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Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation.

Publication ,  Journal Article
McKelvey, R; Berta, T; Old, E; Ji, R-R; Fitzgerald, M
Published in: The Journal of neuroscience : the official journal of the Society for Neuroscience
January 2015

Peripheral nerve injury can trigger neuropathic pain in adults but not in infants; indeed, for unknown reasons, neuropathic pain is rare before adolescence. We show here that the absence of neuropathic pain response in infant male rats and mice following nerve injury is due to an active, constitutive immune suppression of dorsal horn pain activity. In contrast to adult nerve injury, which triggers a proinflammatory immune response in the spinal dorsal horn, infant nerve injury triggers an anti-inflammatory immune response, characterized by significant increases in IL-4 and IL-10. This immediate anti-inflammatory response can also be evoked by direct C-fiber nerve stimulation in infant, but not adult, mice. Blockade of the anti-inflammatory activity with intrathecal anti-IL10 unmasks neuropathic pain behavior in infant nerve injured mice, showing that pain hypersensitivity in young mice is actively suppressed by a dominant anti-inflammatory neuroimmune response. As infant nerve injured mice reach adolescence (postnatal day 25-30), the dorsal horn immune profile switches from an anti-inflammatory to a proinflammatory response characterized by significant increases in TNF and BDNF, and this is accompanied by a late onset neuropathic pain behavior and increased dorsal horn cell sensitivity to cutaneous mechanical and cold stimuli. These findings show that neuropathic pain following early life nerve injury is not absent but suppressed by neuroimmune activity and that "latent" pain can still emerge at adolescence, when the neuroimmune profile changes. The data may explain why neuropathic pain is rare in young children and also why it can emerge, for no observable reason, in adolescent patients.

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Published In

The Journal of neuroscience : the official journal of the Society for Neuroscience

DOI

EISSN

1529-2401

ISSN

0270-6474

Publication Date

January 2015

Volume

35

Issue

2

Start / End Page

457 / 466

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Spinal Cord Dorsal Horn
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Neuroimmunomodulation
  • Neuralgia
  • Mice
  • Male
  • Interleukin-4
 

Citation

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McKelvey, R., Berta, T., Old, E., Ji, R.-R., & Fitzgerald, M. (2015). Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 35(2), 457–466. https://doi.org/10.1523/jneurosci.2315-14.2015
McKelvey, Rebecca, Temugin Berta, Elizabeth Old, Ru-Rong Ji, and Maria Fitzgerald. “Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 35, no. 2 (January 2015): 457–66. https://doi.org/10.1523/jneurosci.2315-14.2015.
McKelvey R, Berta T, Old E, Ji R-R, Fitzgerald M. Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015 Jan;35(2):457–66.
McKelvey, Rebecca, et al. “Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, vol. 35, no. 2, Jan. 2015, pp. 457–66. Epmc, doi:10.1523/jneurosci.2315-14.2015.
McKelvey R, Berta T, Old E, Ji R-R, Fitzgerald M. Neuropathic pain is constitutively suppressed in early life by anti-inflammatory neuroimmune regulation. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2015 Jan;35(2):457–466.

Published In

The Journal of neuroscience : the official journal of the Society for Neuroscience

DOI

EISSN

1529-2401

ISSN

0270-6474

Publication Date

January 2015

Volume

35

Issue

2

Start / End Page

457 / 466

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Spinal Cord Dorsal Horn
  • Rats, Sprague-Dawley
  • Rats
  • Neurology & Neurosurgery
  • Neuroimmunomodulation
  • Neuralgia
  • Mice
  • Male
  • Interleukin-4