Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury

Inflammatory mechanisms are believed to play an important role in hyperalge sia resulting from nerve injury. Hyperalgesia following nerve injury is tem porally linked with Wallerian degeneration and macrophage recruitment, and is reduced in WLD mice, in which Wallerian degeneration is delayed. We soug ht more direct evidence that macrophages contribute to hyperalgesia and Wal lerian degeneration by depleting macrophages with liposomes loaded with dic hloromethylene diphosphonate (clodronate, Cl2MDP). Rats were subjected to p artial ligation of the sciatic nerve. Intravenous injection of liposome-enc apsulated clodronate reduced the number of macrophages in the injured nerve , alleviated thermal hyperalgesia and protected both myelinated and unmyeli nated fibres against degeneration. The results confirm the role of circulat ing monocytes/macrophages in the development of neuropathic hyperalgesia an d Wallerian degeneration due to partial nerve injury. Macrophage depletion immediately after nerve injury could have some clinical potential in preven tion of neuropathic pain. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.