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Wellcome Trust conference The Challenges of Chronic Pain

11-13 March 2015
Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

Abstract deadline: 30 January 2015
Registration deadline: 16 February 2015

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Current Research
Functional Imaging in Persistent Pain Models and Chronic Pain Patients
Functional brain imaging has been used to measure the neural correlates of the subjective experience of pain. Non-invasive imaging methods will be used to understand the central mechanisms involved in pain processing and pain relief in humans. The focus will be to dissect the factors that influence nociceptive inputs to alter pain perception in healthy subjects and in patients suffering from chronic pain.

We will examine specific brainstem nuclei in pro- and anti-nociception during cognitive manipulations and chronic pain states. To achieve this, we will apply high-resolution structural and fMRI as well as diffusion tractography to dissect both the functional and anatomical links between key brainstem nuclei (e.g. PAG, nucleus cuneiformis, RVM, PB) and other sub-cortical and cortical structures during administration of topical capscaicin or a psychological/cognitive manipulation. We will also study post opioid-induced hyperalgesia as a model of non-nerve injury that produces a key symptom of neuropathic pain. We hypothesise that this effect is brainstem mediated via descending facilitation. By identifying pain-related regions in humans on a spatial scale near-equivalent to the functional zones reported from electrophysiological studies in animals, we will generate a tight correlation of findings and hypotheses between the animal and human studies.

We will perform fMRI on cohorts of diabetic neuropathy patients with and without pain and the contribution of central sensitisation and the brainstemís descending modulatory system to their clinical pain investigated using various pain fMRI protocols. The patientís state and trait anxiety levels will be included as co-variates in the analysis; the separate contribution of anxiety to the patientís pain can thus be neuroanatomically determined. Further analyses will investigate whether top-down modulation of brainstem regions via anxiety-driven subcortical structures additionally contribute to pain amplification in patients.

Finally, ongoing tonic pain is a key symptom of chronic pain that is notoriously difficult to model and image either in human models or patients using the conventional Blood Oxygen Dependent Level - fMRI, which requires a change in stimulus input (i.e. pain level) during the experiment. We propose therefore to apply whole-brain cerebral blood flow based-fMRI at two time points when ongoing pain is altered (via normal processes or a drug manipulation) to obtain the neural signature of persistent pain in both our capsaicin model in normal as well as selected chronic pain patients.