Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli

被引:529
作者
Cavanaugh, Daniel J. [1 ]
Lee, Hyosang [2 ,3 ]
Lo, Liching [2 ,3 ]
Shields, Shannon D. [1 ]
Zylka, Mark J. [4 ]
Basbaum, Allan I. [1 ]
Anderson, David J. [2 ,3 ]
机构
[1] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94158 USA
[2] CALTECH, Div Biol, Pasadena, CA 91125 USA
[3] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA
[4] Univ N Carolina, Dept Cellular & Mol Physiol, Chapel Hill, NC 27599 USA
基金
美国国家卫生研究院;
关键词
Mrgprd; nociception; TRPV1; PRIMARY AFFERENT NEURONS; CAPSAICIN-RECEPTOR HOMOLOG; SUBSTANCE-P; VANILLOID RECEPTOR; PAIN PATHWAY; MICE LACKING; SPINAL-CORD; NOCICEPTORS; RAT; CHANNEL;
D O I
10.1073/pnas.0901507106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Behavioral responses to painful stimuli require peripheral sensory neurons called nociceptors. Electrophysiological studies show that most C-fiber nociceptors are polymodal (i. e., respond to multiple noxious stimulus modalities, such as mechanical and thermal); nevertheless, these stimuli are perceived as distinct. Therefore, it is believed that discrimination among these modalities only occurs at spinal or supraspinal levels of processing. Here, we provide evidence to the contrary. Genetic ablation in adulthood of unmyelinated sensory neurons expressing the G protein-coupled receptor Mrgprd reduces behavioral sensitivity to noxious mechanical stimuli but not to heat or cold stimuli. Conversely, pharmacological ablation of the central branches of TRPV1(+) nociceptors, which constitute a nonoverlapping population, selectively abolishes noxious heat pain sensitivity. Combined elimination of both populations yielded an additive phenotype with no additional behavioral deficits, ruling out a redundant contribution of these populations to heat and mechanical pain sensitivity. This double-dissociation suggests that the brain can distinguish different noxious stimulus modalities from the earliest stages of sensory processing.
引用
收藏
页码:9075 / 9080
页数:6
相关论文
共 42 条
  • [1] The cell and molecular basis of mechanical, cold, and inflammatory pain
    Abrahamsen, Bjarke
    Zhao, Jing
    Asante, Curtis O.
    Cendan, Cruz Miguel
    Marsh, Steve
    Martinez-Barbera, Juan Pedro
    Nassar, Mohammed A.
    Dickenson, Anthony H.
    Wood, John N.
    [J]. SCIENCE, 2008, 321 (5889) : 702 - 705
  • [2] The menthol receptor TRPM8 is the principal detector of environmental cold
    Bautista, Diana M.
    Siemens, Jan
    Glazer, Joshua M.
    Tsuruda, Pamela R.
    Basbaum, Allan I.
    Stucky, Cheryl L.
    Jordt, Sven-Eric
    Julius, David
    [J]. NATURE, 2007, 448 (7150) : 204 - 208
  • [3] TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents
    Bautista, DM
    Jordt, SE
    Nikai, T
    Tsuruda, PR
    Read, AJ
    Poblete, J
    Yamoah, EN
    Basbaum, AI
    Julius, D
    [J]. CELL, 2006, 124 (06) : 1269 - 1282
  • [4] Binshtok AM, 2007, NATURE, V449, P607, DOI 10.1038/nature06191
  • [5] Parallel "pain" pathways arise from subpopulation of primary afferent nociceptor
    Braz, JM
    Nassar, MA
    Wood, JN
    Basbaum, AI
    [J]. NEURON, 2005, 47 (06) : 787 - 793
  • [6] Response properties of mechanoreceptors and nociceptors in mouse glabrous skin: an in vivo study
    Cain, DM
    Khasabov, SG
    Simone, DA
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 2001, 85 (04) : 1561 - 1574
  • [7] The vanilloid receptor: A molecular gateway to the pain pathway
    Caterina, MJ
    Julius, D
    [J]. ANNUAL REVIEW OF NEUROSCIENCE, 2001, 24 : 487 - 517
  • [8] Impaired nociception and pain sensation in mice lacking the capsaicin receptor
    Caterina, MJ
    Leffler, A
    Malmberg, AB
    Martin, WJ
    Trafton, J
    Petersen-Zeitz, KR
    Koltzenburg, M
    Basbaum, AI
    Julius, D
    [J]. SCIENCE, 2000, 288 (5464) : 306 - 313
  • [9] The capsaicin receptor: a heat-activated ion channel in the pain pathway
    Caterina, MJ
    Schumacher, MA
    Tominaga, M
    Rosen, TA
    Levine, JD
    Julius, D
    [J]. NATURE, 1997, 389 (6653) : 816 - 824
  • [10] Vanilloid receptors take a TRP beyond the sensory afferent
    Caterina, MJ
    [J]. PAIN, 2003, 105 (1-2) : 5 - 9