The adverse interaction between smoking and chronic pain has been known for decades. A variety of chronic pain conditions – ranging from headache to low back pain to fibromyalgia – markedly exacerbate smoking prevalence and intensity in packs per day among multiple patient populations. In patients seeking pain treatment, the prevalence of smoking approaches 50%, compared to less than 20% in the general population. Perhaps not surprisingly, the relationship is bidirectional: not only does persistent pain increase rates and intensity of smoking, but smoking also appears to exacerbate both the intensity and associated impairment of chronic pain. In fact, smoking appears to place individuals at risk for developing a chronic pain condition and may also facilitate the transition from acute to chronic pain. The growing body of literature documenting these associations has led to the proposition of a positive feedback loop: individuals smoke in part to cope with their pain, but smoking actually worsens the pain. Despite the strong evidence for the existence of this adverse interaction, the mechanisms responsible for it remain poorly understood. A number of preclinical and clinical studies have documented that nicotinic acetylcholine receptor (nAChR) agonists, e.g., nicotine, have analgesic efficacy in the acute pain setting, such as that produced experimentally in the research laboratory or experienced by patients postoperatively. In contrast, the role of nAChR activation in modulating chronic pain is less well characterized. The experiments described in this thesis determine whether persistent pain diminishes the antinociceptive (analgesic) efficacy of an α4β2 nAChR agonist in the rostral ventromedial medulla (RVM), a key brainstem pain modulatory nucleus, and subsequently begin to elucidate the mechanisms by which persistent pain elicits this plasticity. The complete Freund’s adjuvant (CFA) model of chronic pain was employed to test the hypothesis that persistent inflammatory injury diminishes the antinociceptive efficacy of the selective and potent α4β2 nAChR agonist epibatidine in key brainstem pain modulatory nuclei. Paw withdrawal latency to a noxious heat stimulus was used to evaluate the anti-hyperalgesic and antinociceptive effects of epibatidine microinjected in the RVM or periaqueductal gray (PAG) of male rats. The effects of epibatidine were assessed both in uninjured animals and in animals at different times after intraplantar CFA injection. Interestingly, pretreatment with an α4β2-selective antagonist demonstrated that the antinociceptive effects of epibatidine in naïve rats were mediated by α4β2 nAChRs in the RVM but not in the PAG. While the antinociceptive effects of epibatidine in the RVM were abolished after two weeks of inflammatory pain, the anti-hyperalgesic effects remained unchanged. Surprisingly, epibatidine no longer appeared to be acting primarily at α4β2 nAChRs as early as four hours after injury. Persistent inflammation did not alter the anti-hyperalgesic or antinociceptive effects of epibatidine in the PAG. Radioligand binding studies were conducted to test the most parsimonious hypothesis that a global reduction in α4β2 nAChR number or binding affinity during persistent injury was in part responsible for the decreased efficacy of epibatidine in the RVM after intraplantar CFA. Saturation binding using [3H]-epibatidine in membrane homogenates prepared from RVM and PAG tissue revealed no differences in receptors between saline- and CFA-treated rats at any time after injury, suggesting that a whole-nucleus reduction in nAChRs could not explain the observed behavioral phenomena. To query functional changes with greater resolution, whole-cell patch clamp electrophysiology was employed to begin assessing the consequences of nAChR activation by nicotine at the level of the neuron. Initial studies performed in the locus coeruleus demonstrated that all neurons responded to nicotine with an inward current that desensitized with continued exposure to the drug. Neurons in the RVM exhibited significantly more heterogeneity in their response to nicotine: desensitizing inward currents were seen in some; sustained outward currents in others; inward currents followed by outward currents in a third population; and still others had no response to nicotine exposure. The sustained outward currents persisted in the presence of the sodium channel blocker tetrodotoxin, were not blocked by an α4β2 nAChR-selective antagonist, and appeared to be mediated by G protein-coupled receptors and potassium channels. Taken together, the present results demonstrate that persistent inflammatory injury produces adaptive changes in nicotinic signaling in the RVM such that the antinociceptive effects of epibatidine activation are abolished in a time-dependent manner. These changes cannot be attributed to a whole-nucleus reduction in α4β2 nAChRs. However, nicotinic signaling in the RVM is complex, and small alterations in the pre- or postsynaptic actions of nicotine may have significant ramifications for the overall nociceptive sensitivity of an animal. The data presented here suggest that plasticity in nicotinic signaling within the bulbospinal pain modulatory pathways may in part explain the adverse interaction between smoking and chronic pain observed in humans.

Magister Scientiae (Physiotherapy) - MSc(Physio) / Evidence indicates that the current physiotherapy management of patients with chronic non-specific LBP only offers moderate benefit. Combined treatment programmes, addressing body as well as the mind, shows promising results in developed countries with adequate resources but low evidence in poorly-resourced countries and contexts. This is another gap in the existing knowledge. The study aimed to evaluate the effectiveness of a combined physiotherapy and cognitive-behavioral therapy treatment, compared to physiotherapy alone, in reducing pain, disability, mental health and fear-avoidance behavior, in adults with non-specific low back pain. The systematic review included articles published, in English only, between 1985-2018 (July) in the following databases available at the University of The Western Cape: EbscoHost, BioMedCentral, Cambridge Journals Online, CINAHL, Cochrane Library, Medline (EbscoHost), Medline (Pubmed), Sabinet Reference, SAGE Journals Online, ScienceDirect,SciFinder Scholar, SCOPUS, Wiley Online Library, Springerlink and PubMed.Two reviewers independently evaluated the methodological quality of full text articles, using a critical appraisal tool. Fourteen (14) articles were included based on methodological rigour. Five (5) articles were included in the narrative synthesis and nine (9) articles were included in the meta-analyses. Statistically significant improvements in pain, disability and mental health, in favour of combination therapy for patients with chronic lower back pain were found. A small but statistically significant cumulative effect size for mental health (g = -0.26, Z = -4.49, p <.01) , physical disability (g = -0.27, Z = -5.09, p <.01) and pain (g = -.27, Z = -5.05, p <.01) , in favour of a combination of cognitive behavioural therapy and physiotherapy in patients with chronic lower back pain was found. In addition, a medium but statistically significant cumulative effect size (g = -0.50, Z = -6.95, p <.01), in terms of fear avoidance, was found in favour of the combination therapy. In conclusion, physiotherapy in combination with cognitivebehavioral therapy was more effective than physiotherapy alone, in reducing pain, disability, mental health and fear-avoidance behaviour, in adults with non-specific low back pain. Ethics: Permission for the study was obtained from the university’s Biomedical Research Ethics Committee.

An understanding of pain presupposes that the sufferer is able to use a language which is understood by all. Pain is always described in the language of experience and this experience, encountered by all, is nevertheless lived alone. The interpretive process provides the framework for this study which explores the experiences of five persistent pain sufferers. They have not had their pain validated by diagnosis and persistent pain has become the centrepiece of their existence. The use of epiphany moments illuminates an understanding of the essence of persistent pain experiences, and sufferers are provided with a voice to tell their own stories as their experiences unfold through events in time. These stories are then deconstructed and analysed in order to bring meaning to the lives described. This study found that the communal folklore of pain remains underpinned by dominant ideological forces and discursive practices which sustain the powerlessness of persistent pain sufferers. The sufferer is rendered powerless through medical technologies including the medical interview. Through language the perception of pain is understood and translated in such a way as to cause the sufferer to question the validity of their experience while accepting blame for the persistence of their pain and the need to have it stop. It was postulated that resistance to this process provides the mechanism through which persistent pain sufferers are able to surrender previously held notions of self to alternate identities, which encapsulate the embodied experience of pain. The sufferer can then move to a position where their persistent pain experience is validated. / Doctor of Philosophy (PhD)

The current research was a randomised two group (control and treatment) study that evaluated the effectiveness of an ACT-based self-help book for people with chronic pain. Over a 6-week period, 6 participants read the book and completed exercises from it with weekly telephone support while 8 others waited. Five of these others began the intervention after a 6-week control period. Participants completed pre- and post-intervention questionnaires for acceptance, values illness, quality of life, satisfaction with life, depression, anxiety and pain. Initial outcome data were collected for 8 control participants and 6 intervention participants. A total of 11 participants completed pre- and post-intervention measures. Participants' who read the book, rated the content of the book each week according to reading level and usefulness, and their comprehension of the content was also assessed. Original group data showed statistically significant improvement in acceptance and quality of life for those who completed the intervention. Once the data were pooled, statistically significant improvements in acceptance, quality of life, satisfaction with life, and values illness were found. In general, using the self-help book did not result in reduced pain, depression or anxiety, although for some individuals gains were made in these areas. Individual perceptions of the book components were varied but findings suggest that cognitive defusion and mindfulness were parts of the book that participants found hard. The current findings support the hypothesis that using the self-help book would add value to the lives of people who experience chronic pain. Thus, the book may be a useful tool for people who experience chronic pain.

Objectives: Electro-acupuncture (EA) has been demonstrated to be effective in reducing post-operative acute consumption of opioid-like medications (OLM) by previous studies. This effect has not been examined in patients with chronic pain. In this thesis, a randomised, double-blind, sham acupuncture-controlled study was reported. The trial aimed to evaluate the effect of EA in reducing OLM consumption in patients with chronic non-malignant pain. Methods: Thirty-five patients were recruited from a multidisciplinary pain management clinic in Melbourne. After a two-week baseline assessment, participants were randomly assigned to one of the two groups by a computer generated randomisation sequence: real EA (REA, n = 17) or sham EA (SEA, n = 18). The REA group received 2/100 Hz EA stimulation on two pairs of acupoints (Zusanli ST36 and Fenglong ST40 on one leg and Hegu LI4 and Quchi LI11 on one arm) and manual acupuncture on an additional five chosen acupoints for 30 minutes. The SEA group received superficial needling on non-acupoints without Deqi sensation or electrical stimulation. Both groups received treatment twice a week for six weeks. Participants were followed up for 12 weeks at intervals of four weeks. During the trial, participants were given clear instructions on how to reduce their OLM usage. A researcher telephoned the participants three times during the trial to encourage them to reduce OLM intake. The assessor, researcher and participants were blinded to treatment allocation. Outcome measures: The primary outcome measures included OLM consumption, related side effects, dosage of non-opioid analgesics and the intensity and unpleasantness of pain. These measures were recorded daily for two weeks before the intervention, six weeks during the treatment period and three times during the follow up period. Secondary outcome measures were depression and quality of life as assessed by the Beck Depression Inventory-II (BDI-II) and the Medical Outcome Study 36-Item Short Form (SF-36), respectively. Data were analysed with independent t-tests or analysis of variance (ANOVA) where appropriate and per protocol analysis was employed. Results: Nine participants withdrew from the study. At baseline, the two groups were comparable on all demographic characteristics and major outcome variables except for the average intensity of pain. During the treatment period, the reduction of OLM consumption was more rapid in the REA group (64%) than in the SEA (46%) (ANOVA, p less than 0.05). The effect was maintained for four weeks in the REA group. There were no differences in the improvement of all other measures between the two groups. The incidence of EA-related adverse events (AEs) per treatment was 21% and 10% in the REA and SEA groups, respectively. All AEs were minor. Over 90% of the participants were satisfied with the treatments given and would recommend EA to others. The blinding was successful. Conclusions: EA could be an effective and safe treatment for reducing OLM consumption for patients with chronic pain, and may be used as an adjunct therapy in chronic pain management. Further studies with larger sample sizes are warranted.

<p>The aim of this study was to compare perceived disability in daily activities, anxiety and depression for patients with chronic pain (>3 month), before and after rehabilitation. Another aim was to examine if there were any correlations between disability in daily activities and the extent of anxiety and depression before and after rehabilitation.</p><p>For the measurements, Disability Rating Index (DRI) that measures disability in daily activities, and Hospital Anxiety and Depression Scale (HADS) ) which measures the extent of anxiety and depression were used. The study was carried out with 50 patients who had suffered from chronic pain and with the objective to return to work after rehabilitation. Of these, 90 % were female. The measurements were carried out at three measure points; before rehabilitation, seven weeks after rehabilitation and one year after rehabilitation.</p><p>The main result did not show any statistically significant improvement in ability to perform daily activities.</p><p>The only significant difference that emerged was an improvement in anxiety seven weeks after rehabilitation compared with before. There were significant correlations between the ability to perform daily activities and anxiety and depression before rehabilitation. There was also a significant correlation between the ability to perform daily activities and depression after rehabilitation.</p><p>Conclusions drawn from this paper are that there seems to be a decrease in feelings of anxiety after rehabilitation and also that there appears to exist a correlation between disability and depression.</p>

The aim of this study was to compare perceived disability in daily activities, anxiety and depression for patients with chronic pain (&gt;3 month), before and after rehabilitation. Another aim was to examine if there were any correlations between disability in daily activities and the extent of anxiety and depression before and after rehabilitation. For the measurements, Disability Rating Index (DRI) that measures disability in daily activities, and Hospital Anxiety and Depression Scale (HADS) ) which measures the extent of anxiety and depression were used. The study was carried out with 50 patients who had suffered from chronic pain and with the objective to return to work after rehabilitation. Of these, 90 % were female. The measurements were carried out at three measure points; before rehabilitation, seven weeks after rehabilitation and one year after rehabilitation. The main result did not show any statistically significant improvement in ability to perform daily activities. The only significant difference that emerged was an improvement in anxiety seven weeks after rehabilitation compared with before. There were significant correlations between the ability to perform daily activities and anxiety and depression before rehabilitation. There was also a significant correlation between the ability to perform daily activities and depression after rehabilitation. Conclusions drawn from this paper are that there seems to be a decrease in feelings of anxiety after rehabilitation and also that there appears to exist a correlation between disability and depression.

Chronic pain conditions can be extremely challenging to deal with in the workplace. The implications of these conditions extend far beyond the employees themselves and can create significant organizational impacts. The Chronic Pain Self-Management Program was developed by Dr. Sandra LeFort, and was originally based on the generic Stanford model of self-management. The six-week program, delivered weekly, is designed to explore and instruct those with chronic pain on different aspects of their condition. This pilot study used a mixed method design to evaluate the effectiveness of Chronic Pain Self-Management Program in the workplace. The quantitative measures for this study were unable to demonstrate the effectiveness of the workshop due to a lack of statistical significance. Through the qualitative measures it was possible to delve into how the chronic pain condition manifests itself in the workplace and what support systems are available for those with chronic pain. There are definitely some positive implications from this pilot research, but through further research it is possible to truly understand how people live with chronic pain in the workplace and how their conditions can be made more manageable. / UOIT

Chronic pain in the aged is a widespread phenomenon, and morphine is the most commonly used narcotic analgesic for treatment. Despite that fact, there are relatively few published studies examining the impact of advanced age on morphine analgesia. We hypothesized that aged rats would be less sensitive to morphine than adults, and that aged animals would have reduced mu-opioid receptor (MOR) binding and expression in the ventrolateral periaqueductal gray, a brain region responsible for morphine analgesia. Using a model of persistent inflammatory pain, we found that morphine was significantly less effective in aged males compared to adult males, and that aged males and females experience a reduction in MOR binding and expression compared to adults. These results suggest that there are clear age differences in morphine efficacy, and that reductions in MOR binding and expression in the periaqueductal gray could underlie those differences.

The Chronic Pain Center (CPC) in Saskatoon offers a multidisciplinary treatment program whose goals are to facilitate improved coping skills, function and well-being, and to promote self-reliant lifestyles. They have documented a statistically significant improvement on several measures of physical and social functioning at the completion of the six week program, but to date have no formal evaluation of the long term effects.<p/> The purpose of this study was to re-evaluate the CPC clients (treatment group) at least one year following their completion of the treatment program to determine if they had maintained those improvements and also to compare them to the group of clients (control group) who underwent initial multidisciplinary assessment at the Centre, but did not attend the six week treatment program. Evaluation by mail out questionnaires assessed several important aspects of chronic pain. A 34% response rate resulted in 142 participants for this study.<p/> Data analyses involved a multi-stage process of univariate, bivariate and multivariate analyses. For the first goal, evaluating changes in the treatment group over time, the outcome variables considered had been administered at three points in time: admission to the CPC program, discharge from the six week program, and at study follow-up. For the second goal, the treatment and control groups were compared at one point in time; the study follow-up.<p/> The study demonstrated that the scores on all outcome variables used in the follow-up study improved significantly from the time of assessment to the time of discharge for the clients who attended the CPC treatment program. These improvements declined over time, but remained significantly improved from the admission scores. (Wilks Ë=.501, F(1,48)=4.788, p=.000) However, the study was unable to demonstrate any significant differences between the treatment and control groups on any of the outcome measures at the time of the study follow-up.(Wilks Ë=.930, F (1,107) = 1.014, p=.430) There were several limitations to this study, including the use of a non-randomized control group and the method of recruitment, which may have introduced bias into the study and affected the ability to effectively explain this finding.<p/>