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Chronic pain is a major health problem affecting more than 1.5 billion people worldwide. Specifically, neuropathic pain and chronic post-surgical pain are debilitating clinical conditions with few efficacious treatments, warranting development of novel therapeutics. Starting with the hypothesis that dysregulated translation regulation pathways may underlie these pain states, we demonstrated that there is a major reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity and increased phosphorylation of mTOR and ERK downstream targets in these persistent pain states. We also hypothesized that activators of AMP-activated protein kinase (AMPK) may represent a novel treatment avenue for the treatment of neuropathic and incision-induced pain because AMPK activators inhibit ERK and mTOR signaling, two important pathways involved in the sensitization of peripheral nociceptors. The AMP activated protein kinase (AMPK) activators, metformin, resveratrol and A769662, inhibited translation regulation signaling pathways in sensory neurons, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. We have further demonstrated that local injection of resveratrol, metformin or A769662 and topical application of resveratrol, a potent AMPK activator, into the hindpaw following plantar incision dose-relatedly reverses incision-mediated mechanical hypersensitivity as well as hyperalgesic priming induced by incision. In addition, co-treatment with systemic metformin and local resveratrol at individually sub-efficacious doses at the time of incision blocked acute hypersensitivity and hyperalgesic priming suggesting potential super-additive effects of combined AMPK activator use. These results highlight the importance of signaling to translation control in peripheral sensitization of nociceptors and provide further evidence for activation of AMPK as a novel treatment avenue for acute and chronic pain states.

Substantial evidence shows that activation of glial cells in the spinal cord may promote central sensitization and enhancement of pain. Descending facilitation from the rostroventromedial medulla (RVM) is also recognized as a critical component in the maintenance of chronic pain states, although the precise mechanisms driving this activity are unclear. Here, we investigated the possibility that glial activation in the RVM could promote descending facilitation from the RVM in states of enhanced pain. Peripheral inflammation was induced with carrageenan injected into the plantar aspect of the hindpaw of male Sprague-Dawley rats and behavioral responses to noxious thermal and light tactile stimuli were determined. Microinjection of the glial inhibitors minocycline or fluorocitrate, or of SB 203580, a p38 MAPK inhibitor, produced a significant and time-related reversal of behavioral hypersensitivity resulting from hindpaw inflammation. Moreover, carrageenan-induced inflammation appeared to produce an increase in immunolabeling for activated microglia and astrocytes in the RVM, as well as for phosphorylated p38 MAPK; the latter was localized to both microglia and neurons of the RVM. Microinjection of the glial inhibitors into the RVM appeared to diminish immunofluorescent labeling for activated RVM microglia and astrocytes. Carrageenan-induced inflammation also increased RVM protein levels of Iba1 and GFAP and administration of minocycline or fluorocitrate into the RVM attenuated this effect. To examine a possible mechanism of glial activation, α, β-methylene-ATP was microinjected into the RVM, inducing thermal hyperalgesia, and pre-treatment with the P2X antagonists, PPADS and TNP-ATP, delayed the initiation of ATP-induced hyperalgesia. Post-treatment with the antagonists had no effect on established ATP-induced or carrageenan-induced hypersensitivity. The activation of P2X receptors initiates a signaling cascade leading to the production and release of nociceptive mediators, including BDNF. The RVM microinjection of an anti- BDNF antibody reversed carrageenan-induced thermal hyperalgesia. A model of morphine-induced paradoxical pain was also used to examine the role of glial activation in the RVM. Sustained morphine administration induced tactile allodynia and RVM microinjection of minocycline, but not fluorocitrate, attenuated the behavioral hypersensitivity. Sustained morphine also induced morphological changes in microglia of the RVM, suggesting microglial activation. A third model of enhanced pain used to study medullary glial activation was the spinal nerve ligation (SNL) model of neuropathic pain. The SNL injury induced astrocyte activation within the RVM and microinjection of the astrocyte inhibitor fluorocitrate attenuated the nerve injury-induced tactile allodynia. Minocycline administered to the RVM did not attenuate the behavioral hypersensitivity, suggesting a role for astrocytes, not microglia, in nerve injury-induced enhanced pain. The data show that inflammatory, opioid-induced and neuropathic pain is associated with glial activation in the RVM which likely participates in driving descending pain facilitation via glial-neuronal communication. These findings reveal a novel site of glial modulation of pain.

Bakgrund: Akupunktur har använts under tusentals år som behandling vid olika sjukdomstillstånd. I Sverige används metoden främst vid smärttillstånd. Författarna vill undersöka akupunktur som omvårdnadsåtgärd genom att belysa patientupplevelsen. Långvarig smärta är ett vanligt, utbrett och komplext problem som är svårbehandlat. Patienter upplever ofta bristfälliga resultat med behandlingen som traditionell medicin erbjuder. Då sjuksköterskan möter smärta dagligen i sitt arbete och har som främsta uppgift att lindra lidande och bör därför vara öppen för olika behandlingsalternativ. Syfte: Undersöka och beskriva patienters upplevelse av akupunktur som omvårdnadsåtgärd hos patienter med långvarig smärta. Metod: Arbetet är en litteraturstudie som består av 12 artiklar. Fem kvantitativa och sju kvalitativa artiklar har studerats med hjälp av innehållsanalys och tre huvudteman utformades. Patienterna över 14 års ålder och artiklar från hela världen inkluderades. Katie Erikssons omvårdnadsteori har använts som teoretisk referensram.  Resultat: Majoriteten av patienterna uttryckte positiva fysiska, psykiska och själsliga upplevelser efter akupunktur behandling, såsom upplevd smärtlindring, avslappning, välbefinnande och personlig utveckling. Patienterna rapporterade att vårdrelationen och det holistiska förhållningssättet var två betydelsefulla aspekter vid behandling. En minoritet av patienterna upplevde ingen förbättring och biverkningar som trötthet och utmattning. Diskussion: Placebons effekt och vårdrelationens betydelse för resultat har diskuterats, då det är otydligt vad den upplevda fysiska smärtlindringen beror på. Följderna för patienterna vid en bristande vårdrelation till vårdgivaren, är att vårdlidande kan uppstå. Vidare har det holistiska förhållningssättet visat på hälsofrämjande faktorer för människan som helhet. Författarna anser sig ha sett paralleller mellan akupunkturens grundtanke och Katie Erikssons omvårdnadsteori. / Background: Acupuncture has been used for thousands of years as treatment for various illness/diseases. In Sweden the method has been used primarily for treating pain. The authors want to examine acupuncture as a caring treatment by focusing on the patients experience. Longterm pain is common, wide spread and complexed problem which is hard to treat. The patient often experience unsatisfactory results with traditional treatments and medicine offered. As a nurse meets patients in pain on a daily bases in her work and her foremost task is to ease pain and it’s therefore necessary to be open to various treatment alternatives.     Aim: To examine and describe the experience of acupuncture as a nursing treatment in patients suffering from long term pain. Method: This analysis is a literature study consisting of 12 articles. Five of these are quantitative and seven qualitative articles have been studied with content analysis and three main themes emerged. Patients over 14 years old and articles from all the world are included. Katie Erikssons caring theory has been used as a theoretical frame of reference.   Results: The majority of patients has expressed positive physical, psychological and spiritual experiences after acupuncture treatment, such as perceived relief of pain, relaxation, well-being and personal growth. Patients reported that the caring relationship and the holistic approach was two important aspects in caring. A minority of patients did not experience improvement and side-effects such as tiredness and exhaustion. Discussion: The placebo effect and the significance of the caring relationship have been discussed as it is unclear what the experienced relief of pain depends on. The consequences for the patients when the caring relationship is lacking is suffering from the care given. Furthermore the holistic approach showed health improving factors for the human as a whole-being. The authors believe they detect parallels between the ground principles of acupuncture and Katie Erikssons caring theory.

Chronic viral infection is a significant burden on healthcare systems worldwide. Robust anti-viral immune responses are essential for viral clearance. Persistent viruses use a variety of mechanisms to evade immune surveillance including the upregulation of host immunesuppressive factors. Secreted fibrinogen-like protein 2 (FGL2) has been identified as an inhibitory effector molecule in suppressing immune responses in patients with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) disease. In a murine model of chronic infection caused by Lymphocytic choriomeningitis virus (LCMV) clone 13, we demonstrate that mice deficient in Fgl2 have increased numbers of mature antigen-presenting cells (APC), improved virus-specific cytotoxic T cell immunity and enhanced viral clearance when compared to wild-type mice. These results highlight the importance of the FGL2 inhibitory pathway in immune evasion and provide a rationale to investigate the effects of blocking FGL2 as a novel immune therapeutic in patients suffering from persistent infections.

The aim of the study was to investigate the application of aspects of Lazarus and Folkman's theory of Stress, Appraisal and Coping, to the chronic pain experience. In this context, the researcher explored the relationship between pain intensity and stress level. The association between pain intensity and the intensity of negative or positive attitudes towards the pain experience was also investigated. In addition, the relationship between pain intensity and the frequency of employing active, problem focused coping-strategies, or passive, emotion focused strategies, was explored. 105 subjects completed the South African Chronic Pain Questionnaire; an assessment tool based on adapted internationally validated measures. Findings suggest that there is a proportional relationship between pain intensity and stress level in the present chronic pain population. A positive relationship between pain intensity and the intensity of negative attitudes was revealed. A positive relationship was also reflected between pain intensity and the employ of passive, emotion-focused coping-strategies. There is a paucity of research that provides a theoretical framework in which to conceptualize the association between stress, appraisal and coping in chronic pain. To this end, the researcher has employed Lazarus and Folkman's theory in order to conceptualize the relationship between these variables and chronic pain intensity. / Thesis (M.A.)-University of Natal, Pietermaritzburg, 2001.

The studies in this dissertation asses age differences in the experience of pain in humans and animals and the appropriateness of pain assessment tools across the adult life-span. Chapter I reviews age differences in experimental, acute and chronic pain in humans. Chapter 2 reviews age differences in the outcome of psychological treatments for chronic pain. It is concluded do there are age differences in each type of pain and that the elderly appear to benefit from psychological treatments as much as younger groups. Several experiments were conducted to examine the concepts that the elderly believe that pain is an inevitable part of aging and are not distressed by it, and that they experience less interim pain than younger patients. However, Chapter 3 presents two studies which find no age differences in pain beliefs. Furthermore, the studies described in Chapters 4 and 5 suggest that there may be age differences in the perceived qualities of chronic pain, measured with the short and full form of the McGill Pain Questionnaire (MPQ), but no age differences in pain intensity measured with single-item scales The data from Chapters 3, 4 and 5 suggest that the affective and cognitive components of chronic pain do not differ among age groups. Analysis of the psychometric properties of the pain measures suggests that verbal descriptor scales of pain intensity and both forms of the MPQ may be appropriate for use across the adult life-span. However, visual analog scales may not be appropriate for use with the elderly. To further elucidate the effects of aging on pain, Chapter 6 reviews age differences in nociceptive responsivity and pain behaviours in the rat. This review suggests that reflexive responses to nociceptive stimuli may not be age dependent although sensitivity on tests of more highly organized behaviours may decrease with age. Chapter 7 presents studies of age differences in the formalin test, a model of tonic pain, which suggest a curvilinear relationship be

Chronic viral infection is a significant burden on healthcare systems worldwide. Robust anti-viral immune responses are essential for viral clearance. Persistent viruses use a variety of mechanisms to evade immune surveillance including the upregulation of host immunesuppressive factors. Secreted fibrinogen-like protein 2 (FGL2) has been identified as an inhibitory effector molecule in suppressing immune responses in patients with chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) disease. In a murine model of chronic infection caused by Lymphocytic choriomeningitis virus (LCMV) clone 13, we demonstrate that mice deficient in Fgl2 have increased numbers of mature antigen-presenting cells (APC), improved virus-specific cytotoxic T cell immunity and enhanced viral clearance when compared to wild-type mice. These results highlight the importance of the FGL2 inhibitory pathway in immune evasion and provide a rationale to investigate the effects of blocking FGL2 as a novel immune therapeutic in patients suffering from persistent infections.

Recorded by Eugene Barsky, Physiotherapy Outreach Librarian, UBC / This is a Systematic Review Presentation titled - "Pain-enduring Eccentric Exercise for the Treatment of Chronic Achilles Tendinopathy", created by Master of Physical Therapy Graduating Students, University of British Columbia - 2006, Presented on September 14-15, 2006 , Vancouver, BC, Canada

Participation in decision-making and inclusion in the important matters of one’s life are upheld as measures of equality and indicators of the moral status of individuals in liberal democratic societies. To some extent, the status of children in western societies is a contested question, and hence, the nature of children’s contributions to decisions is a matter of debate. Evidence suggests that in spite of an apparent societal commitment to children’s participation in the important matters of their lives, children tend to be excluded from decisions in which they might reasonably be involved. This project investigated the participation of one group of children—chronically ill school-age children— in decisions related to their health care. Adopting interpretive description as methodology, data were collected and analyzed through interviews and participant observation with 31 chronically ill children (ages 7 to 12 years) and their parents, as well as through interviews with health care providers. In this study, children’s participation in health care decisions emerged as a complex activity, deeply embedded in relationship and history. Participation varied within two key domains: children’s opportunities and abilities to formulate and make known their intentions and desires in decisional contexts (the resonance of children’s voices); and the standing achieved by children’s views within decisional processes (the relevance of children’s voices). The interplay of adult authority and children’s agency at the nexus of the resonance and relevance of children’s voices created certain participatory spaces, depicted as moral and social realms variously characterized by children’s silence, children’s tangible expression, adult imposed authority, or adult assumed responsibility. The findings of this study demonstrate a need to re-think our concept of children’s participation, and point to the importance of developing a more relational and contextual understanding of how chronically ill children may contribute to important matters in their lives. The findings also support a view that nurses and other health care providers hold certain responsibilities to critically question the relationships and structures that comprise children’s health care encounters, toward a goal of creating conditions where possibilities for children’s participation are optimized.