Faculty Research

Pamela E Paulson, PhD
Research Assistant Professor, Neurology

Research Interest: Neurobiology of chronic pain: Supraspinal mechanisms and therapeutic treatments.

My research in the last decade has focused on the neurobiology of chronic pain. To investigate the mechanisms responsible for human neuropathic pain, it is necessary to employ appropriate animal models, which mimic most, if not all of the symptoms observed in the human condition. Using a technique developed in our laboratory for imaging localized changes in cerebral blood flow (rCBF) in awake rats we have shown that autoradiographic estimates of regional rCBF can be used to simultaneously identify pain-specific alterations in the activation of multiple forebrain structures in animal models of acute (formalin test) and chronic (CCI, SCI and diabetes) pain. Our studies have revealed unique patterns of changes in rCBF that are associated with the perception of pain, providing insight into the function of the pain network as a whole; information which was previously unattainable from clinical data or individual pharmacological, stimulation, lesion or electrophysiological experiments.

My current research is focused on characterizing the mechanisms of pain in type 1 and type 2 diabetes. Prior to the brain imaging experiments, all of our animals undergo comprehensive behavioral testing to assess spontaneous locomotor behavior and mechanical and thermal sensitivity. We have recently added an operant behavioral paradigm to our methods of assessment of chronic pain, allowing us to evaluate the more complex aspects of pain perception. In addition, we have begun behavioral experiments to assess the influence of voluntary exercise (running wheel activity) on pain sensitivity and to evaluate exercise as a viable treatment method for neuropathic pain. Other alternative treatment options we are/will be using include treatment with antioxidants or diet modifications.

In conjunction with our behavioral experiments and following our imaging experiments, we are using immunohistochemical methods to assess neuronal morphology and apoptosis, thus providing an integrative model to assess behavior, functional activation and apoptotic activity all within the same animal. These experiments will identify whether there is a positive relationship between forebrain activation, apoptosis and the presence of persistent pain.

I am currently performing several pilot studies that are of significant importance to me. The first is a pilot study to evaluate the effects of spontaneous running wheel activity on pain processing and recovery from traumatic injury. Exercise has been shown to be beneficial to overall health, perhaps due to its ability to enhance immune responses in man and animals. Specifically, voluntary wheel running results in a significant upregulation of brain-derived neurotrophic factor (BDNF), a neurotrophin that participates in cellular maintenance and in activity-dependent plasticity. Second, I am completing a series of experiments characterizing the effects of the anesthetics that are commonly used in animal fMRI to assess the influence of these drugs on nociceptive processing. Lastly, I am expanding the work in our laboratory to include age-related changes in pain perception. Persistent pain is very common in the elderly, due to both the cumulative effect of progression of chronic painful diseases and the frequency of many painful conditions increases with age. The International Association for the Study of Pain has recently identified research on pain in relation to ageing as a top priority. However, to date, very little research has focused on supraspinal mechanisms of age-related pain

Selected references:

Paulson PE, Minoshima S, Morrow TJ, Casey KL. Gender differences in pain perception and patterns of cerebral activation during noxious heat stimulation in humans. PAIN 1998, 76 (1,2) 223-229.

Morrow TJ, Paulson PE, Danneman P, Casey KL. Imaging Pain: An Animal Model Using Regional Cerebral Blood Flow. PAIN, 1998, 75 (2,3) 355-365.

Morrow TJ, Paulson PE, Brewer KL, Yezierski RP, Casey KL. Chronic, selective forebrain responses to excitotoxic dorsal horn injury. Exp. J Neurol. 2000, 161, 220-226.

Paulson PE, Morrow TJ, Casey KL, Bilateral Behavioral and Regional Cerebral Blood Flow Changes During Painful Peripheral Mononeuropathy in the Rat. PAIN 2000, 84 (2,3) 233-246.

Paulson PE, Morrow TJ, Casey KL, Long Term Changes in Behavior and Regional Cerebral Blood Flow Associated with Painful Peripheral Mononeuropathy in the Rat. PAIN 2002, 95 31-40.

Lorenz J, Cross DJ, Minoshima S, Morrow TJ, Paulson PE, Casey KL. A Specific Human Forebrain Response During C Fiber-Mediated Heat Allodynia. Neuron 2002. 35: 383-393.

Hong S, Morrow TJ, Paulson PE, Isom LL, Wiley JW: Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat., J. Biol. Chem., 2004, 279: 29341-29350.

Paulson PE, Gorman AL, Yezierski RP, Casey KL Morrow TJ. Differences in Forebrain Regional Cerebral Blood Flow in Two Strains of Rat At Rest and After Spinal Cord Injury., Exp. Neurol. 2005, 196 (2): 413-421.