RNA interference-mediated knock-down of transient receptor potential vanilloid 1 prevents forepaw inflammatory hyperalgesia in rat

Authors

  • Susumu Kasama,

    1. Department of Pathology, Shinshu University School of Medicine
    2. Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine
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  • Masatomo Kawakubo,

    1. Department of Pathology, Shinshu University School of Medicine
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    • *

      Present address: Department of Laboratory Medicine, Shinshu University Hospital, Asahi 3-1-1, Matsumoto 390-8621, Japan

  • Takefumi Suzuki,

    1. Department of Laboratory Medicine, Shinshu University Hospital
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  • Tomoko Nishizawa,

    1. Department of Pathology, Shinshu University School of Medicine
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  • Akiko Ishida,

    1. Department of Pathology, Shinshu University School of Medicine
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    • Present address: Department of Pathology, Hata General Hospital, 4417-180 Hata-machi, Higashichikuma-gun, Nagano 390-1401, Japan

  • Jun Nakayama

    1. Department of Pathology, Shinshu University School of Medicine
    2. Institute of Organ Transplants, Reconstructive Medicine and Tissue Engineering, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan
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Dr Jun Nakayama, Department of Pathology, Shinshu University School of Medicine, as above.
E-mail: jun@hsp.md.shinshu-u.ac.jp

Abstract

Transient receptor potential vanilloid (TRPV)1 is a ligand-gated cation channel expressed by primary sensory neurons, including those in the dorsal root ganglia (DRG). TRPV1 plays an essential role in development of inflammatory thermal hyperalgesia after tissue injury and its expression in rat lumbar DRG is increased after hindpaw inflammation. However, the identity of factors mediating forepaw inflammatory hyperalgesia has remained elusive. Here, we examined behavioral responses to noxious thermal stimuli after forepaw inflammation in rats and found that inflammation induced by intraplantar injection of complete Freund's adjuvant significantly reduced hot-plate latency (HPL) at 50 °C. TRPV1 expression levels in the ipsilateral cervical DRG were also elevated after forepaw inflammation. By contrast, HPL at 56 °C was not shortened after forepaw inflammation and expression of TRPV2, a TRPV1 homolog, in the DRG was not increased. Paratracheal injection of short interfering RNA targeting TRPV1 blocked TRPV1 up-regulation in cervical DRG and abolished inflammation-mediated HPL reductions seen at 50 °C. However, thermal hyperalgesia previously established by inflammation was not reversed by short interfering RNA injection. These results indicate that: (i) enhanced TRPV1 expression in cervical DRG is closely associated with development of inflammatory thermal hyperalgesia in the forepaw after tissue injury and (ii) RNA interference targeting TRPV1 prevents inflammatory thermal hyperalgesia after forepaw injuries but does not ameliorate it when already established in a rat model of nociceptive pain representing upper limb injury in humans.

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