Contribution of nerve growth factor to augmented TRPV1 responses of muscle sensory neurons by femoral artery occlusion.
In rats, hindlimb muscle ischemia induced by femoral artery occlusion augments the sympathetic nervous response to stimulation of transient receptor potential vanilloid type 1 (TRPV1) by injection of capsaicin into the arterial blood supply of the hindlimb muscles. The enhanced sympathetic response is due to alterations in TRPV1 receptor expression and its responsiveness in sensory neurons. The underlying mechanism by which TRPV1 receptor responses are increased after muscle vascular insufficiency/ischemia is unclear. In this report we tested the hypothesis that muscle ischemia elevates nerve growth factor (NGF) levels in primary afferent neurons, thereby increasing TRPV1 responsiveness. Muscle vascular insufficiency induced by the femoral artery ligation significantly increased NGF in the dorsal root ganglion (DRG) compared with sham controls. Furthermore, when NGF was infused in the hindlimb muscles of healthy rats (72 h using an osmotic minipump), the magnitude of the DRG neuron response to capsaicin was augmented (5.4 +/- 0.54 nA with NGF infusion vs. 3.0 +/- 0.17 nA in control; P < 0.05). With the addition of NGF in the culture dish containing the DRG neurons, the magnitude of the DRG neuron response to capsaicin was greater (6.4 +/- 0.27 nA; P < 0.05 vs. control) than that seen in control (2.9 +/- 0.16 nA). Note that 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. These data suggest that NGF affects a selective subpopulation of the afferent neurons in mediating augmented TRPV1 responses after femoral artery occlusion.
Xing
Jihong
J
Heart and Vascular Institute and Dept. of Medicine, Pennsylvania State Univ. College of Medicine, Milton S. Hershey Medical Center, 500 Univ. Dr., Hershey, PA 17033, USA.
Lu
Jian
J
Li
Jianhua
J
D000200:Action Potentials; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005263:Femoral Artery / Q000601:surgery; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D015918:Infusion Pumps, Implantable; D007511:Ischemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D037102:Lectins / Q000378:metabolism; D008026:Ligation; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000294:innervation*; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D037102:Lectins; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D020932:Nerve Growth Factor; D002211:Capsaicin