Treatment of last resort? Psychological therapy seeking in chronic pain patients.

OBJECTIVE: Our goal was to assess how many chronic pain patients seek psychological treatment for their condition and what psychological and demographic characteristics are associated with that decision. METHODS: The association between pain intensity, quality of life and psychological treatment seeking was tested in two hypothetical models which differed according to beliefs about either external or internal control over pain. RESULTS: A minority of patients had experience with psychological treatment of chronic pain. Patients who had that experience were younger, suffered from more intense pain, and applied many more coping strategies than patients who never tried this kind of treatment. Intense pain and low quality of life motivated chronic pain patients to seek psychological treatment only if they believed that doctors could control their pain. DISCUSSION: The study results stress the importance of diversifying the methods used to treat chronic pain and educating patients about the benefits of psychological treatment. Low numbers of chronic pain patients who take advantage of psychological treatment indicate that encouragement from medical professionals might be necessary.

Age as a moderator in the interplay among locus of control, coping, and quality of life of people with chronic pain.

OBJECTIVE: Identifying the factors that determine the quality of life of patients with chronic pain is an integral part of developing interventions to reduce the negative impact of persistent pain. Locus of control (LoC) could play an important role in adaptation to prolonged pain, but the results of studies are inconsistent. We examined the link between pain LoC and quality of life. Moreover, we investigated whether the relationship between LoC and quality of life is mediated by passive and active coping, and whether age moderates the LoC-coping relationship. METHODS: The study was cross-sectional, and variables (internal, chance and powerful-others LoC, pain coping strategies, average pain intensity, and quality of life) were assessed via questionnaires in a sample of 594 individuals (67% females) with chronic pain who were 18-72 (mean: 36) years of age. RESULTS: Mediation and moderated mediation analyses were conducted. Internal and external LoC were associated, respectively, with better and with worse quality of life. Passive coping mediated the association between the powerful-others dimension of LoC and poor quality of life. Additionally, indirect effects of internal LoC on quality of life via passive and active coping were found. The relationship between the powerful-others dimension of LoC and coping was stronger for middle-aged and older individuals than for younger individuals. CONCLUSIONS: This study contributes to a better understanding of the mechanisms linking LoC with quality of life of patients with chronic pain. Depending on the age, control beliefs might translate differently into strategies used to cope with pain, and thus into quality of life.

When one suffers less, all suffer less: Individual pain ratings are more effective than group ratings in producing placebo hypoalgesia.

BACKGROUND: Placebo hypoalgesia can be induced by observing a person (model) whose pain relief is the result of the use of an inert substance or procedure. This study examined whether verbal modelling, that is, showing pain ratings provided by other people, is sufficient to induce placebo hypoalgesia. METHODS: Participants from the experimental groups were acquainted with pain ratings (presented on VASs) derived from a single person (groups 1 and 3) or a group of people (groups 2 and 4) that were allegedly subjected to the same painful procedure. The ratings of pain stimuli that were allegedly applied with placebo were lower than the ratings of stimuli applied without placebo. In two of the experimental groups (group 3 and 4), participants also watched a video recording showing individuals who allegedly provided pain ratings; however, they did not observe them undergoing pain stimulation. The control group did not undergo any manipulation. Then, the participants received a series of the same thermal pain stimuli that were applied either with or without placebo and rated their intensity. RESULTS: Placebo hypoalgesia was induced only in participants presented with pain ratings provided by a single person, regardless of whether this person was previously seen. However, the pain ratings presented to the participants generally decreased individual pain sensations, regardless of whether they came from a group of people or a single person. CONCLUSIONS: Verbal modelling can produce placebo hypoalgesia and reduce pain sensations. It may be effectively used in clinical practice to modify patients' responses to pain treatment. SIGNIFICANCE: This study shows that knowledge about pain ratings provided by another person is sufficient to induce placebo hypoalgesia; thus, neither direct nor indirect observation of a person experiencing pain is necessary to induce this effect. Pain ratings derived from a group of people can decrease pain sensations but they do not produce placebo hypoalgesia.

Order does matter: the combined effects of classical conditioning and verbal suggestions on placebo hypoalgesia and nocebo hyperalgesia.

ABSTRACT: In most experimental studies in which verbal suggestion and classical conditioning are implemented together to induce placebo effects, the former precedes the latter. In naturally occurring situations, however, the information concerning pain does not always precede but often follows the pain experience. Moreover, this information is not always congruent with experience. This study investigates whether the chronology of verbal suggestion and conditioning, as well as their congruence, affects placebo hypoalgesia and nocebo hyperalgesia. The effects induced in 15 groups were compared. The participants in 8 experimental groups were presented with verbal suggestions that were either congruent or incongruent with classical conditioning. The verbal suggestions were provided either before or after conditioning. In 2 other experimental groups, placebo conditioning or nocebo conditioning was implemented without any verbal suggestion; in 2 groups, verbal suggestion of hypoalgesia or hyperalgesia without conditioning was applied. The control groups without any suggestions or conditioning were also included. Placebo hypoalgesia induced by congruent procedures was significantly stronger when the suggestion of hypoalgesia preceded rather than followed conditioning. The order of the congruent procedures did not affect the magnitude of nocebo hyperalgesia. In the groups in which incongruent procedures were implemented, placebo hypoalgesia or nocebo hyperalgesia was in line with the direction of the last-used procedure, regardless of whether it was conditioning or verbal suggestion. The results show that not the type of the procedure (verbal suggestion or conditioning), but the direction of the last-used procedure shapes pain-related expectancies and determines placebo effects.

One of us or one of them? The effects of the model's and observer's characteristics on placebo analgesia induced by observational learning.

Previous studies have proved that observational learning can induce placebo analgesia, but the factors that influence observationally induced placebo analgesia have not yet been extensively examined. The primary goal of this study was to investigate the effect of information about the role that the observed person (model) plays in the experiment on the magnitude of the observationally induced placebo effect. This study also examined the contribution of the observer's empathy, conformity and fear of pain to the placebo analgesia induced by observational learning. The effects induced in two experimental groups and one control group were compared. Participants in the experimental groups observed a model introduced as either another participant taking part in the study or a coworker of the experimenter. The model rated the intensity of pain induced by electrocutaneous stimuli preceded by color stimuli. One-half of all participants watched a model rating pain stimuli preceded by the color orange as higher than stimuli preceded by the color blue; for the other half, the ratings were the opposite. There was no observation in the control group. Subsequently, all participants received pain stimuli of the same intensity preceded by orange and blue stimuli and rated the intensity of the experienced pain. Placebo analgesia was found in both experimental groups. However, the way the observed model was introduced to participants did not affect the magnitude of placebo analgesia. Thus, the study showed that the role played by the model is not crucial for observationally induced placebo analgesia. The examined observer's individual characteristics did not predict the magnitude of placebo effect.

Reaction to the death of the oldest female in a group of chimpanzees at the Municipal Zoological Garden, Warsaw.

In March 2017, the oldest female of a group of chimpanzees living in the Municipal Zoological Garden in Warsaw, died in her sleep at the age of 53, due to natural causes. The article reports reactions of the eight other individuals in the group, four males and four females, including the daughter and the granddaughter of the old female, the following day. The corpse generally elicited more interest in the females than in the adult males. The females touched the body gently and groomed it more often than the males, who tended simply to look at and sniff it. However, the most diverse reactions, ranging from gentle touching to jumping on and hitting the corpse, were seen in the youngest male. By contrast, the oldest male never approached the corpse. In general, the chimpanzees at the zoo reacted in a manner much milder than is often reported from the wild.

Memory of pain in adults: a protocol for systematic review and meta-analysis.

BACKGROUND: The way pain is remembered and reported can affect medical decisions taken by patients and health-care professionals. Memory of pain has been investigated extensively for the past few decades; however, the results of previous studies are highly variable, indicating that the recollection of pain can be accurate, overestimated or underestimated. It is therefore difficult to conclude how well pain is remembered. The aim of this systematic review and meta-analysis is to summarize research findings on memory of pain in healthy adults and patients suffering from acute and chronic pain. METHODS: The systematic review will be performed by searching for articles indexed in the following databases: PubMed, MEDLINE, PsycINFO, Web of Science, ScienceDirect, PsycARTICLES, Scopus and Academic Search Complete. Studies will be included if (1) they investigated healthy adults or patients with any acute or chronic pain condition and if (2) they assessed experienced pain (pain intensity and/or pain unpleasantness) and its recollection. No restrictions related to the date of publication and recall delay will be applied. Studies will be screened for eligibility and risk of bias by two independent assessors. The risk of bias will be assessed by a modified Downs and Black checklist. A narrative synthesis will be performed in the first stage; in the second stage, the results of studies with comparable designs will be pooled in meta-analytical syntheses. DISCUSSION: The question of whether pain is remembered accurately is crucial for valid pain diagnosis, effective treatment and prognosis. So far, a number of studies on memory of pain have been conducted; however, a definitive conclusion on whether memory of pain is accurate is still lacking. In this systematic review and meta-analysis, available data will be pooled together to further inform research and clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018093523.

Why is running a marathon like giving birth? The possible role of oxytocin in the underestimation of the memory of pain induced by labor and intense exercise.

Pain can be overestimated, underestimated or reported accurately at recall. The way pain is remembered seems to depend on certain factors, including the type of pain or, in other words, its cause, the context, and the meaning it has for the person suffering from it. For instance, episodes of chronic pain, as well as pain related to surgery, are often overestimated at recall. Interestingly, research shows that pain induced by parturition or marathon running is often underestimated at recall despite the fact that both are not only physically grueling but also emotionally intense experiences. However, both processes can likewise be considered positive events, as opposed to most that involve pain. On the neurophysiological level, one of the similarities between giving birth and running a marathon is the particular involvement of the oxytocin system. Oxytocin is involved both in parturition and intense exercise, for various reasons. During labor, oxytocin mediates uterine contractions, while in the case of extensive running it might be involved in the maintenance of fluid balance. It also has well-documented analgesic properties and plays an important role in memory formation and recall. It has been suggested that oxytocin modulates the output of the central nucleus of the amygdala (CeA) during the fear recall. Moreover, it has been demonstrated that oxytocin can impair fear learning and influence the memory of both positive and negative emotionally salient stimuli. We propose that the reason for pain to be remembered in a more favorable light is the central action of oxytocin in the central nucleus of the amygdala, first and foremost during the encoding phase.

Wnt/ß-Catenin Signaling Induces Integrin α4ß1 in T Cells and Promotes a Progressive Neuroinflammatory Disease in Mice.

The mechanisms leading to autoimmune and inflammatory diseases in the CNS have not been elucidated. The environmental triggers of the aberrant presence of CD4+ T cells in the CNS are not known. In this article, we report that abnormal ß-catenin expression in T cells drives a fatal neuroinflammatory disease in mice that is characterized by CNS infiltration of T cells, glial activation, and progressive loss of motor function. We show that enhanced ß-catenin expression in T cells leads to aberrant and Th1-biased T cell activation, enhanced expression of integrin α4ß1, and infiltration of activated T cells into the spinal cord, without affecting regulatory T cell function. Importantly, expression of ß-catenin in mature naive T cells was sufficient to drive integrin α4ß1 expression and CNS migration, whereas pharmacologic inhibition of integrin α4ß1 reduced the abnormal T cell presence in the CNS of ß-catenin-expressing mice. Together, these results implicate deregulation of the Wnt/ß-catenin pathway in CNS inflammation and suggest novel therapeutic strategies for neuroinflammatory disorders.

Mapping pathological phenotypes in a mouse model of CDKL5 disorder.

Mutations in cyclin-dependent kinase-like 5 (CDKL5) cause early-onset epileptic encephalopathy, a neurodevelopmental disorder with similarities to Rett Syndrome. Here we describe the physiological, molecular, and behavioral phenotyping of a Cdkl5 conditional knockout mouse model of CDKL5 disorder. Behavioral analysis of constitutive Cdkl5 knockout mice revealed key features of the human disorder, including limb clasping, hypoactivity, and abnormal eye tracking. Anatomical, physiological, and molecular analysis of the knockout uncovered potential pathological substrates of the disorder, including reduced dendritic arborization of cortical neurons, abnormal electroencephalograph (EEG) responses to convulsant treatment, decreased visual evoked responses (VEPs), and alterations in the Akt/rpS6 signaling pathway. Selective knockout of Cdkl5 in excitatory and inhibitory forebrain neurons allowed us to map the behavioral features of the disorder to separable cell-types. These findings identify physiological and molecular deficits in specific forebrain neuron populations as possible pathological substrates in CDKL5 disorder.

Enhanced fear expression in Spir-1 actin organizer mutant mice.

Spir proteins nucleate actin filaments at vesicle membranes and facilitate intracellular transport processes. The mammalian genome encodes two Spir proteins, namely Spir-1 and Spir-2. While the mouse spir-2 gene has a rather broad expression pattern, high levels of spir-1 expression are restricted to the nervous system, oocytes, and testis. Spir-1 mutant mice generated by a gene trap method have been employed to address Spir-1 function during mouse development and in adult mouse tissues, with a specific emphasis on viability, reproduction, and the nervous system. The gene trap cassette disrupts Spir-1 expression between the N-terminal KIND domain and the WH2 domain cluster. Spir-1 mutant mice are viable and were born in a Mendelian ratio. In accordance with the redundant function of Spir-1 and Spir-2 in oocyte maturation, spir-1 mutant mice are fertile. The overall brain anatomy of spir-1 mutant mice is not altered and visual and motor functions of the mice remain normal. Microscopic analysis shows a slight reduction in the number of dendritic spines on cortical neurons. Detailed behavioral studies of the spir-1 mutant mice, however, unveiled a very specific and highly significant phenotype in terms of fear learning in male mice. In contextual and cued fear conditioning experiments the male spir-1 mutant mice display increased fear memory when compared to their control littermates. Our data point toward a particular function of the vesicle associated Spir-1 actin organizer in neuronal circuits determining fear behavior.

Sensitized phenotypic screening identifies gene dosage sensitive region on chromosome 11 that predisposes to disease in mice.

The identification of susceptibility genes for human disease is a major goal of current biomedical research. Both sequence and structural variation have emerged as major genetic sources of phenotypic variability and growing evidence points to copy number variation as a particularly important source of susceptibility for disease. Here we propose and validate a strategy to identify genes in which changes in dosage alter susceptibility to disease-relevant phenotypes in the mouse. Our approach relies on sensitized phenotypic screening of megabase-sized chromosomal deletion and deficiency lines carrying altered copy numbers of ∼30 linked genes. This approach offers several advantages as a method to systematically identify genes involved in disease susceptibility. To examine the feasibility of such a screen, we performed sensitized phenotyping in five therapeutic areas (metabolic syndrome, immune dysfunction, atherosclerosis, cancer and behaviour) of a 0.8 Mb reciprocal chromosomal duplication and deficiency on chromosome 11 containing 27 genes. Gene dosage in the region significantly affected risk for high-fat diet-induced metabolic syndrome, antigen-induced immune hypersensitivity, ApoE-induced atherosclerosis, and home cage activity. Follow up studies on individual gene knockouts for two candidates in the region showed that copy number variation in Stat5 was responsible for the phenotypic variation in antigen-induced immune hypersensitivity and metabolic syndrome. These data demonstrate the power of sensitized phenotypic screening of segmental aneuploidy lines to identify disease susceptibility genes.