Introduction
Results
Intravenous injection of paclitaxel induces acute pain in rodents
Low levels of paclitaxel are found in the CSF and spinal dorsal horn after paclitaxel injection and intrathecal injection of paclitaxel induces acute pain in rats
Activation of TLR4 in the spinal dorsal horn and dorsal root ganglions is critically implicated in paclitaxel-induced acute pain
Paclitaxel increases the release of glutamate from presynaptic terminals and the activity of glutamate receptors at postsynaptic neurons in the spinal dorsal horn
Frequencies and amplitudes of mEPSCs are increased by paclitaxel in spinal dorsal horn neurons through activation of TLR4
Dysfunction of glial glutamate transporters (GTs) contributes to the development of the paclitaxel-induced acute pain
Paclitaxel reduces glial glutamate transporter activities through activating TLR4
Discussion
Acute pain induced by paclitaxel treatment
Paclitaxel penetrating into the spinal dorsal horn is a critical event leading to the development of acute pain following paclitaxel injection
Paclitaxel induces acute pain through activating TLR4
Conclusions
Methods and materials
Animals
Drug administration
Behavioral tests
Measurements of mechanical thresholds of hind paw withdrawal responses
Burrowing behavior assessments
Measurements of paclitaxel concentrations in CSF and spinal dorsal horn using liquid chromatography tandem mass spectrometry
Spinal slice preparations, recording and analysis of miniature excitatory postsynaptic currents (mEPSCs) from neurons and glial glutamate transporter currents (GTCs) from astrocytes in the spinal dorsal horn
Spinal slice preparations
Recordings of mEPSCs
Recordings of glutamate transporter currents (GTCs)
In vitro measurement of glutamate uptake activity
Western blot experiments
Single-cell reverse transcription-PCR (RT-PCR)
GFAP (371 bp, 218 bp)a
| CAGAGCGAGCCTATGCTAAA | GCCTATGCTAAAGGTTAGGTTGTA | NM_001131020 |
CGTCCAGAGGGAACTAACTAAC | AGCACTGAAGTGAAGCAATAGA | ||
GAPDH (367 bp, 313 bp)a
| AGCCTCGTCCCGTAGACAAAA | TGAAGGTCGGTGTGAACGAATT | XM_001473623 |
TTTTGGCTCCACCCCTTCA | GCTTTCTCCATGGTGGTGAAGA |