T lymphocytes are increasingly implicated in pain signaling. A subset of T lymphocytes, termed TChAT, express the rate-limiting enzyme for...
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[title] => Cholinergic modulation is independent of T lymphocytes in a mouse model of neuro
[paragraph] => Cholinergic modulation is independent of T lymphocytes in a mouse model of neuropathic pain
[content] => Authors
K Halievski, AS Sengar, J Hicks et al
Lab
The Hospital for Sick Children, Toronto, ON, Canada
Journal
Molecular Pain
Abstract
T lymphocytes are increasingly implicated in pain signaling. A subset of T lymphocytes, termed TChAT, express the rate-limiting enzyme for acetylcholine (ACh) production, choline acetyltransferase (ChAT), and mediate numerous physiological functions. Given that cholinergic signaling has long been known to modulate pain processing and is the basis for several analgesics used clinically, we asked whether TChAT could be the intersection between T lymphocyte and cholinergic mediation of pain signaling. In this study, we used a mouse gene knockout strategy to ablate ChAT specifically from T lymphocytes and examined the development and expression of mechanical and thermal hypersensitivity in a spared nerve injury (SNI) mouse model of neuropathic pain. We found that mice with ChAT knockout in T cells (floxed Chat plus CD4-Cre recombinase) did not differ from control mice with intact ChAT (floxed Chat, but no Cre recombinase) in their expression of mechanical sensitivity before or after injury. Similarly, thermal sensitivity was unaffected after injury, with control mice expressing similar patterns of thermal preference to mice whose T cells do not express ChAT. Our experiments demonstrate that cholinergic signaling initiated by T lymphocytes neither dampens nor exacerbates the expression of mechanical or thermal sensitivity in neuropathic mice. Thus, while both cholinergic signaling and T lymphocytes have established roles in modulating pain phenotypes, it is not cholinergic signaling initiated by T lymphocytes that drive this. Our findings will help to narrow in on which aspects of T-cell modulation may prove useful as therapies.
BIOSEB Instruments Used
Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT)
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[name] => Thermal Place Preference- 2 Temperatures Choice Nociception Test
[description_short] => An operator independent test to study pain thresholds in rodents (mouse and rat) by assessing temperature preference (thermal comfort zone) - a new tool for your analgesia/nociception research opening new fields of investigation, and an ideal solution for nociceptive and analgesic drugs screening. Now comes with a brand new software, allowing tracking activity and faster temperature transitions!


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