The long range objective of this research is to use neurophysiological and psychophysical techniques to develop a better understanding of pain perception. This strategy of correlative neurophysiological and psychophysical studies is a powerful technique to develop an understanding of neural encoding mechanisms. In our research we correlate the response of primary nociceptive afferents, obtained from single fiber recordings in the anesthetized monkey, with the response of human subjects, based on ratings of subjective magnitude. With this approach we have been able to make major inroads regarding the understanding of the peripheral as well as central neural mechanisms of pain and hyperalgesia. These studies provide a foundation to purse research on patients in order to understand and treat neuropathic pain. This proposal builds on prior work by continuing investigations into the role of nociceptors in normal pain sensation and by continuing neurophysiological and psychophysical studies of the mechanisms of hyperalgesia at the site of injury (primary hyperalgesia) and of hyperalgesia in the uninjured skin surrounding an injury (secondary hyperalgesia). These studies of primary and secondary hyperalgesia form the basis for investigations of hyperalgesia in neuropathic pain, a common and debilitating form of chronic pain. Numerous questions will be probed to address such issues as: (1) how does the branching structure of nociceptors affect signal processing? (2) What is the basis of fatigue in nociceptors? (3) Capsaicin is a potent drug in causing pain and hyperalgesia but also has therapeutic potential. Which classes of nociceptors signal the pain from capsaicin, and which classes are vulnerable to the toxic effects of capsaicin? (4) Two models of secondary hyperalgesia will be tested to gather information about the likely central nervous system mechanisms of this pathological feature of pain. (5) Finally these studies of hyperalgesia in normal volunteers will be directly applied to test highly focused hypotheses regarding the mechanisms and possible treatments of neuropathic pain in patients. This hypothesis driven research interrelates basic and clinical research in a mater that has excellent potential for promoting the understanding and treatment of pain.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1 (01))
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Kitt, Cheryl A
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Johns Hopkins University
Schools of Medicine
United States
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Gershon, Michael D (2012) Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense. Trans Am Clin Climatol Assoc 123:268-80; discussion 280
Ringkamp, Matthias; Johanek, Lisa M; Borzan, Jasenka et al. (2010) Conduction properties distinguish unmyelinated sympathetic efferent fibers and unmyelinated primary afferent fibers in the monkey. PLoS One 5:e9076
Guan, Yun; Johanek, Lisa M; Hartke, Timothy V et al. (2008) Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury. Pain 138:318-29
Shim, Beom; Ringkamp, Matthias; Lambrinos, George L et al. (2007) Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat. Pain 128:40-51
Campbell, James N; Meyer, Richard A (2006) Mechanisms of neuropathic pain. Neuron 52:77-92
Ringkamp, Matthias; Meyer, Richard A (2005) Injured versus uninjured afferents: Who is to blame for neuropathic pain? Anesthesiology 103:221-3
Slugg, Robert M; Campbell, James N; Meyer, Richard A (2004) The population response of A- and C-fiber nociceptors in monkey encodes high-intensity mechanical stimuli. J Neurosci 24:4649-56
Lancelotta, Mary Pat; Sheth, Rishi N; Meyer, Richard A et al. (2003) Severity and duration of hyperalgesia in rat varies with type of nerve lesion. Neurosurgery 53:1200-8; discussion 1208-9
Peng, Yuan B; Ringkamp, Matthias; Meyer, Richard A et al. (2003) Fatigue and paradoxical enhancement of heat response in C-fiber nociceptors from cross-modal excitation. J Neurosci 23:4766-74
Sheth, Rishi N; Dorsi, Michael J; Li, Yongbo et al. (2002) Mechanical hyperalgesia after an L5 ventral rhizotomy or an L5 ganglionectomy in the rat. Pain 96:63-72

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