Painful Peripheral Neuropathies and C-Fiber Nociceptors

摘要

Peripheral neuropathies are among the most prevalent disorders that cause neuropathic pain. An indication of the magnitude of the problem is seen in the number of individuals with either the painful neuropathy of diabetes or that associated with HIV/AIDS. This chapter focuses on a series of studies relevant to painful neuropathies that were performed in laboratories at Johns Hopkins University. The Hopkins studies were motivated by clinicopathological experience with painful "small-fiber" neuropathies (Holland et al. 1997, 1998; Periquet et al. 1999; Polydefkis et al. 2000), and by experimental investigations that were triggered by recent reports (Sato and Perl 1991; Koltzenburg et al. 1994; Myers et al. 1996; Wagner and Myers 1996; Ramer et al. 1997; Sorkin et al. 1997) suggesting that Wallerian degeneration might contribute to neuropathic pain. The four laboratories that joined in these studies are the cutaneous neurology laboratory, the neuromuscular service, and the peripheral nerve laboratories in the Department of Neurology, and the pain physiology laboratories in the Department of Neurosurgery. Encapsulating in a few sentences a single distinctive hypothesis from these studies is neither possible nor appropriate, given the relevant data that derive from many other laboratories, as well as the diversity of favored hypotheses and of interpretations of data among the Hopkins investigators. However, both our clinical and experimental studies share several perspectives. First, we are interested in the possibility that "spared," uninjured peripheral nerve fibers, as well as injured fibers, might contribute to the development of neuropathic pain. Second, we are asking to what extent physiological and structural changes in C-fiber nociceptors might contribute to neuropathic pain. Third, we are investigating to what extent Wallerian degeneration of neighboring nerve fibers might influence uninjured nociceptors in a fashion that favors development of neuropathic pain.