Modulation of central cerebral pain processing by transcranial direct current stimulation (tDCS) using ultra-high field functional magnetic resonance imaging (fMRI) at 7Tesla. .
Transcranial direct current stimulation (tDCS) is a non-invasive method for selective modulation of cortical excitability. There is raising evidence that it has potential therapeutic applications in the field of pain disorders. The aim of this study is to investigate the central after-effects of tDCS on extracranial induced pain stimulation using functional 7 Tesla MRI. Polarity-dependent modulation of central pain processing will be assessed.
The contribution of axonal sensitization to pain and hyperalgesia. NGF- induced changes of signal transformation in human C-fibers.
Nerve growth factor (NGF) is involved in sensitization processes of peripheral C-nociceptors resulting in Hyperalgesia. A role for NGF in neuropathic pain has been proposed, too. In this project long-term effects of intradermal NGF injections on axonal and sensory properties of C-fibers will be assessed by single C-fiber recordings (microneurography) directly in humans. We intend to investigate whether NGF affects both transduction and transformation mechanisms in human nociceptors; whether the two relevant human nociceptor classes are differently affected by NGF and whether NGF effects spread to the untreated branches of the axon.
Examining the functional role of Kv7 sub-types in gastrointestinal pain using a novel human pre-clinical model.
At present, a major limitation in the development of effective therapies for the treatment of abdominal pain is the lack of translation between pre-clinical (animal/cell-based studies) and clinical studies. We propose the Kv7 family of channels, which are involved in somatic pain signaling, have a role in mediating pain within the gastrointestinal tract (GI). The aims of this study are to a) conduct an exploratory functional study examining the role of these channels in the gut using a novel pre-clinical model of visceral pain and b) examine receptor expression within the colon.
Genome-wide association study of pressure pain threshold - a step forward to uncovering genes underlying pain sensation.
This project will contribute to our understanding of the genetic basis of pain by performing genome-wide association study of the pressure pain threshold. Previously genotyped healthy subjects from three population cohorts in Croatia will be re-invited to participate. Expected final sample size for this project is 2,300 subjects. Repeated measurements regression and mixed models analysis will be used in order to adjust for the main confounding variables and familial structure, aiming to further uncover genetic basis of pain sensation.
Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain.
We will test the hypothesis that there is a correlation between disturbances in specific pain mechanisms as assessed by quantitative sensory tests (QST) and analgesic efficacy after single-dose drug administration in patients with chronic low back pain. Genetic factors affecting drug metabolism and pain sensitivity will be analyzed as additional explanatory variables for drug efficacy. We are planning three randomized placebo-controlled sub studies on the antidepressant imipramine, the opioid oxycodone and the anticonvulsant clobazam, conducted in a total of 150 consecutive chronic low back pain patients, who will randomly be assigned to one of the three sub studies.
Pain Sensory Profiles in Diabetic Peripheral Neuropathic Pain.
Diabetes mellitus (DM) is a high profile public health concern because of its complications. Neuropathic pain (NP) is a frequent DM complication, but its pathophysiology is still unclear. Pain sensory profile (SP) (i.e.: the subjective and objective sensory changes associated with pain) may help understanding the pathogenesis of NP and select patients for therapeutic trials. By combining psychophysical, neurophysiological and functional neuroimaging measures, the contribution of peripheral, spinal and brain mechanisms to SPs will be explored in DM patients with NP. Follow-up will indicate whether SP may be predictor and/or marker of peripheral nerve damage in DM.
Investigation of the cerebral neuronal activity in pain-related brain areas of patients with fibromyalgia syndrome and interleukin-4 deficiency using near-infrared spectroscopy.
Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain, tenderness at defined points, and typical associated symptoms. There is evidence for a pathophysiological role of the central pain processing and the immune system. We are investigating the extent and the degree of cerebral activity upon painful stimulation using near-infrared spectroscopy and correlate the findings with systemic interleukin-4 (IL-4) expression as a potential biomarker for FMS. An augmented activation in pain-related cerebral areas is expected correlating with low IL-4 levels.
Pain sensitivity of children with Down's syndrome: Is it really different?
Children with Down's syndrome need frequent surgery for congenital anomalies. Adults with Down's syndrome show altered pain sensitivity compared to controls. Several genes involved in pain perception are known; six of these genes are located on chromosome 21 (ADAMTS5, GRIK1, S100B, RUNX1, KCNE1, KCNJ6). Pain sensation in children with Down’s syndrome could be attenuated or intensified by polymorphisms in these genes. The aim of the project is to explore the relative contribution of these genes to the differences in pain sensitivity of children with Down's syndrome.