PTSD than would have been expected from previous research. The second study utilised the modified PCL to investigate the impact of different types of onset of pain (e.g. traumatic onset) and posttraumatic stress symptoms on adjustment to chronic pain in a sample of 196 chronic pain patients referred to the same centre. For patients who experienced the onset of pain related to a specific event, two independent experts in the field of PTSD determined whether these events satisfied the definition of a traumatic event according to DSM-IV diagnostic criteria. Adjustment was assessed through a number of validated measures of mood, disability, pain experience, and pain-related cognitions. Contrary to expectations, comparisons between patients who had experienced different types of onset of pain revealed few significant differences between them. That is, analyses comparing patients presenting with accident-related pain, or pain related to other specific events, to patients who had experienced spontaneous or insidious onset of pain revealed no significant differences between the groups on measures of pain severity, pain-related disability, and symptoms of affective distress after adjustment for age, pain duration, and compensation status. Similarly, comparisons between patients who had experienced a potentially traumatic onset of pain with those who had experienced a non-traumatic or spontaneous or insidious onset of pain also revealed no significant differences on the aforementioned variables. In contrast, compensation status, age, and a number of cognitive variables were significant predictors of pain severity, pain-related disability, and depression. The final study investigated the impact of type of pain onset and posttraumatic stress symptoms on response to a multidisciplinary cognitive-behavioural pain management program. Unlike the previous study, this treatment outcome study revealed a number of differences between onset groups. Most notably, patients who had experienced an insidious or spontaneous onset of pain reported greater improvements in pain severity and maintained these improvements more effectively over a one month period than patients who had experienced pain in the context of an accident or other specific incident. There was also limited evidence that improvements in depression favoured patients who had experienced an insidious or spontaneous and non-traumatic onset of pain. Consistent with this, posttraumatic stress symptoms were a significant predictor of treatment outcome, with higher levels of symptoms being associated with smaller improvements in pain-related disability and distress. Notably, this study also revealed that certain cognitive variables (i.e. catastrophising, self-efficacy, and fear-avoidance beliefs) were also significant predictors of treatment outcome, consistent with previous findings in the pain literature. This provided some perspective on the relative roles of both PTSD symptoms and cognitive variables in adjustment to persisting pain and treatment response. These findings were all consistent with expectations and with previous research. Implications for future research and for the assessment and treatment of chronic pain patients who present with posttraumatic stress symptoms are discussed.

The financial cost for health care and lost productivity due to chronic pain has been estimated at over $70 billion per year. Researchers have attempted to discover the psychosocial and personality factors that discriminate between people who learn to cope well with chronic pain and those who have difficulty adjusting. The purpose of the present study was to examine the effects of perceived locus of control and dispositional optimism on chronic pain treatment outcomes. Subjects reported significantly lower post-treatment pain levels as compared with pre-treatment levels (M = 0.66, SD = 1.58), t(45) = 2.85, p = .007 (two-tailed), but decreased pain was not associated with scores on the internality dimension of the Pain Locus of Control Scale (PLOC) or on the Life Orientation Test-Revised (LOT-R) (a measure of dispositional optimism). Overall, participants' increased coping ability was associated with scores on the LOT-R, but not with scores on the internality dimension of the PLOC. Subjects with the lowest pre-treatment scores on the LOT-R demonstrated significantly greater increases in post-treatment coping ability than those with the highest scores (F(2,40) = 3.93, p < .03). Participants with the highest pre-treatment scores on both the PLOC internality dimension and the LOT-R demonstrated greater post-treatment coping ability (F(2,32) = 4.65, p < .02), but not less post-treatment pain than other subjects. Participants' post-treatment LOT-R scores were significantly higher than their pre-treatment scores (M = 2.09, SD = 3.96), t(46) = 3.61, p = .001 (two-tailed), but post-treatment PLOC internality scores were not significantly higher than pre-treatment scores. Implications of these results are discussed.

The present study explored whether use of Spanish language sayings, or dichos, improved group climate within multi-ethnic chronic pain groups. Use of this form of figurative language fits within psychological theory identifying use of metaphor as a means of promoting change and creating new meaning. Further, metaphor use is consistent with the broader aims of experiential therapy. Group climate was measured by group members' self reports using the Group Climate Questionnaire-Short Form. A pilot study involving Latino Americans in medical and non-medical contexts aided in categorizing dichos as high versus low-relevance. It was anticipated that clients would rate high-relevance sessions as involving greater engagement, and less conflict and avoidance than low-relevance groups. Participants were recruited from four multidisciplinary pain management clinics offering similar programs. Once every four to six weeks, group leaders were provided with a list of either high or low-relevance dichos, and were blind to the existence of dichos categories. Three hierarchical regression analyses were employed to determine whether dichos relevance, characterized as low, mixed or highly relevant, contributed to variance in group conflict, avoidance and engagement. Dichos familiarity was the last variable entered into the regression equation, with gender, ethnicity and acculturation score entered in sequential fashion. Consistent with predictions, low-relevance groups yielded higher conflict scores than all groups combined. Also, high-relevance groups predicted lower avoidance when compared to all groups. In contrast to hypotheses, high-relevance groups predicted lower ratings of group engagement when compared to all groups. Post-hoc analysis indicated the mixed-relevance groups yielded significantly higher engagement scores than the low and high-relevance groups. Implications of these findings are discussed in relation to impact on approaches to group therapy with Latino American clients, and within the chronic pain population. Limitations of the study and recommendations for future research are offered.

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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.