Resiniferatoxin (RTX) Causes a Uniquely Protracted Musculoskeletal Hyperalgesia in Mice by Activation of TRPV1 Receptors

JOURNAL OF PAIN

卷:14

Article

Abdelhamid, Ramy E.¹  Kovacs, Katalin J.¹  Honda, Christopher N.²  Nunez, Myra G.¹  Larson, Alice A.¹ 

[1] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA

[2] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55108 USA

关键词: Capsaicin;    pain;    musculoskeletal hyperalgesia;    desensitization;    nociception;   

DOI  :  10.1016/j.jpain.2013.07.021

来源: Elsevier

【 摘 要 】

Inactivation of transient receptor potential vanilloid-1 (TRPV1) receptors is one approach to analgesic drug development. However, TRPV1 receptors exert different effects on each modality of pain. Because muscle pain is clinically important, we compared the effect of TRPV1 ligands on musculoskeletal nociception to that on thermal and tactile nociception. Injected parenterally, capsaicin had no effect on von Frey fiber responses (tactile) but induced a transient hypothermia and hyperalgesia in both the tail flick (thermal) and grip force (musculoskeletal) assays, presumably by its agonistic action at TRPV1 sites. In contrast, resiniferatoxin (RTX) produced a chronic (>58 days) thermal antinociception, consistent with its reported ability to desensitize TRPV1 sites. In the same mice, RTX produced a transient hypothermia (7 hours) and a protracted (28-day) musculoskeletal hyperalgesia in spite of a 35.5% reduction in TRPV1 receptor immunoreactivity in muscle afferents. Once musculoskeletal hyperalgesia subsided, mice were tolerant to the hyperalgesic effects of either capsaicin or RTX whereas tolerance to hypothermia did not develop until after 3 injections. Musculoskeletal hyperalgesia was prevented but not reversed by SB-366791, a TRPV1 antagonist, indicating that TRPV1 receptors initiate but do not maintain hyperalgesia. Injected intrathecally, RTX produced only a brief musculoskeletal hyperalgesia (2 days), after which mice were tolerant to this effect. (C) 2013 by the American Pain Society

【 授权许可】

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