Absence of Substance P and CGRP in the Dorsal Root Ganglia of Naked Mole Rats Correlates with an Absence of Hyperalgesia to Heat

摘要

Activation of nociceptive primary afferents induces the release of neu-rotransmitters, such as amino acids, substance P (SP), and calcitonin gene-related peptide (CGRP) (Yaksh 1988; Lawand et al. 2000; Yeomans et al. 2000). The neuropeptides SP and CGRP coexist in the same neurons in the dorsal root ganglia (DRG; Gulbenkian et al. 1986). They are expressed by primary afferent fibers and released from the central terminals in the spinal cord by the application of noxious stimuli, including capsaicin injection (Mantyh et al. 1995). SP appears to be released by activation of unmyeli-nated (C-fiber), but not of myelinated (AS-fiber), thermonociceptors (Zachariou et al. 1997). Intraspinal release of immunoreactive SP is evoked by electrical stimulation of unmyelinated C-afferent fibers in peripheral nerves and by thermal or mechanical noxious stimuli applied to the skin (Go and Yaksh 1987; Duggan et al. 1988, 1992; Collin et al. 1991). CGRP also increases the nociceptive flexion reflex mediated via C-afferent fibers in the spinal cord (Woolf and Wiesenfeld-Hallin 1986). Most of the CGRP-bind-ing sites were expressed in unmyelinated DRG neurons (Schaible et al. 2002). Thus, different nociceptor types make and release different ensembles of neurotransmitters (Lawson 1995). SP and CGRP are predominantly made and released by unmyelinated C-afferent nociceptors.