Upregulation of TNFa and IL-6 in both the ipsilateral and contralateral dorsal root ganglia associated and non-associated with unilateral nerve injury: A possible role for intrathecal signaling
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| Year of publication | 2012 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Following mechanical injury to a peripheral nerve, Wallerian degeneration is an essential stimulus for inducing the cellular and molecular changes that underlie neuropathic pain. Compelling data suggest that hyperalgesia, allodynia and ongoing pain due to peripheral nerve injury are associated with neuroinflammation in the dorsal root ganglia (DRG), which is characterized by an upregulation of pro- and anti-inflammatory cytokines. Unilateral chronic constriction injury (CCI) of the sciatic nerve was performed aseptically in sixty-four rats. Neuropathic pain was measured as the withdrawal thresholds of mechanoallodynia and thermal hyperalgesia. On post-CCI days 1, 3, 7 and 14, expression of TNFa and IL-6 was measured bilaterally in the lumbar (L4-L5) and cervical (C7-C8) DRG using immunohistochemistry, western blot analysis, ELISA and in situ hybridization. In addition, the tracers FluoroRuby and FluoroEmerald were injected intrathecally at the level of lumbar or cervical spinal segments. Although mechanoallodynia and thermal hyperalgesia were detected predominantly in the ipsilateral hind paws, the expression of cytokines was enhanced in both the ipsilateral and contralateral cervical and lumbar DRG. The fluorescent tracers diffused from the intrathecal space into the DRG at the injection site as well as remote spinal segments. Our results indicate that cytokines are upregulated bilaterally both in the DRG of the spinal segments that are associated with the injured nerve and in the DRG of remote segments. Therefore, cerebrospinal fluid in the spinal intrathecal space is a putative pathway for signaling molecules to induce changes in proinflammatory cytokines in remote DRG. In conclusion, the upregulation of TNFa and IL-6 in the DRG non-associated with injured nerve suggests that neuroinflammation per se is not correlated strictly with neuropathic pain and is likely a manifestation of general preconditioning to the nervous tissue injury. |
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