Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.
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Smith, E. S. J., Brand, A., Lewin, G., & Park, T. (2010). Functional neurokinin and NMDA receptor activity in an animal naturally lacking substance P: the naked mole-rat.. PLoS One, 5 e15162-e15162. https://doi.org/10.1371/journal.pone.0015162
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.
This work was supported by National Science Foundation grant 0744979, Sonderforschungsbereich 665, and the Alexander von Humboldt Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
External DOI: https://doi.org/10.1371/journal.pone.0015162
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266003
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/