Possible role of inflammatory mediators in tactile hypersensitivity in ratmodels of mononeuropathy

Peripheral hypersensitivity (hyperalgesia and allodynia) are common phenome na both in inflammatory and in neuropathic pain conditions. Several rat mod els of mononeuropathy (Bennett, Seltzer and Gazelius models) display such s ymptoms following partial injury to the sciatic nerve. Using immunohistoche mistry and behavioral tests, we investigated inflammatory cell and cytokine responses in the sciatic nerve 14 days after injury created in these diffe rent models as well as after axotomy. Tactile hypersensitivity ('allodynia' ) was present in all Gazelius model rats whereas only 38 and 29% of the Ben nett and Seltzer models, respectively, displayed this-sign of neuropathy. T he inflammatory reactions in rats with and without tactile allodynia were c ompared. Monocytes/macrophages (ED-1), natural killer cells, T lymphocytes, and the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), were significantly upregulated in all nerve inju red rats in comparison to sham-operated controls. Interestingly, ED-1-, TNF -alpha- and IL-6-positive cells increased more markedly in allodynic Bennet t and Seltzer rats than in non-allodynic ones. The magnitude of the inflamm atory response does not seem to relate to the extent of damage to the nerve fibers because axotomized rats displayed much lower upregulation. Our find ings indicate that the considerable increase in monocytes/macrophages induc ed by a nerve injury results in a very high release of IL-6 and TNF-alpha. This may relate to the generation of tactile allodynia/hyperalgesia, since there was a clear correlation between the number of ED-1 and IL-6-positive cells and the degree of allodynia. It is possible that measures to reduce m onocyte/macrophage recruitment and the release of pro-inflammatory interleu kins after nerve damage could influence the development of neuropathic pain . (C) 2000 International Association for the Study of Pain. Published by El sevier Science B.V. All rights reserved.