A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats

TLDR

Immune activation near healthy peripheral nerves may play a greater role in generating pathological pain than previously recognized, and because many clinical neuropathies arise from peripheral nerve inflammation rather than trauma, understanding this process could inform novel pain‑control strategies. The authors developed a new sciatic inflammatory neuritis model to assess how immune activation influences somatosensory processing. The model involves acute peri‑sciatic injection of zymosan into awake, unrestrained rats to induce inflammatory neuritis. Acute zymosan injection around the sciatic nerve rapidly induces low‑threshold mechanical allodynia within 3 h, with low doses producing ipsilateral allodynia and higher doses producing bilateral allodynia, and evidence suggests the contralateral allodynia arises from local nerve actions rather than systemic spread.

Abstract

Immune activation near healthy peripheral nerves may have a greater role in creating pathological pain than previously recognized. We have developed a new model of sciatic inflammatory neuritis to assess how such immune activation may influence somatosensory processing. The present series of experiments reveal that zymosan (yeast cell walls) acutely injected around the sciatic nerve of awake unrestrained rats rapidly (within 3 h) produces low threshold mechanical allodynia in the absence of thermal hyperalgesia. Low (4 μg) doses of zymosan produce both territorial and extra-territorial allodynia restricted to the ipsilateral hindpaw. Higher (40–400 μg) doses of zymosan again produce both territorial and extra-territorial allodynia. However, allodynia is now expressed both in the ipsilateral as well as contralateral hindpaws. Several lines of evidence are provided that the appearance of this contralateral (‘mirror’) allodynia reflects local actions of zymosan on the sciatic nerve rather than spread of this immune activator to the general circulation. Since many clinical neuropathies result from inflammation/infection of peripheral nerves rather than frank physical trauma, understanding how immune activation alters pain processing may suggest novel approaches to pain control.