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) t o assess how immune activation near peripheral nerves influences somatosens ory processing. Administration of zymosan (yeast cell walls) around a singl e sciatic nerve produces dose-dependent low-threshold mechanical allodynia without thermal hyperalgesia. Low (4 mug) doses produce both territorial an d extraterritorial allodynia restricted to the injected hindleg. In contras t, higher (40 mug) doses produce territorial and extraterritorial allodynia s of both hindlegs, an effect not accounted for by systemic spread of the z ymosan, The aim of these experiments was to determine whether these behavio ral allodynias were correlated with immunological and/or anatomical changes in or around the sciatic nerve, These experiments reveal that zymosan-indu ced bilateral allodynia was associated with the following: (a) increased re lease 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 proinfla mmatory cytokine; (d) no apparent zymosan-induced influx of immune cells in to the sciatic nerve from the endoneurial blood vessels; (e) mild edema of the sciatic, which was predominantly restricted to superficial regions clos est to the peri-sciatic immune cells; and (f) no anatomic evidence of chang es 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 whe n the low-dose zymosan was compared with vehicle controls. Taken together, these data suggest that substances released by peri-sciatic immune cells ma y induce changes in the sciatic nerve, leading to the appearance of bilater al allodynia.