title: Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.
abstract: Naked mole-rats are extremely unusual among mammals in that their cutaneous C-fibers lack the neuropeptide Substance P (SP). In other mammals, SP plays an important role in nociception: it is released from C-fibers onto spinal neurons where it facilitates NMDA receptor activity and causes sensitization that can last for minutes, hours or days. In the present study, we tested the effects of intrathecal application of: 1) SP, 2) an SP antagonist (GR-82334), and 3) an NMDA antagonist (APV) on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate, and long-lasting sensitization of foot withdrawal latency that was transiently reversed by application of either antagonist. However, neither SP nor NMDA antagonists had an effect when administered alone to naïve animals. In contrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in naked mole-rats have functional SP and NMDA receptors, but that these receptors do not participate in heat-evoked foot withdrawal unless SP is experimentally introduced. We propose that the natural lack of SP in naked mole-rat C-fibers may have resulted during adaptation to living in a chronically high carbon dioxide, high ammonia environment that, in other mammals, would stimulate C-fibers and evoke nocifensive behavior.
authors.affiliation: Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors.forename: Antje
authors.initials: A
authors.lastname: Brand
authors.forename: Ewan St J
authors.initials: ES
authors.lastname: Smith
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Park
mesh_terms: D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D005502:Food; D007150:Immunohistochemistry / Q000379:methods; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019577:Mole Rats; D009412:Nerve Fibers / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013373:Substance P / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; D013373:Substance P