Acute peripheral inflammation induces moderate glial activation and spinalIL-1 beta expression that correlates with pain behavior in the rat

Our laboratory has previously shown that glial activation and increased pro inflammatory cytokine expression are observed in the rat spinal cord follow ing peripheral nerve injuries that result in neuropathic pain behaviors. In the present study, we sought to determine whether acute peripheral inflamm ation induces changes in central glial and cytokine (Interleukin-1 beta) ex pression similar to those seen following peripheral spinal nerve transectio n. Two models of peripheral inflammation were used in this study: formalin (5% solution) or zymosan (25 mg/ml) injected subcutaneously into the planta r portion of the left hind paw of male Holtzman-strain Sprague-Dawley rats. The rats were euthanized at 1 h, 6 h, and 1, 3, 7 days post-injection (n = 4 or 5/group/time point). As expected, the animals treated with formalin s howed a spontaneous pain response and mechanical allodynia that persisted f or approximately 60 min following injection. The animals treated with zymos an exhibited mild spontaneous pain responses during the first hour and mech anical allodynia at 6 h and 1 day following injection. Immunohistochemistry for glial activation and cytokine expression was performed on L4-L5 spinal levels in all rats. Spinal sections from both formalin and zymosan treated animals exhibited microglial and astrocytic activation and increased Inter leukin-1 beta immunoreactivity at 1 and 6 h, respectively. Spinal glial act ivation and upregulation of Interleukin-1 beta appear to parallel the devel opment and maintenance of zymosan and formalin-induced mechanical allodynia . These findings support a unifying theory that glial activation and cytoki ne expression have a similar, if not related, role in producing hyperalgesi a following either peripheral inflammation or peripheral nerve injury. (C) 1999 Elsevier Science B.V. All rights reserved.