Molecular Expression in Dorsal Root Ganglia of Neuropathic Pain Mice Induced by Spared Nerve Injury
Date Issued
2015
Date
2015
Author(s)
Chen, Ching-Yu
Abstract
Neuropathic pain refers to pains resulting from disease or damage of the peripheral or central nervous systems, and from dysfunction of the nervous system. Patients suffer from this chronic, intensively painful experience that is difficult to treat with conventional analgesic medications. Peripheral nerve injury is one of the etiologies causing neuropathic pain, and ATP seems to be strongly implicated in peripheral pain sensitization. The purinergic receptor, P2X3, a ligand-gated cation channel, is expressed in a subset of small-diameter, primary afferent neurons, and might be a potential therapeutic target to relieve pain. Previous studies showed controversial results in terms of P2X3 expression in several peripheral nerve injury models. Some claimed that a functional up-regulation of P2X3 in dorsal root ganglia, whereas some reported contradicted results. We hope to investigate the regulation of P2X3 gene expression. Using spared nerve injury model (SNI) in mice, we found animals displayed mechanical allodynia in the spared sural territory one week after surgery and persisted at least two weeks. From the results of immunofluorescent staining to estimate the P2X3 (+) neuron ratio on lumbar (L4) dorsal root ganglia (DRG), P2X3 receptors were mainly expressed in small and medium sized neurons, while few percentages of large neurons were also discovered both in the contralateral and ipsilateral sides. The P2X3 immunoreactive neuron ratios between ipsilateral and contralateral DRG did not show significant difference, and the distribution were highly colocalized with the nonpeptidergic neurons that express IB4, but rarely co-expressed with CGRP immunoreactive neurons, which are peptidergic. The (IB4/P2X3) neuron ratios in ipsilateral DRG were statistically lower than the contralateral DRG, suggesting a morphological shift of P2X3 distribution could be happened. To screen the possible gene candidates regulating P2X3 expression on transcriptional level, we used bioimformatic web tools and further filtered by their functions. One possible molecule, activating transcription factor-3 (ATF3), was increased on the ipsilateral DRG significantly. Although the mechanical thresholds of ATF3-knockout mice after SNI were similar to those of the wild-type group, it is worth pursuing whether there exist relationship, probably with different neuropathic pain models. In our study of SNI mouse model with mechanical allodynia, inconsistency of the sham group in difference of mechanical thresholds compared to absolute values, comparison of sensory abnormalities between dynamic plantar aesthesiometer and manual von Frey filaments, pain behaviors in different neuropathic pain models and species are possible issues to be investigated. From the results of immunofluorescent staining, quantities of large sized neuron in P2X3 (+) populations, degrees and location of nerve injury, and distribution of injured and intact neurons in DRG after SNI are also required to be further clarified.
Subjects
Spared nerve injury(SNI)
Neuropathic pain
P2X3
Activating transcription factor-3(ATF3)
Dorsal root ganglion(DRG)
Nociceptor
Type
thesis
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