The perineurium modifies the effects of phenol and glycerol in rat sciatic nerve

Endoneurial cell response and type of nerve fibre damage were studied after perineural injections of 7% phenol-aqua and pure glycerol. Our previous studies have shown that phenol and glycerol induce different types of nerve fibre degeneration after intraneural injections: phenol dissolves axons and Schwann cells inside the basal lamina tubes but glycerol breaks them down into cellular flakes. The current study investigated whether the difference in type of endoneurial damage also appears after perineural application and how the perineurium affects the effect of these neurolytic agents. Rat sciatic nerves were treated with perineural injections of 7% phenol-aqua or pure glycerol and were followed up to 6 months. The results support the previous findings that perineural phenol injection induces damage that covers almost the whole endoneurium, but glycerol injection results in minor subperineurial damage. An ultrastructural study showed that the endoneurial effects are much milder after perineural injection than after intraneural injections. Phenol-induced nerve fibre dissolving was only rarely seen and the nerve fibre damage appeared similar to that after regular Wallerian degeneration in both groups. Axonal regeneration began within 2 weeks of the injections. Endoneurial macrophages were numerous in the damaged area in many individual nerves even at 3-6 months in both groups, which may indicate impaired phagocytotic activity. Regenerating axonal sprouts were seen first at 1 week post injection and Schwann cells proliferated within 2 weeks in both groups. However, the number of axonal sprouts was higher (P=0.002) and the size of the sprouts appeared larger after glycerol injection at 4 weeks post injection. The present study shows that the effects of extraneurally applied neurolytic agents phenol and glycerol are modified by the perineurium. Phenol readily penetrates the perineurium, but glycerol causes only subperineurial damage. The type of damage is rather similar to regular Wallerian degeneration in both groups and the endoneurial effects differ from those seen after intraneural injections.