Cellular distribution of TNF type 1 and type 2 receptor proteins in relation to upregulation of TNF-alpha in the dorsal root ganglia of rat neuropathic pain model
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| Year of publication | 2012 |
| Type | Conference abstract |
| MU Faculty or unit | |
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| Description | TNF-alpha is a principal immune mediator of the early degenerative changes in peripheral nerve injury contributing to both inflammatory and neuropathic hyperalgesia. TNF-alpha actions are mediated via two distinct receptor subtypes, constitutively expressed receptor-1 (TNFR1) and inducible receptor-2 (TNFR2). Unilateral chronic constriction (CCI) of the adult rat sciatic nerves were used as experimental model of neuropathic pain. In situ changes of TNF-alpha, TNFR1, TNFR2 proteins and their mRNAs in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) were investigated by immunofluorescence detection, ELISA, Western blot analysis and in situ hybridization. Very low levels of TNF-alpha, TNFR1, TNFR2 protein and their mRNAs were found in the neuronal bodies and satellite glial cells (SGC) of DRG from naive rats. Unilateral CCI of sciatic nerve induced a bilateral elevation of TNF-alpha and TNFR1 predominantly in the neuronal bodies of both lumbar and cervical DRG. The elevation of TNF-alpha, TNFR1 proteins and their mRNAs was confirmed by ELISA, WB as well as in situ hybridization. In contrast, TNFR2 was upregulated in small-sized neuronal bodies and mainly in SGC of DRG from rats operated on CCI. The DRG removed from sham-operated rats displayed moderate levels of TNF-alpha and TNFR1 immunostaining in the neuronal bodies, but with a higher intensity of TNFR2 in SGC. The results suggest that TNF-alpha is synthesized by both DRG neurons and SGC. However, neurons express TNFR1 that is activated by both soluble and membrane TNF-alpha, in contrast to TNFR2 in SGC activated only by membrane TNF-alpha. |
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