Chronic pain syndromes with poorly defined radiating pain afflict more than 1/2 of the population of industrialized countries at some point of their lives and may be due to nerve inflammation, or neuritis. In the proposed experiments, the effects of neuritis on sensory axons will be characterized using a single neuron-recording model. Preliminary findings showed that neuritis causes a subpopulation of intact nociceptor axons to become mechanically sensitive, at the site of inflammation.
In Specific Aim 1, we will determine the time course of the induced mechanical sensitivity. Our model of neuritis is characterized by aggregation of macrophages and T-lymphocytes.
In Specific Aim 2, we will determine the time course of the appearance and disappearance of these immune cells, using specific immunohistochemical markers. We will compare this to the time course of the axonal mechanical sensitivity. The process that occurs following axonal damage is called Wallerian degeneration. This process results in aggregation of macrophages within the perineurium and activation of Schwann cells to clear the debris produced by the dead peripheral axons.
In Specific Aim 3, we will test the hypothesis that Wallerian degeneration causes axonal mechanical sensitivity in neighboring, otherwise intact axons. These experiments promise to increase our knowledge of the mechanisms of chronic pain related to neuritis and nerve injury. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR048925-02
Application #
6771829
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Ader, Deborah N
Project Start
2003-07-15
Project End
2007-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$288,575
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Bove, Geoffrey M; Dilley, Andrew (2010) The conundrum of sensitization when recording from nociceptors. J Neurosci Methods 188:213-8
Bove, Geoffrey M; Weissner, Wendy; Barbe, Mary F (2009) Long lasting recruitment of immune cells and altered epi-perineurial thickness in focal nerve inflammation induced by complete Freund's adjuvant. J Neuroimmunol 213:26-30
Bove, Geoffrey M (2008) Epi-perineurial anatomy, innervation, and axonal nociceptive mechanisms. J Bodyw Mov Ther 12:185-90
Dilley, Andrew; Bove, Geoffrey M (2008) Resolution of inflammation-induced axonal mechanical sensitivity and conduction slowing in C-fiber nociceptors. J Pain 9:185-92
Dilley, Andrew; Bove, Geoffrey M (2008) Disruption of axoplasmic transport induces mechanical sensitivity in intact rat C-fibre nociceptor axons. J Physiol 586:593-604
Grigg, P; Robichaud 2nd, D R; Bove, G M (2007) A feedback-controlled dynamic linear actuator to test foot withdrawal thresholds in rat. J Neurosci Methods 163:44-51
Weissner, Wendy; Winterson, Barbara J; Stuart-Tilley, Alan et al. (2006) Time course of substance P expression in dorsal root ganglia following complete spinal nerve transection. J Comp Neurol 497:78-87
Bove, Geoffrey (2006) Mechanical sensory threshold testing using nylon monofilaments: the pain field's ""tin standard"". Pain 124:13-7