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Whether activation of primary sensory pathways can ever produce sufficient over\u2010activity in secondary sensory neurons in the dorsal horn of the spinal cord to induce cell death, however, has not been determined. In this study, we asked whether activity in myelinated afferents (A fibers), which use glutamate as a transmitter, can induce cell death in the dorsal horn. Using stereological estimates of neuron numbers from electron microscopic sections, we found that stimulation of A\u2010fibers in an intact sciatic nerve at 10 Hz, 20 Hz, and 50 Hz in 10\u2010minute intervals at a stimulus strength that activates both A\u03b2 and A\u03b4 fibers resulted in the loss of 25% of neurons in lamina III, the major site of termination of large A\u03b2 fibers, but not in lamina I, where A\u03b4 fibers terminate. Furthermore, sciatic nerve lesions did not result in detectable neuron loss, but activation of A fibers in a previously sectioned sciatic nerve did cause substantial cell death not only in lamina III but also in laminae I and II. The expansion of the territory of A\u2010fiber afferent\u2010evoked cell death is likely to reflect the sprouting of the fibers into these laminae after peripheral nerve injury. The data show, therefore, that primary afferent A\u2010fiber activity can cause neuronal cell death in the dorsal horn with an anatomical distribution that depends on whether intact or injured fibers are activated. Stimulation\u2010induced cell death potentially may contribute to the development of persistent pain. J. Comp. Neurol. 435:276\u2013282, 2001. \u00a9 2001 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/cne.1029","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T21:41:59Z","timestamp":1030311719000},"page":"276-282","source":"Crossref","is-referenced-by-count":49,"title":["A\u2010fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord"],"prefix":"10.1002","volume":"435","author":[{"given":"Richard E.","family":"Coggeshall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena A.","family":"Lekan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford 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