Effects of perineurally applied cytostatic, cytotoxic and chelating agents upon peripheral and central processes of primary nociceptive neurons.

After perineural application, the effects of mannomustine, cyclophosphamide, tetrameskylmannite, 6-mercaptopurine, azathioprine and d-penicillamine upon structure of peripheral nerves and the substantia gelatinosa Rolandi were studied by means of neurohistochemical techniques and compared to those of the microtubule inhibitors Vinblastine, Vincristine and colchicine. While the cytostatic and cytotoxic drugs induced only sporadic degeneration in the structure of the peripheral nerve and, accordingly, caused only a minor extent of transganglionic degenerative atrophy in the Rolando substance, the chelating agent d-penicillamine causes massive Wallerian degeneration after perineural application and, consequently, induces an extensive degenerative atrophy in the Rolando substance. The destructive effect of d-penicillamine upon conduction properties of the impaired nerve has been established also by means of electrophysiological recording. All the drugs studied differ fundamentally from microtubule inhibitors like the Vinca alcaloids that, by virtue of their blocking effect of axoplasmic transport, induce degenerative atrophy in the Rolando substance after perineural application without causing Wallerian degeneration in the peripheral nerve. Accordingly Vinca alcaloids are the most promising candidates as locally applied therapeutics in intractable pain.