MECHANISMS OF NEUROPATHIC PAIN

Summary

Principal Investigator: J C Campbell
Abstract: [unreadable] DESCRIPTION (provided by applicant): Previous studies of neuropathic pain caused by nerve injury have focused on the abnormal properties of the axotomized primary sensory neuron. A proportion of such neurons develop ectopic discharge that can originate at the site of the nerve injury or more proximally in the dorsal root ganglion. Surprisingly, myelinated but not unmyelinated injured afferents exhibit ectopic discharges following a spinal nerve lesion. This has led to the speculation that myelinated fibers acquire the capacity to sensitize central neurons. An alternative mechanism for neuropathic pain comes from studies in our laboratory and others in which ectopic discharges have been found in intact unmyelinated nociceptors that commingle with axotomized axons. This spontaneous activity in unmyelinated afferents may initiate/maintain sensitization of central neurons. Indeed, a number of lines of evidence from preclinical and clinical studies point to a role of uninjured cutaneous nociceptors in neuropathic pain. We propose to address three fundamental questions regarding the properties of these intact, hyperexcitable sensory neurons. First, what kinds of neurons are they? This is important, because some types, like mechanically-insensitive afferents (MIAs) or C-fibers from muscle are believed to have a particularly important role in initiating/maintaining central sensitization. Second, is the transduction mechanism normal in nociceptive afferents or has it become sensitized? Hyperalgesia and allodynia may be due, at least in part, to an enhanced response of primary afferents to natural stimuli. Third, how enduring are these changes in primary afferent neurons? This is important because chronic neuropathic pain could have different mechanisms than acute neuropathic pain. To address these questions, we will perform blinded electrophysiological experiments in a primate model of neuropathic pain. These studies will provide a biological rationale for the development of peripheral treatments for neuropathic pain. [unreadable] [unreadable] [unreadable]
Funding Period: 1978-09-30 - 2010-03-31
more information: NIH RePORT

Top Publications

  1. pmc Mechanisms of neuropathic pain
    James N Campbell
    Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Neuron 52:77-92. 2006
  2. pmc Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat
    Beom Shim
    Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21287, USA
    Pain 128:40-51. 2007
  3. pmc Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury
    Yun Guan
    Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, 720 Rutland Avenue, Ross 350, Baltimore, MD 21205, USA
    Pain 138:318-29. 2008
  4. pmc Conduction properties distinguish unmyelinated sympathetic efferent fibers and unmyelinated primary afferent fibers in the monkey
    Matthias Ringkamp
    Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
    PLoS ONE 5:e9076. 2010
  5. pmc Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense
    Michael D Gershon
    Department of Pathology and Cell Biology, Columbia University, P and S, 630 West 168th Street, New York, NY 10032, USA
    Trans Am Clin Climatol Assoc 123:268-80; discussion 280. 2012

Detail Information

Publications5

  1. pmc Mechanisms of neuropathic pain
    James N Campbell
    Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
    Neuron 52:77-92. 2006
    ..The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders...
  2. pmc Activity-dependent slowing of conduction velocity in uninjured L4 C fibers increases after an L5 spinal nerve injury in the rat
    Beom Shim
    Department of Neurosurgery, Johns Hopkins University, Baltimore, MD 21287, USA
    Pain 128:40-51. 2007
    ..These data provide additional evidence that a nerve injury leads to persistent alterations in the properties of adjacent uninjured, unmyelinated fibers...
  3. pmc Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury
    Yun Guan
    Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, 720 Rutland Avenue, Ross 350, Baltimore, MD 21205, USA
    Pain 138:318-29. 2008
    ..Therefore, peripherally acting MOR agonists may represent a promising therapeutic approach for alleviating neuropathic pain...
  4. pmc Conduction properties distinguish unmyelinated sympathetic efferent fibers and unmyelinated primary afferent fibers in the monkey
    Matthias Ringkamp
    Department of Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
    PLoS ONE 5:e9076. 2010
    ..We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves...
  5. pmc Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense
    Michael D Gershon
    Department of Pathology and Cell Biology, Columbia University, P and S, 630 West 168th Street, New York, NY 10032, USA
    Trans Am Clin Climatol Assoc 123:268-80; discussion 280. 2012
    ..Mucosal 5-HT, therefore, may mobilize inflammatory effectors, which protect the gut from invasion, whereas neuronal 5-HT shields enteric neurons from inflammatory damage...