Sciatic inflammatory neuritis ⟨SIN⟩:: Behavioral allodynia is paralleled by peri-sciatic proinflammatory cytokine and superoxide production

We have recently developed a model of sciatic inflammatory neuritis (SIN) to assess how immune activation near peripheral nerves influences somatosensory processing. Administration of zymosan (yeast cell walls) around a single sciatic nerve produces dose-dependent low-threshold mechanical allodynia without thermal hyperalgesia. Low (4 mug) doses produce both territorial and extraterritorial allodynia restricted to the injected hindleg. In contrast, higher (40 mug) doses produce territorial and extraterritorial allodynias of both hindlegs, an effect not accounted for by systemic spread of the zymosan, The aim of these experiments was to determine whether these behavioral allodynias were correlated with immunological and/or anatomical changes in or around the sciatic nerve, These experiments reveal that zymosan-induced bilateral allodynia was associated with the following: (a) increased release of both interleukin-1 beta and tumor necrosis factor-alpha from peri-sciatic immune cells; (b) increased release of reactive oxygen species from peri-sciatic immune cells; (c) no change in circulating levels of proinflammatory cytokine; (d) no apparent zymosan-induced influx of immune cells into the sciatic nerve from the endoneurial blood vessels; (e) mild edema of the sciatic, which was predominantly restricted to superficial regions closest to the peri-sciatic immune cells; and (f) no anatomic evidence of changes in either the ipsilateral saphenous nerve or contralateral sciatic nerve that could account for the appearance of extraterritorial or contralateral ("mirror") allodynia, respectively. No reliable differences were found when the low-dose zymosan was compared with vehicle controls. Taken together, these data suggest that substances released by peri-sciatic immune cells may induce changes in the sciatic nerve, leading to the appearance of bilateral allodynia.