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Contribution of nerve growth factor to augmented TRPV1 responses of muscle sensory neurons by hindlimb ischemia
Author(s) -
Xing Jihong,
Lu Jian,
Sinoway Lawrence,
Li Jianhua
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.611.1
Subject(s) - trpv1 , hindlimb , dorsal root ganglion , nerve growth factor , medicine , endocrinology , ischemia , reflex , substance p , femoral artery , capsaicin , nociception , transient receptor potential channel , anesthesia , receptor , anatomy , neuropeptide , dorsum
When metabolite‐sensitive transient receptor potential vanilloid type 1 (TRPV1) receptors are stimulated a reflex is engaged that increases sympathetic nerve activity. In rats, hindlimb ischemia enhances this response. The underlying mechanism by which TRPV1 receptor responses are increased after ischemic insult is unclear. In this experiment we tested the hypothesis that muscle ischemia/vascular insufficiency elevates nerve growth factor (NGF) levels in primary afferent neurons and thereby increasing TRPV1 responsiveness. Hindlimb muscle ischemia/vascular insufficiency induced by the femoral artery ligation significantly increased NGF in the dorsal root ganglion (DRG) as compared with sham‐controls. Furthermore, when NGF was infused into hindlimb muscles of healthy rats (72 hours using an osmotic minipump), the magnitude of the DRG neuron TRPV1 response increased (5.4±0.54 nA with NGF infusion vs. 2.5±0.55 nA in control, P <0.05). After adding NGF, the magnitude of the DRG neuron TRPV1 response induced by capsaicin was greater (5.5±0.33 nA, P <0.05 vs. control) than that seen in controls (2.2±0.37 nA). This NGF effect was seen in isolectin B 4 ‐negative DRG neurons, a group of thin fiber nerves that contain neuropeptides, and depend on NGF for survival. Thus NGF plays an important role in augmented TRPV1 responses after femoral artery occlusion. (All procedures outlined in this study were performed in compliance with the rules and regulations described in the NIH Guide for the Care and Use of Laboratory Animals ).