Abstract PURPOSE: The aim of this study was to describe and compare possible differences regarding selected prognostic factors for disability between patients with non-specific chronic pain who were about to start a multidisciplinary treatment program (MMR), either within primary care (MMR1) or hospital care (MMR2). METHODS: The study had a descriptive and comparative cross sectional design. Eighty-nine patients were recruited consecutively when they were about to start their team treatment (50 in MMR1,39 in MMR2). The measurements were; Evaluation of self-reported self-efficacy for eight daily activities (STIVA-8), The Pain Belief Screening Instrument (PBSI) and Hospital Anxiety and Depression Scale (HADS). RESULTS: The study found some significant differences between the answers from patients in MMR1 and those from patients in MMR2. For instance, patients in MMR2 estimated lower self-efficacy according to STIVA-8 than patients in MMR1. Also, there were fewer low risk patients and more high risk patients in MMR2 than in MMR1 regarding pain intensity according to PBSI. In addition to this, there were fewer patients without depression and more with moderate depression in MMR2 than in MMR1 according to HADS. No significant differences could be shown for either anxiety according to HADS or for low- and high risk regarding activity disability according to PBSI. No significant differences could be found when pain intensity was measured with mean values on a scale from 0-10. CONCLUSIONS: Patients in MMR2 experienced more negative consequences from their pain disease than patients in MMR1. Systematic use of standardized self-reported instruments for selected prognostic factors could be helpful when screening for complexity and make it easier to decide whether the rehabilitation should be within MMR1 or MMR2 for patients in need of MMR. / Sammanfattning SYFTE: Syftet med denna studie var att beskriva och jämföra om patienter med långvarig smärtproblematik inom primärvård (MMR1) respektive specialiserad sjukhusvård (MMR2), som stod i begrepp att påbörja multimodal smärtrehabilitering (MMR), skattade olika avseende ett antal prognostiska faktorer för funktionsförmåga. METOD: Studien hade en deskriptiv och komparativ tvärsnittsdesign. Åttionio konsekutivt tillfrågade patienter deltog (50 i MMR1, 39 i MMR2). Datainsamlingen gjordes vid start av MMR med tre självskattningsformulär; Skattning av tilltro till sin förmåga att utföra åtta specificerade vardagsaktiviteter (STIVA-8), The Pain Belief Screening Instrument (PBSI) och Hospital Anxiety and Depression Scale (HADS). RESULTAT: Studien visade statistiskt signifikanta skillnader avseende att patienterna i MMR2 skattade lägre tilltro till sin förmåga enligt STIVA-8, det var färre andel lågriskpatienter och större andel högriskpatienter i MMR2 avseende smärtintensitet enligt PBSI samt färre andel patienter utan depression i MMR2 och fler med måttliga depressionsbesvär i MMR2 enligt HADS. Inga signifikanta skillnader kunde visas avseende låg- och högrisk för aktivitetsbegränsning enligt PBSI och inte heller för ångest enligt HADS. När smärtintensitet beräknades med medelvärde på skalan 0-10 fanns inga signifikanta skillnader. KONKLUSION: Patienterna i MMR2 skattade mer negativa konsekvenser av sin smärtsjukdom än i MMR1. Systematisk användning av skattningsformulär som ringar in olika prognostiska faktorer bör kunna underlätta selektion och sortering vid val av vårdnivå för patienter i behov av MMR.

Bakgrund: Långvarig smärta är ett stort folkhälsoproblem både internationellt och i Sverige. I Sverige används uttrycket kronisk smärta för att benämna långvarig smärta men det anses idag olämpligt eftersom ordet ”kronisk” associeras med livslång och obotlig smärta. Ofta har personer med långvarig smärta svårt att uttrycka sig och dela sina smärtsamma känslor för någon annan därför känner de sig irriterade, frustrerade, missförstådda, deprimerade. Att lindra lidande hos personer med långvarig smärta är en av sjuksköterskans viktigaste uppgifter. För att kunna förstå hur sjuksköterskan bör hjälpa dessa patienter är det viktigt att studera patienternas upplevelser. Syfte: Syftet med denna studie är att beskriva patientens upplevelser av långvarig smärta Metod: Metoden är en litteraturstudie och baserad på tio kvalitativa artiklar som är publicerade mellan åren 1995-2011. Databaserna som använts är CINAHL, PubMed och Medline. Dataanalysen influerades av Fribergs (2006) bok, Dags för uppsats. Resultat: Resultatet är baserat på fyra huvudkategorier och varje huvudkategori har subkategorier förutom den sista huvudkategorin. I den första huvudkategorin, ”Förändringar i det sociala livet”, beskriver författarna hur en individs sociala liv påverkas av långvarig smärta i förhållande till hans eller hennes familj, vänner och arbete. I övriga huvudkategorier och sex subkategorier redogörs patientens olika känslor och strategier samt dennes upplevelser av vården vid långvarig smärta. Diskussion: Här diskuterar författarna studiens resultat och försöker hålla sig så nära som möjligt till syftet och dessutom kopplar författarna det till Joyce Travelbees omvårdnadsteori om lidande, hopp, sympati och kommunikation.

Litteraturstudiens syfte var att beskriva vilka copingresurser som individer med långvarig smärta använder sig av samt hur dessa resurser förbättrar eller försämrar individernas möjlighet att acceptera sin smärta. Designen för litteraturstudien var deskriptiv och studien baserades på 17 vetenskapliga artiklar med både kvantitativ och kvalitativ ansats. Litteratursökningarna utfördes i databaserna Medline (via PubMed) samt CINAHL. Huvudresultatet visade att individer med långvarig smärta använde sig av inre copingresurser som fysiska och psykosociala copingresurser samt förmågor vid acceptans av långvarig smärta. Individer använde sig även av yttre copingresurser som socialt stöd och materiella copingresurser. Dessa copingresurser kunde förbättra eller försämra individers möjlighet att acceptera långvarig smärta. Litteraturstudiens slutsats belyste vikten av att sjuksköterskan har kunskap om att fysiska, psykiska, sociala och existentiella aspekter genererade smärtupplevelsen. Sjuksköterskan behövde även ha kännedom om copingresurser för att kunna uppmärksamma individens unika förutsättningar och behov. Detta gjorde det möjligt för sjuksköterskan att erbjuda professionellt stöd anpassat efter individens unika copingresurser och hjälpa denne att uppnå acceptans av långvarig smärta. / The aim of the literature rewiev was to describe which coping skills individuals with chronic pain use and how these skills improve or impair the individuals' ability to accept their pain. The design for the literature study was descriptive and the study was based on 17 scientific articles of both quantitative and qualitative approach. The literature searches were carried out in the databases Medline (via PubMed) and CINAHL. The main result showed that individuals with chronic pain use internal skills such as physical and psychosocial skills and abilities to accept chronic pain. Individuals also use external skills such as social support and material resources. These skills can improve or impair individuals' possibility to accept chronic pain. The conclusion highlighted that a nurse should have knowledge about that physical, psychological, social and existential aspects generated the pain experience. A nurse should also have knowledge about coping skills in order to pay attention to the individual's unique circumstances and needs. This enabled the nurse to offer professional support tailored to the individual's unique coping skills and help the individual to achieve acceptance of chronic pain.

Despite intensive research on the neurobiological mechanisms of chronic pain, this therapeutic area remains one of the least satisfactorily covered by current drugs. Glutamate activates two major classes of receptors: ionotropic and metabotropic. Ionotropic receptors are classified into three major subclasses:a-amino-3- hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA). NMDA receptor activation, at the level of the spinal cord and peripheral tissue has been shown to play an important role in the facilitation of nociption in several animal models. Although the efficacy of NMDA receptor antagonists in various experimental and clinical pain situations has been well documented, their use as analgesics is limited by serious side effects such as memory impairment, psychotomimetic effects, ataxia and motor incoordination. Two promising current approaches to obtain effective analgesia devoid of side effects are by subtype-selective NMDA receptor antagonism in central nervous system (CNS) or peripheral use of NMDA receptor antagonist that do not interfere with central glutamate processing. NR2B subunit of NMDA receptor was predominantly found in the superficial dorsal horn of spinal cord. Recent discoveries have revealed that the transfection of small interfering RNAs (siRNAs) into animal cells results in the potent, long-lasting post-transcriptional silencing of specific genes. Thus, two approaches of antagonizing NMDA receptor in CNS and peripheral nervous system (PNS) for pain relief using siRNAs or pharmacological agents are investigated in this study. The first approach involves intrathecal administration of NR2B-siRNA into subarachnoid space and transfection of siRNA into cell of spinal cord by transfection agent of polyethylenimine (PEI). Formalin test was used to induce inflammatory pain in the hind paw of rats. Behavior response to formalin test was observed and recorded on 3rd, 7th, 14th, and 21th day after injection of siRNA. The spinal cords were dissected immediately after formalin test and used for analysis of mRNA and protein. The results revealed that the use of siRNA targeting the NR2B subunit could abolish formalin induced pain behaviors and not impair motor coordination in rat model. The expression of NR2B mRNA and its associated protein as demonstrated by real time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were decreased. Significant reduction of NR2B immunoreactivity in dorsal horn of spinal cord were detected after 7 days treated by NR2B siRNA. The peak effect of gene knockdown occurred on day 3 for mRNA and day 7 for its protein, following intrathecal injection of 5 µg of siRNA targeting NR2B subunit. The inhibition of NR2B mRNA and protein lasted about 14 days and recovered on 21th days after injection of siRNA. The nociceptive response induced by formalin was decreased during the period of downregulation of NR2B protein. A novel intrathecal delivery of siRNA transfected with PEI into cell of dorsal horn reduced formalin-induced pain. The second approach involves subcutaneous injection of NMDA receptor antagonist and topical use of alpha2-adrenergic agonist for abolishing surgical pain. Additionally, we proved the upregulation of glutamate receptors in human inflamed skin. The study examined whether the peripheral ionotropic glutamate receptors (iGluRs) increased in inflamed human skin taken from patients having inflammatory pain over inflamed skin and surrounding area. Real time RT-PCR and western blot were used for quantitation of mRNA and protein of iGluR in normal and inflamed human skin. A significant increase in mRNA and protein for the subunits of NMDA, AMPA, and kainate receptor were detected in inflamed skin when compared to normal skin. The results demonstrate that mRNA and protein level of iGluRs are increasingly expressed during states of persistent inflammation, and that this increased activity may be involved in mediating clinical inflammatory pain in human skin. To examine the postoperative analgesic effect and adverse effect of local NMDA receptor antagonist (ketamine), ketamine (0.3%, 3 ml) or saline was subcutaneous infiltrated pre-incisionally in 26 patients equally assigned to two groups undergoing circumcision surgery. The saline-infiltrated subjects also received 9-mg intramuscular ketamine into the upper arm to control for any related systemic analgesic effects. The postoperative analgesic and adverse effects were followed for 24 hours. For ketamine infiltrated patients, the time interval until first analgesic demand was prolonged and the incidence of pain free (pain score = 0) during movement and erection was significant higher than saline infiltrated patients. No significant differences were noted in the incidence of adverse effects between the two groups. Pre-incisional subcutaneous infiltration of ketamine acting via a peripheral mechanism can suppression postoperative pain after circumcision surgery. Apraclonidine hydrochloride (AH) is a topical, relatively selective alpha2-adrenergic agonist that has limited access to the CNS and exhibits fewer systemic (adverse) effects such as dizziness and hypotension. Eighty patients scheduled for arthroscopic knee surgery received either intraarticular (IA) normal saline, 50 ug IA AH, 150 ug IA AH, or 150 ug IA clonidine subsequent to surgery. The IA application of 150 ug apraclonidine and 150 ug clonidine provide similar degree of postoperative analgesia and similar incidence of adverse effect. The promise is that both approaches attenuating nociception state devoid of CNS adverse effects provide novel approach for the management of chronic pain.

The primary purpose of this study was to find out which variables lie behind the fact that patients who respond well to treatment of chronic pain differs from those who do not. We used logistic regression to predict group belonging based on the self-reported health surveys, i.e if different answers in the surveys can predict whether a patient is “responsive” or “unresponsive”. By bootstrapping 176 samples, and aggregating the results from 176 logistic regressions based on the sub-samples, we calculate an averaged model. The variables anxiety and physical health were significant in 76% and 70% of the models respectively, while depression was significant in 30% of the models. Gender was significant in 15% of the models and health status in 0,006%. The averaged model correctly classified the most unresponsive patients at cut-off value 0.5. As the cut –off value was increased, the number of correctly classified unresponsive patients decreased while the number of correctly classified responsive patients increased, as well as unresponsive patients classified as responsive. We concluded that the model did not discriminate enough between the two groups. We were also interested in finding out how the variables anxiety, depression, heath status, willingness to participate in activities as well as engagement in activities, mental and physical health relate with one another. The results from confirmatory factor analysis showed that a patient’s health status is highly related to their physical health and activity engagement while pain willingness and engagement in activity were least related. Furthermore, the analysis showed that mental health is highly related with anxiety and health status, indicating that mental health is indeed important to reflect upon when considering the health status of a patient.

This qualitative study describes the experience of eight men with fibromyalgia (FM). Data from repeated semi-structured interviews was analysed using the constant comparative method, in order to generate a grounded theory. The specific aims were to explore how individuals perceived and made sense of their condition, and to discover the impact of FM upon their sense of identity and intimate relationships. Two core categories emerged from data analysis - loss and limited understanding. Losses pertained to the men's capabilities and activities; role and identity; work; and relationships. Limited understanding was described in relation to three levels of experience: limited understanding by the individual sufferer; by other people; and by health care professionals. Various intervening and contextual variables were identified for each phenomenon. Analysis suggested that loss is more likely to be pronounced where pain is severe and constant; the degree of incapacity is high; and there is a complete cessation of work. Intervening conditions likely to reduce the sense of loss included role expectations consistent with capabilities; absence of young dependants; a flexible work environment; living with a partner; favourable social comparisons; high self-efficacy and accepting attitude towards illness. Limited understanding was likely to be more pronounced where the individual perceived no rational link between the triggering event and symptoms of FM, and where new difficulties were encountered. The individual was more likely to perceive that others misunderstood their situation if they were not using a mobility aid themselves. Individuals were more likely to perceive limited understanding by the medical profession where the GP had not been especially supportive, and where contact with the specialist was unsatisfactory. Limited understanding was exacerbated by intervening variables including lack of contact with other FM sufferers and a treatment history focusing on 'fixing' the problem. Men with FM struggled to find meaning in their experience. Some individuals were able to locate possible causes, but all the men were unable to fully understand their condition. The analysis suggested that the experience of FM varies for different men. The study reveals that FM is a complex experience characterised by loss, which sufferers and health care professionals struggle to understand. Implications for health care practice and further research are discussed. This study will help FM sufferers understand their condition more fully. Moreover, it should enrich the understanding of health care professionals - thereby facilitating encounters characterised by greater support and empathy for men with FM.

Bakgrund: Långvarig smärta är vanligt förekommande i Sveriges befolkning. Smärtupplevelsen är individuell och påverkas av många dimensioner i livet. Långvarig smärta är svår att bedöma och lindra, den kan skapa ett lidande. Att lindra lidande och främja hälsa hos dessa personer är en viktig men inte alla gånger lätt uppgift för sjuksköterskan. Därför är det nödvändigt med insikter i hur det är att leva med långvarig smärta. Syfte: Syftet med studien var att beskriva upplevelsen av att leva med långvarig smärta. Metod: En litteraturstudie har använts. Studien baseras på tio kvalitativa artiklar som granskats och analyserats med influens av Forsberg och Wengström (2013) samt Friberg (2012). Det vetenskapliga underlaget är hämtat ur databaserna CINAHL och PubMed och är publicerat år 2000-2013. Resultat: Tre huvudteman med subteman representerar resultatet. Första huvudtemat, Känsla av att livet är begränsat, beskriver de negativa förändringar som smärtan leder till, gällande fysiska, psykiska och sociala aspekter. Andra huvudtemat, Strävan efter att bemästra den långvariga smärtan, visar hur varierande strategier används för att bemästra den långvariga smärtan. I tredje huvudtemat, Kampen för att bli betrodd i sitt lidande, framträder smärtans osynlighet som problematisk, misstro i kontakt med närstående och vårdgivare förekommer. Diskussion: Resultatet knyts an till Erikssons omvårdnadsteori om lidande. Sjukdomslidande, livslidande och vårdlidande diskuteras. Försök att lindra, liksom anpassningen av livsmönster och förmågan till försoning belyses. Ensamhet och avskildhet diskuteras samt vikten av att få tid och rum att lida. Omgivningens roll i lidandet samt hur vårdlidande kan lindras berörs även. / Background: Chronic pain is common in the Swedish population. The pain experience is individual and influenced by the many dimensions of life. Chronic pain is difficult to cure and relieve, it causes suffering. To relieve suffering and promote health for these people is an important but not always easy task for the nurse. Therefore, it is necessary to have insight in the experiences related to living with chronic pain. Aim: The aim of this study was to describe the experience of living with chronic pain. Methods: A literature review was used. The study is based on ten qualitative articles that have been investigated and analyzed with influence by Forsberg and Wengström (2013) and Friberg (2012). The scientific evidence is from the databases CINAHL and PubMed and is published year 2000-2013. Results: Three main themes with subthemes represent the result. The first main theme, Feeling that life is limited, describes the negative changes that the pain creates concerning physical, psychological and social aspects. The second main theme, Efforts to overcome the chronic pain, shows that varying strategies are used to overcome the chronic pain. In the third main theme, The struggle to be trusted in their suffering, the invisible pain appears as problematic, suspicion in touch with both family and caregivers occur. Discussions: The result is related to Eriksson´s nursing theory of suffering. The suffering of illness, the suffering of life and the suffering of care is discussed. Attempts to relieve pain as well as adaptation of life patterns and the ability of reconciliation are illuminated. Loneliness and separation is discussed as well as the importance of having time and space to suffer. The role of the fellow people in the suffering, and how the suffering of care may be eased is mentioned as well.

The mechanisms that mediate the maintenance of chronic pain states are poorly understood, but elucidation of such could yield insight into how pain becomes chronic and how the process can potentially be reversed. This thesis investigated the role of ascending and descending spinal dorsal horn circuitry and interneurons in the plasticity that mediates a transition to pathological pain plasticity using hyperalgesic priming model. The results showed that, while dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons mediated IL-6- and carrageenan-induced acute mechanical hypersensitivity, they were not required for PGE₂-induced mechanical hypersensitivity. In stark contrast, ablation of dopaminergic neurons did interrupt the IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE₂ injection failed to cause mechanical hypersensitivity - thereby reflecting that primed state plasticity is driven by differential mechanisms. In addition, the pharmacological antagonism of spinal dopamine D1/D5 receptors reversed priming and its agonism induced mechanical hypersensitivity exclusively in primed mice, which suggests dopaminergic control of pathological pain plasticity in a D1/D5-dependent manner. Moreover, in a primed state, changes to spinal dorsal horn GABA pharmacology were accompanied by upregulation of neuroligin 2 mRNA and protein expression. These findings 1) indicate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity, and 2) point to the inhibitory synaptic expression of neuroligin-2 as the spinal determinants of this type of pain plasticity.

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.