Evidence for the interaction of glutamate and NK1 receptors in the periphery

Susan M. Carlton, Shengtai Zhou, Richard E. Coggeshall

    Research output: Contribution to journalArticlepeer-review

    119 Scopus citations


    It is known that Substance P (SP) enhances glutamate- and N-methyl-D- aspartate (NMDA)-induced activity in spinal cord dorsal horn neurons and that this enhancement is important in the generation of wind-up and central sensitization. It is now known that SP and glutamate receptors are present on sensory axons in rat glabrous skin. This raises the issue as to whether SP and glutamate interact in the periphery. Using the tail skin in rats, the present study demonstrates 1) that unmyelinated axons at the dermal- epidermal junction immunostain for antibodies directed against NMDA, non- NMDA or SP (NK1) receptors; 2) that glutamate injected into the tail skin results in dose-dependent nociceptive behaviors interpreted as mechanical hyperalgesia, mechanical allodynia and thermal hyperalgesia, which are blocked following co-injection with glutamate antagonists; 3) that peripheral injection of SP potentiates glutamate-induced nociceptive behaviors in that the co-injection of SP + glutamate results in a significantly longer duration of behavioral responses compared to the responses seen following injection of either substance alone. These data provide support for the hypothesis that primary afferent neurons might well be subject to similar mechanisms that result in wind-up or central sensitization of spinal cord neurons.

    Original languageEnglish (US)
    Pages (from-to)160-169
    Number of pages10
    JournalBrain Research
    Issue number1-2
    StatePublished - Apr 20 1998


    • Mechanical allodynia
    • Mechanical hyperalgesia
    • NMDA
    • Non- NMDA
    • Spontaneous pain
    • Substance P

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • Clinical Neurology
    • Developmental Biology


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