Limited role of macrophages in generation of nerve injury-induced mechanical allodynia

The purpose of this study was to investigate the role of peripheral macroph ages in the generation of mechanical allodynia utilizing a modification of the Chung rat model of neuropathy. Three distinct methods were used: (1) sy stemic and perineural macrophage inhibition utilizing CNI-1493; (2) depleti on of the peripheral macrophage population by liposome-encapsulated clodron ate: and (3) perineural administration of activated or inactivated bone mar row-derived macrophages (BMDM) in sham-surgery rats. Mechanical allodynia w as tested on days 1, 3, 5, 7, and 10 post-intervention or surgery using von Frey monofilaments. In order to assess the role of spinal glia following t hese interventions, microglial (CNS macrophages) and astrocytic activation was assessed using immunohistochemistry. CNI-1493 did not attenuate mechani cal allodynia, or spinal glial expression as compared to the saline control group. Similarly, the clodronate depletion of peripheral macrophages prior to nerve injury did not have any effect on the resultant mechanical allody nia or spinal glial activation. Perineural administration of activated or i nactivated BMDM did not evoke mechanical allodynia in sham surgery rats. Of interest, we observed an ipsilateral, dorsal horn increase in microglial e xpression following perineural administration of activated macrophages. In summary, these data suggest a limited role of activated macrophages in the onset of mechanical allodynia in an animal model of neuropathy. (C) 2000 El sevier Science Inc. All rights reserved.