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T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice.

Publication ,  Journal Article
Rosen, SF; Ham, B; Drouin, S; Boachie, N; Chabot-Dore, A-J; Austin, J-S; Diatchenko, L; Mogil, JS
Published in: J Neurosci
October 11, 2017

It has been reported consistently that many female chronic pain sufferers have an attenuation of symptoms during pregnancy. Rats display increased pain tolerance during pregnancy due to an increase in opioid receptors in the spinal cord. Past studies did not consider the role of non-neuronal cells, which are now known to play an important role in chronic pain processing. Using an inflammatory (complete Freund's adjuvant) or neuropathic (spared nerve injury) model of persistent pain, we observed that young adult female mice in early pregnancy switch from a microglia-independent to a microglia-dependent pain hypersensitivity mechanism. During late pregnancy, female mice show no evidence of chronic pain whatsoever. This pregnancy-related analgesia is reversible by intrathecal administration of naloxone, suggesting an opioid-mediated mechanism; pharmacological and genetic data suggest the importance of δ-opioid receptors. We also observe that T-cell-deficient (nude and Rag1-null mutant) pregnant mice do not exhibit pregnancy analgesia, which can be rescued with the adoptive transfer of CD4+ or CD8+ T cells from late-pregnant wild-type mice. These results suggest that T cells are a mediator of the opioid analgesia exhibited during pregnancy.SIGNIFICANCE STATEMENT Chronic pain symptoms often subside during pregnancy. This pregnancy-related analgesia has been demonstrated for acute pain in rats. Here, we show that pregnancy analgesia can produce a complete cessation of chronic pain behaviors in mice. We show that the phenomenon is dependent on pregnancy hormones (estrogen and progesterone), δ-opioid receptors, and T cells of the adaptive immune system. These findings add to the recent but growing evidence of sex-specific T-cell involvement in chronic pain processing.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

October 11, 2017

Volume

37

Issue

41

Start / End Page

9819 / 9827

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Opioid, delta
  • Pregnancy, Animal
  • Pregnancy
  • Ovariectomy
  • Neurology & Neurosurgery
  • Neuralgia
  • Narcotic Antagonists
  • Naloxone
  • Microglia
 

Citation

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Rosen, S. F., Ham, B., Drouin, S., Boachie, N., Chabot-Dore, A.-J., Austin, J.-S., … Mogil, J. S. (2017). T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice. J Neurosci, 37(41), 9819–9827. https://doi.org/10.1523/JNEUROSCI.2053-17.2017
Rosen, Sarah F., Boram Ham, Shannon Drouin, Nadia Boachie, Anne-Julie Chabot-Dore, Jean-Sebastien Austin, Luda Diatchenko, and Jeffrey S. Mogil. “T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice.J Neurosci 37, no. 41 (October 11, 2017): 9819–27. https://doi.org/10.1523/JNEUROSCI.2053-17.2017.
Rosen SF, Ham B, Drouin S, Boachie N, Chabot-Dore A-J, Austin J-S, et al. T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice. J Neurosci. 2017 Oct 11;37(41):9819–27.
Rosen, Sarah F., et al. “T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice.J Neurosci, vol. 37, no. 41, Oct. 2017, pp. 9819–27. Pubmed, doi:10.1523/JNEUROSCI.2053-17.2017.
Rosen SF, Ham B, Drouin S, Boachie N, Chabot-Dore A-J, Austin J-S, Diatchenko L, Mogil JS. T-Cell Mediation of Pregnancy Analgesia Affecting Chronic Pain in Mice. J Neurosci. 2017 Oct 11;37(41):9819–9827.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

October 11, 2017

Volume

37

Issue

41

Start / End Page

9819 / 9827

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Receptors, Opioid, delta
  • Pregnancy, Animal
  • Pregnancy
  • Ovariectomy
  • Neurology & Neurosurgery
  • Neuralgia
  • Narcotic Antagonists
  • Naloxone
  • Microglia