Research projects at Osher
There is a known genetic variant based on a single nucleotide polymorphism that regulates the efficacy of dopamine activation. We have just completed a study where we have demonstrated that subjects sensitization to repeated pain stimuli is much more expressed in subjects with a low capacity for dopamine regulation of the opioid system. This mechanistic study demonstrates that dynamic changes in the pain system also have a genetic underpinning.
Regulation of pain
The individual variations in pain sensitivity have been attributed mostly to ill-defined psychological factors. The results from placebo research have pointed to the descending pain defense system as an important regulator for individual pain sensitivity. This descending system rests on the function of the internal opioid system in the brain. It is known that the efficacy of this system is regulated by the dopamine system. There is a known genetic variant based on a single nucleotide polymorphism that regulates the efficacy of dopamine activation. We have just completed a study where we have demonstrated that subjects sensitization to repeated pain stimuli is much more expressed in subjects with a low capacity for dopamine regulation of the opioid system. This mechanistic study demonstrates that dynamic changes in the pain system also have a genetic underpinning. Data are under publication.
Subjective health decisions
Basic mechanisms of decision making have been investigated in a series of studies. The role of the limbic system alarm mechanisms have been investigated both in economical games The ultimatum game and in a paradigm set for hypothetical bias. We are now expanding this newly developed set of experiments in order to investigate hidden determinants in health seeking behavior.
Placebo exploring the mechanisms beyond consciousness
In a collaborative project between Osher Stockholm and Harvard we are investigating the effects of subliminal cues on the placebo responses. The experiments rests on a previous method that has been employed for analysis of the fear system. Initial experiments demonstrate a robust contextual placebo influence from subliminal cues. First publication in PNAS, second in review.
Acupuncture, placebo and alternative treatments
We published a trial 2011 (Enblom et al) that showed that both standard and sham acupuncture produced strong reductions of nausea and vomiting evoked by cancer radiotherapy. We therefore perform a new series of studies in which the non-specific treatment effects, in particular the patients expectations, will be manipulated through the interaction with the therapist. However, in a present multicenter trial, the interaction between expectation and treatment outcome at cancer chemotherapy will be followed over time. This is based on a model of placebo regarding the brains continuous handling of bodily signals in relation to expectations and past experiences. One such study embarks from theory of brain regulation in placebo to study the trajectory of unspecific effects over time during treatment. The study uses expertise from medical anthropology to set up the interaction schemes between therapist and patient. A parallel study investigates acupuncture in neuropathic pain in cancer patients. In addition, we perform studies regarding attitudes to complementary and alternative treatments (CAM) and prevalence of CAM in a representative population sample.
Acceptance and commitment therapy (ACT) for chronic pain
A series of RCTs and psychometric studies related to treatment of chronic pain in adolescents and adults. ACT is now listed by the American Psychological Association as an evidenced-based (strong level of support for treatment of chronic and persistent pain in general, a development in which the OCIM studies have been important. Several studies are now under way from OCIM collaborations to expand the evidence base for treatment and to understand mechanisms on both biological and behavioral levels of observation. For biological markers, neuroimaging of experimental pain before and after treatment is performed, while blood samples are used to study inflammatory markers.
Treatment of comorbid insomnia
A first study of 130 patients with comorbid (e.g. allergy or pain) insomnia showed that six weeks of cognitive behavioral therapy with a self-help treatment with no or limited therapist support was as efficient as personal therapy for non-comorbid insomnia. Because the mechanisms behind sleep regulation overlap with those involved in inflammatory disorders as well as emotion regulation, this open up for the possibility to treat disordered sleep as part of treating the primary syndrome. As a start, such studies are now started up in adolescent psychiatry and in pain patients, in both cases complemented with biological measures. This complements a set of studies that 1) investigates social interaction in relation to sleep deprivation and sickness and 2) studies the brain´s regulation of sleepiness as well as its handling of social stimuli and empathy after sleep manipulations.
Sleep and upper respiratory tract infections
Observational studies by others and us show that short sleep is associated with increased risk for infections such as the common cold. A putative causal connection is supported by mechanistic studies on the effects of sleep loss. Therefore, we perform a cohort study where we attempt to control and manipulate sleep in naturally occurring respiratory tract infections.
The project addresses the interplay between the nervous and the immune system in healthy individuals and in subjects with chronic inflammatory disorders. The project combines immunological, behavioral and brain imaging competence. After studying acute inflammation with fMRI, we new use PET to capture microglia activation in chronic (allergy and rheumatoid arthritis) inflammation as well as its behavioral consequences. The behavioral read-outs center on pain regulation and subjective health. The project involves several sub-studies and collaborations, including continued studies on microglia activation in chronic pain states. We have recently as the first group shown that acute experimental inflammation increases pain sensitivity in healthy individuals.
Inflammation, sickness and subjective health and pain
Self-rated health is a powerful predictor of mortality, but with little known biological mechanisms. Because diffuse symptoms that are influential on self-rated health resemble a cytokine-induced sickness response, the relation between circulating cytokines and self-rated health is explored in a series of studies in primary care, normal populations, CVD patients, conscripts and patients with asthma. The studies so far confirm our hypothesis that higher level of inflammatory cytokines is related to poor self-rated health, even when controlling for diagnoses and risk factors. The role of the adipose tissue in relation to inflammation and well-being is now also examined in patients that undergo surgical removal of abdominal fat. During 2010 and 2011, both a pilot study of experimental inflammation (administration of endotoxin as a model of an acute sickness response and a main study of 52 participants including fMRI have been conducted (see also under Neuroimmune communication). The studies show that self-rated health, believed to be a relatively stable construct, are acutely regulated in response to inflammation. Earlier studies on subjective health have almost exclusively been using observational designs, why we perform several experimental designs to manipulate the constructs presumed determinants. Apart from inflammation, this is related to manipulations of sleep. Likewise, we study day-to-day co-variations between main factors of interest. One of these studies will use data from the LifeGene project, which aims at studying genes and exposures in 500 000 Swedes in relation to common diseases. OCIM has here accounted for measures of stress, sleep and use of alternative medicine. As a mediator between inflammation and subjective health, the inflammation-driven sickness response is of main interest. We have therefore developed a questionnaire, SicknessQ, to measure the subjective axis in a sickness response. Initial studies show that this construct functions as a mediator between inflammation and subjective health.