Intrathecal anti-IL-6 antibody and IgG attenuates peripheral nerve injury-induced mechanical allodynia in the rat: possible immune modulation in neuropathic pain

Interleukin-6 (IL-6) is a pleiotrophic cytokine with a diverse range of act ions including the modulation of the peripheral and central nervous system. We have previously shown significant IL-6 protein and messenger RNA elevat ion in rat spinal cord following peripheral nerve injury that results in pa in behaviors suggestive of neuropathic pain. These spinal IL-6 levels corre lated directly with the mechanical allodynia intensity following nerve inju ry. In the current study, we sought to determine whether it is possible to attenuate mechanical allodynia and/or alter spinal glial activation resulti ng from peripheral nerve injury by specific manipulation of IL-6 with neutr alizing antibodies or by global immune modulation utilizing immunogamma-glo bulin (IgG). Effects of peripheral administration of normal goat IgG and in trathecal (i.t.) administration of IL-6 neutralizing antibody, normal goat or normal rat IgG on mechanical allodynia associated with L5 spinal nerve t ransection were compared. Spinal glial activation was assessed at day 10 po st surgery by immunohistochemistry. Low dose (0.01-0.001 mug) goal anti-rat IL-6 i.t. administration (P=0.025) significantly decreased allodynia and t rended towards significance at the higher dose (0.08 mug to 0.008 mug, P=0. 062). Low doses (0.01-0.001 mug) i.t. normal goat and rat IgG significantly attenuated mechanical allodynia, but not at higher doses (0.08-0.008 mug; P=0.001 for both goat and rat IgG). Peripherally administered normal goat I gG (30 or 100 mg/kg) did not attenuate mechanical allodynia. Spinal glial a ctivation was unaltered by any treatment. These data provide further eviden ce for the role of central IL-6 and neuroimmune modulation in the etiology of mechanical allodynia following peripheral nerve injury. (C) 2000 Elsevie r Science B.V. All rights reserved.