PERIPHERAL NOCICEPTORS IN INFLAMMATORY PAIN

Research project

Description

Dorsal root ganglion (DRG) neurons are involved in the
transmission of nociceptive information from peripheral tissues to
the central nervous system. A class of these sense organs differ
from all others in that they display a property called
"sensitization" wherein the response to successive noxious stimuli
increases and the threshold is lowered - the opposite of
"adaptation". Recently several neuropeptides known as
tachykinins (substance P, substance K, and neuromedin K) have
been shown to be synthesized by mammalian DRG neurons.
Recent data has strongly implicated these neuropeptides in the
afferent transmission of nociceptive information and in the
efferent regulation of inflammation and sensitization in
peripheral tissues. In addition another powerful vasodilator,
calcitonin gene related peptide (CGRP), has been shown to co-
exist with substance P containing DRG neurons and appears to
potentiate the nociceptive actions of substance P in the rat spinal
cord. The hypothesis we will test in the present proposal is
whether tachykinin and CGRP-containing DRG neurons change
biochemically and pharmacologically in response to an
inflammatory pain state, and if so, to what extent these changes
are associated with the phenomena of sensitization. The model
system we will use to investigate this will be a standard
experimental arthritis in the rat which will serve as a simple,
reproducible and humane animal model of a chronic pain syndrome
of high incidence in man. The goal of the present proposal is
clear; to understand how peripheral tachykinin and CGRP
containing neurons are involved in the genesis of chronic pain and
inflammation in arthritis and to determine the effectiveness of
the 30 known putative tachykinin antagonists in ameliorating the
pain or inflammation associated with the arthritic condition. We feel the proposed work is the most tangible, direct and
quantitative approach for studying those factors which might
activate nociceptors in ordinary innocuous joint movement;
obviously a problem of practical importance.
StatusActive
Effective start/end date4/1/872/29/20

Funding

  • National Institutes of Health
  • National Institutes of Health: $327,822.00
  • National Institutes of Health: $324,778.00
  • National Institutes of Health
  • National Institutes of Health: $427,397.00
  • National Institutes of Health
  • National Institutes of Health: $478,165.00
  • National Institutes of Health: $424,779.00
  • National Institutes of Health: $257,088.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $194,358.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $393,230.00
  • National Institutes of Health: $436,993.00
  • National Institutes of Health: $160,117.00
  • National Institutes of Health: $324,778.00
  • National Institutes of Health: $300,672.00
  • National Institutes of Health
  • National Institutes of Health: $74,250.00
  • National Institutes of Health: $205,728.00
  • National Institutes of Health
  • National Institutes of Health: $184,632.00
  • National Institutes of Health: $402,801.00
  • National Institutes of Health: $330,313.00
  • National Institutes of Health: $383,941.00

Fingerprint

Nociceptors
Pain
Bone and Bones
Inflammation
Neurons
Bone Neoplasms
Substance P
Spinal Ganglia
Spinal Cord
Opiate Alkaloids
Non-Steroidal Anti-Inflammatory Agents
Neurokinin-1 Receptors
Chronic Pain
Sensory Receptor Cells
Tachykinins
Arthritis
Colon
Calcitonin Gene-Related Peptide
Bone Fractures
Neuropeptides

Keywords

  • Medicine(all)
  • Neuroscience(all)