Title: Neuroinflammatory reactions of the dorsal root ganglia afterunilateral peripheral nerve injury: a usefulness of in situproteomics
Abstract: Background and aims. The dorsal root ganglia (DRG) containing
the primary sensory neurons react intensely to various types of
nerve injury and play a key role in neuropathic
hypersensitivity. Recently, there has been considerable
interest in contribution of pro- and anti-inflammatory
cytokines in the induction and maintenance of neuropathic pain
derived from their changes predominantly in the DRG. Unilateral
chronic constriction injury (CCI) and spare nerve injury (SNI)
of the rat sciatic nerve are frequently used as experimental
models of neuropathic pain (NPP). The aim of the present study
was to investigate alterations of pro- and anti-inflammatory
cytokines in both ipsilateral and contralateral L4-L5 as well
as C7-C8 DRG in rat neuropathic pain models. Methods.
Unilateral CCI and SNI of the sciatic nerve were performed
aseptically in sixty rats. Neuropathic pain induction was
tested by measurement of mechanoallodynia and thermal
hyperalgesia. Expression of IL-1b, TNFa, IL-6, IL-10 and their
receptors were investigated bilaterally in lumbar (L4-5) and
cervical (C7-8) DRG by MicroELISA and immunohisto-chemistry 1,
3, 7 and 14 days after surgery. The double immunostaining with
GFAP or GS and ED1 was used to recognize satellite glial cells
and invaded macrophages, respectively. Results. Ipsilateral
hind paws of CCI/SNI rats displayed constant mechanoallodynia
and thermal hyperalgesia while contralateral hind paws and
forepaws of both sides exhibited inconstant hypersensitivity.
MicroELISA revealed that rats operated on unilateral CCI or SNI
display significant elevation of pro- and anti-inflammatory
cytokine levels not only in DRG associated but also
non-associated with injured nerve. Parallel immunohistochemical
staining (in situ proteomics) showed precise cellular
distribution of IL-1b, TNFa, IL-6, IL-10 and their receptors in
the bodies of primary sensory neurons, their satellite glial
cells and macrophages invading the DRG. The double
immunostaining with cellular markers enable us to specify a
contribution of the individual cellular populations to DRG
inflammatory reactions after nerve injury, and their possible
involvement in NPP induction. Conclusions. The results suggest
that up-regulation of pro- and anti-inflammatory cytokines and
their signaling is not only associated with neuropathic pain
induction. Neuroinflammatory reaction to neuropathic stress is
propagated alongside neuroaxis from lumbar to remote DRG
related probably with conditioning of the cervical DRG neurons
to injury.
Publication Year: 2013
Publication Date: 2013-01-01
Language: en
Type: article
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