Open AccessA sensory subpopulation depends on vesicular glutamate transporter 2 for mechanical pain, and together with substance P, inflammatory pain
Author(s) -
Malin C. Lagerström,
Katarzyna Rogóż,
Bjarke Abrahamsen,
Anne-Li Lind,
Caroline Ölund,
Casey Smith,
José Alfredo Mendez,
Åsa Wallén-Mackenzie,
John N. Wood,
Klas Kullander
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1013602108
Subject(s) - substance p , hyperalgesia , nociceptor , sensory system , somatosensory system , neuroscience , mechanosensation , neuropathic pain , glutamate receptor , nociception , medicine , chronic pain , noxious stimulus , stimulus modality , neuropeptide , anesthesia , psychology , receptor , ion channel
Ablating or functionally compromising sets of sensory neurons has provided important insights into peripheral modality-specific wiring in the somatosensory system. Inflammatory hyperalgesia, cold pain, and noxious mechanosensation have all been shown to depend upon Nav 1.8-positive sensory neurons. The release of fast-acting neurotransmitters, such as glutamate, and more slowly released neuropeptides, such as substance P (SP), contribute to the diversified responses to external stimuli. Here we show that deletingVglut2 inNav 1.8Cre -positive neurons compromised mechanical pain and NGF-induced thermal hyperalgesia, whereas tactile-evoked sensation, thermal, formalin-evoked, and chronic neuropathic pain were normal. However, whenVglut2f/f ;Nav 1.8Cre mice were injected with a SP antagonist before the formalin test, the second phase pain response was nearly completely abolished, whereas in control mice, the pain response was unaffected. Our results suggest that VGLUT2-dependent signaling originating from Nav 1.8-positive neurons is a principal sensing mechanism for mechanical pain and, together with SP, inflammatory pain. These data define sets of primary afferents associated with specific modalities and provide useful genetic tools with which to analyze the pathways that are activated by functionally distinct neuronal populations and transmitters.