PaIN Lab Research
Psychophysics refers to the quantitative study of the relationship between stimulus and sensation. In the pain research field, the term is virtually synonymous with Quantitative Sensory Testing (QST), a term popularized over the last few decades. The history of psychophysics is, however, much richer, dating back to the mid 1800s with the work of Ernst Weber and Gustav Fechner. Thus, some of the techniques used by our lab were developed before psychology was established as its own scientific discipline. Psychophysical techniques can reveal fundamental insights about the function of the nervous system and the underpinnings of perception. For example, Helmholtz used psychophysics to correctly predict that there are three visual pigments in the retina that contribute to color vision more than a century before this fact was validated using neurophysiological techniques. It is incredibly important to put people's subjective perceptions of pain and other stimuli at the forefront of what we do. There will be no time in the foreseeable future when brain scans or other "objective" physiological measures will replace the gold standard of systematically inquiring about individuals' subjective experiences. Our lab takes great care to precisely quantify the sensory experiences of our participants. In addition to measuring threshold and suprathreshold responses to noxious stimuli, our lab also conducts experiments on innocuous somatosensory stimulation (touch, vibration, cool, warmth), auditory tone perception, and visual sensitivity.
Neuroimaging techniques allow researchers to get a glimpse inside of the human brain using relatively non-invasive methods. By combining a variety of brain neuroimaging methodologies, our lab is able to look at structural morphology, metabolic and neurochemical composition, and function (e.g. response to painful stimuli) in the brains of individuals with and without chronic pain. In some cases we test the effects of experimental manipulation of these features by pharmacologic compounds, other sensory stimuli, expectation, or other means. Neuroimaging is an excellent complement to psychophysical investigations, enabling us to dig down to examine the physiologic mechanisms in which people's experiences of experimental and chronic pain are rooted. Our lab does many magnetic resonance imaging (MRI)-based techniques including functional MRI, voxel based morphometry (VBM), resting state and evoked functional connectivity, and proton magnetic resonance spectroscopy. We also plan on doing some positron emission tomography (PET) imaging in Emory's brand new combined PET/fMRI scanner.
Peripheral Nerve Morphology
In order to gain a more complete picture of the somatosensory system, in some studies we also obtain measures of peripheral small nerve fiber density and morphology. These are the fibers in the body that transmit signals concerning temperature, pain, and itch to the central nervous system. The traditional way to gain access to these fibers is to take a small skin biopsy, usually from the ankle, and count the number of nerve fibers and branches in a section of epidermis. Additionally, it is possible to get a measure of peripheral nerve morphology with a less invasive method, in vivo, using a specialized confocal microscope that takes pictures of the nerve fiber layer of the cornea (clear covering on the eye). This technique, called corneal confocal microscopy, often detects abnormalities in small nerve fibers that are correlated with those observed in skin biopsies, like we found in patients with fibromyalgia and a subset of patients who experience sensations of chronic dry eyes but who have normal tear production.
Many of our studies involve individuals who have various forms of chronic pain. Dr. Harper has been involved with studies of fibromyalgia, temporomandibular disorder, chronic pelvic pain, knee osteoarthritis, and others. In some cases this research is cross-sectional, meaning we compare a group of patients with a certain chronic pain condition to a group of individuals without chronic pain, to better understand what differences in sensory processing and the somatosensory system may increase one's propensity to have chronic pain. Understanding this could help us develop better treatments for pain when new mechanisms of chronic pain are indicated. In addition, we are also interested in running clinical trials, longitudinal treatment studies for chronic pain using pharmacological and non-pharmacological treatments and often comparing responsiveness with a placebo control group who does not receive the experimental treatment. Many of the measures we collect could potentially be suitable "pain biomarkers". Finding biomarkers for pain is important because it may help us better understand why a treatment works well in some individuals with chronic pain but not others. Numerous lines of evidence suggest that factors in the spinal cord and brain often contribute greatly to chronic pain. On the other hand, studies have detected abnormalities in the peripheral nervous system in individuals with some chronic pain conditions, like fibromyalgia. Finally, psychophysics (aka QST) has uncovered numerous ways in which individuals with chronic pain process experimental pain, and in some cases innocuous sensory information, differently. The output of the nociceptive system (i.e. the pain experience) is the culmination of a variety of factors that can increase or decrease pain at many points along the signals' path. Therefore, the Harper PaIN Lab's experimental toolbox, combining psychophysics, brain imaging, and peripheral imaging, helps our Lab build a window through which we are able to look, from a fairly unique viewpoint, at how pain is processed at multiple levels of the nervous system. Ultimately, we hope that our discoveries will help provide relief to those who suffer from chronic pain.
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