DISTRIBUTION AND AXONAL RELATIONS OF MACROPHAGES IN A NEUROMA

After axotomy in the peripheral nervous system, most axons regrow and re-establish contact with their targets. Depending on the type of lesi on, a varying number of nerve fibers fail to regenerate and terminate far from the target, forming a neuroma. Sensory axons trapped in a neu roma show abnormal sensitivity to various stimuli, and often fire spon taneously. In this study we have examined the distribution and axonal relations of macrophages in rat sciatic neuromas three days to one yea r after cutting and ligating the nerve. ED1-immunoreactive macrophages migrated into the neuroma in large numbers within the two first weeks after the injury. Most cells were at that time located 0.5-1 mm proxi mal to the ligature. From three weeks on, a majority of the ED1-immuno reactive cells contained numerous large vacuoles filled with myelin fr agments. At sites of focal demyelination, macrophages often had direct contact with axonal membranes. At later survival stages (three months to one year) ED1-immunoreactive cells were seen not only in the area just proximal to the ligature, but also several millimeters proximal t o this. Macrophages persisted in considerable numbers in the neuroma f or at least one year. These data suggest that neuroma macrophages may participate in the genesis of electrophysiological abnormalities thoug ht to underly chronic pain after neuroma formation, possibly by creati ng demyelinated axonal regions susceptible to external stimuli from e. g. neighboring nerve fibers, by releasing substances which influence r egeneration and remodelling of axonal growth cones, or by direct actio ns on the denuded axonal membranes.