Contribution of nerve growth factor to augmented TRPV1 responses of muscle sensory neurons by femoral artery occlusion

Abstract

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.

Blockade of the TP receptor attenuates the exercise pressor reflex in decerebrated rats with chronic femoral artery occlusion

“…We speculate that, in part, these exaggerated pressor effects evoked in the 72-h-ligated rats were caused by an increase in nerve growth factor (NGF) whose levels in dorsal root ganglion cells were increased by femoral artery ligation (46). Support for our speculation comes from the finding that infusion of NGF by osmotic minipump was shown to increase the responsiveness of dorsal root ganglion cells to capsaicin (46).…”

“…In addition, static contraction of the hindlimb muscles in rats whose femoral arteries were ligated evoked a larger pressor reflex than did static contraction of the hindlimb muscles in rats whose hindlimbs were freely perfused (44). We speculate that, in part, these exaggerated pressor effects evoked in the 72-h-ligated rats were caused by an increase in nerve growth factor (NGF) whose levels in dorsal root ganglion cells were increased by femoral artery ligation (46). Support for our speculation comes from the finding that infusion of NGF by osmotic minipump was shown to increase the responsiveness of dorsal root ganglion cells to capsaicin (46).…”

Bradykinin B2 receptor contributes to the exaggerated muscle mechanoreflex in rats with femoral artery occlusion

“…Recent findings have suggested that femoral artery occlusion augments responsiveness of SNA and BP to stimulation of muscle mechanoand metabosensitive afferents (28,29,31,53,55,58,60,61). Muscle stretch used in the present experiment is considered to mainly stimulate muscle mechanoreceptors.…”

“…Under inhalation of an isoflurane-oxygen mixture (2-5% isoflurane in 100% oxygen), the surgical procedures were performed in 54 male Sprague-Dawley rats (6 to 8 wk old) as previously described (28,58,61). For the Western blotting experiments, femoral arteries of the right hindlimb of 12 rats were surgically exposed, dissected, and ligated ϳ3 mm distal to the inguinal ligament; this served as ligated limb.…”

“…Also, nerve growth factor (NGF) played a role in regulating expression of kinin B 2 receptor (41) and the levels of NGF were significantly increased in the DRG tissues 24 h after femoral artery ligation. However, there were no significant differences in increased NGF between 24 and 48 h after ligation (61). Thus 24 h of ligation was selected for the experiments in this report.…”