Painful pathways induced by TLR stimulation of dorsal root ganglion neurons
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Updated: Jun 2, 2026

Patch Clamp Recordings on Intact Dorsal Root Ganglia from Adult Rats
Published on: September 29, 2016
Jia Qi1, Krisztina Buzas, Huiting Fan
1Laboratory of Molecular Immunoregulation, Cancer and Inflammatory Program, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
Abstract:
We hypothesize that innate immune signals from infectious organisms and/or injured tissues may activate peripheral neuronal pain signals. In this study, we demonstrated that TLRs 3, 7, and 9 are expressed by human dorsal root ganglion neurons (DRGNs) and in cultures of primary mouse DRGNs. Stimulation of murine DRGNs with TLR ligands induced expression and production of proinflammatory chemokines and cytokines CCL5 (RANTES), CXCL10 (IP-10), IL-1α, IL-1β, and PGE(2), which have previously been shown to augment pain. Further, TLR ligands upregulated the expression of a nociceptive receptor, transient receptor potential vanilloid type 1 (TRPV1), and enhanced calcium flux by TRPV1-expressing DRGNs. Using a tumor-induced temperature sensitivity model, we showed that in vivo administration of a TLR9 antagonist, known as a suppressive oligodeoxynucleotide, blocked tumor-induced temperature sensitivity. Taken together, these data indicate that stimulation of peripheral neurons by TLR ligands can induce nerve pain.
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