Publication details
Neuroinflammatory reactions of the dorsal root ganglia after unilateral peripheral nerve injury: a usefulness of in situ proteomics
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| Year of publication | 2013 |
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| Description | 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. |