Abstract
BackgroundWe have previously reported that nerve injury-induced neuropathic pain is attenuated in toll-like receptor 2 (TLR2) knock-out mice. In these mice, inflammatory gene expression and spinal cord microglia actvation is compromised, whereas the effects in the dorsal root ganglia (DRG) have not been tested. In this study, we investigated the role of TLR2 in inflammatory responses in the DRG after peripheral nerve injury.ResultsL5 spinal nerve transection injury induced the expression of macrophage-attracting chemokines such as CCL2/MCP-1 and CCL3/MIP-1 and subsequent macrophage infiltration in the DRG of wild-type mice. In TLR2 knock-out mice, however, the induction of chemokine expression and macrophage infiltration following nerve injury were markedly reduced. Similarly, the induction of IL-1β and TNF-α expression in the DRG by spinal nerve injury was ameliorated in TLR2 knock-out mice. The reduced inflammatory response in the DRG was accompanied by attenuation of nerve injury-induced spontaneous pain hypersensitivity in TLR2 knock-out mice.ConclusionsOur data show that TLR2 contributes to nerve injury-induced proinflammatory chemokine/cytokine gene expression and macrophage infiltration in the DRG, which may have relevance in the reduced pain hypersensitivity in TLR2 knock-out mice after spinal nerve injury.
Highlights
We have previously reported that nerve injury-induced neuropathic pain is attenuated in toll-like receptor 2 (TLR2) knock-out mice
Macrophages infiltrate into the dorsal root ganglia (DRG) after peripheral nerve injury it has been reported that macrophages infiltrate into injured nerves and the DRG of rats after peripheral nerve injury [8], macrophage infiltration in mouse DRG after nerve injury has not been well characterized
TLR2 contributes to peripheral nerve injury-induced TNFa and IL-1b expression in the DRG and to the development of spontaneous pain behavior Previously, we reported that TLR2 contributes to pain hypersensitivity after L5 spinal nerve injury [20]
Summary
We have previously reported that nerve injury-induced neuropathic pain is attenuated in toll-like receptor 2 (TLR2) knock-out mice. In these mice, inflammatory gene expression and spinal cord microglia actvation is compromised, whereas the effects in the dorsal root ganglia (DRG) have not been tested. It has been suggested that TLR2, TLR3, and TLR4 play a role in the initiation of neuropathic pain through the recognition of host-derived endogenous ligands [19,20,21] Based on these reports, it was hypothesized that TLR endogenous ligands released from the damaged sensory neurons might activate spinal cord glial cells and thereby enhance pain hypersensitivity. We explored this hypothesis using TLR2 knock-out mice and found that TLR2 facilitates macrophage infiltration and pain-mediating proinflammatory gene expression in the DRG after spinal nerve injury
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