Neuropathic pain from an experimental neuritis of the rat sciatic nerve

Painful peripheral neuropathies involve both axonal damage and an inflammat ion of the nerve. The role of the latter by itself was investigated by prod ucing an experimental neuritis in the rat. The sciatic nerves were exposed at mid-thigh level and wrapped loosely in hemostatic oxidized cellulose (Ox ycel(TM)) that on one side was saturated with an inflammatory stimulus, car rageenan (CARRA) or complete Found's adjuvant (CFA), and on the other side saturated with saline. In other rats, a myositis was created by implanting Oxycel saturated with CFA into a pocket made in the biceps femoris at a pos ition adjacent to where the nerve was treated. Pain-evoked responses from t he plantar hind paws were tested before treatment and daily thereafter. Sta tistically significant heat- and mechano-hyperalgesia, and mechano- and col d-allodynia were present on the side of the inflamed nerve (CARRA or CFA) f or 1-5 days after which responses returned to normal. There were no abnorma l pain responses on the side of the saline-treated nerve, and none in the r ats with the experimental myositis. The abnormal pain responses were inhibi ted by N-methyl-D-aspartate receptor blockade with MK-801, but were relativ ely resistant to the dose of morphine tested (10 mg/kg). Light microscopic examination of CARRA-treated nerves, harvested at the time of peak symptom severity, revealed that the treated region was mildly edematous and that th ere was an obvious endoneurial infiltration of immune cells (granulocytes a nd lymphocytes). There was either a complete absence of degeneration, or th e degeneration of no more than a few tens of axons. Immunocytochemical stai ning for CD4 and CD8 T-lymphocyte markers revealed that both cell types wer e present in the epineurial and endoneurial compartments. The endoneurial T -cells appeared to derive from the endoneurial vasculature, rather than fro m migration across the nerve sheath. We conclude that a focal inflammation of the sciatic nerve produces neuropa thic pain sensations in a distant region (the ipsilateral hind paw) and tha t this is not due to axonal damage. The neuropathic pain is specific to inf lammation of the nerve because it was absent in animals with the experiment al myositis and in those receiving sham-treatment. These results suggest th at an acute episode of neuritis-evoked neuropathic pain may contribute to t he genesis of chronically painful peripheral neuropathies, and that a chron ic (or chronically recurrent) focal neuritis might produce neuropathic pain in the absence of significant (or clinically detectable) structural damage to the nerve. The model that we describe is likely to be useful in the stu dy of the neuroimmune factors that contribute to painful peripheral neuropa thies. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V.