This study investigates the effects of antinerve growth factor (anti-NGF) application on isolated ileal contractility in the rat. For this purpose, rats were divided into four groups. The control animals (n=8) received only intraperitoneal injection of an isotonic NaCl solution (i.p). Anti-NGF was daily administered intraperitoneally at the dose of 1 ng/g level in the first experimental group (n=8), and at doses of 10 ng/g (n=7) and 40 ng/g (n=7) in the second and third experimental groups, respectively. Seven days after the injections rats were sacrificed and ileum segments were isolated. Responses to acetylcholine (ACh) were evaluated by using standard Tyrode, double-calcium Tyrode and
calcium-free Tyrode solutions. The average peak amplitude of ACh-induced contractions recorded in standard Tyrode solution was significantly decreased in all three experimental groups as compared to the control group (p<0.05). When double-calcium Tyrode solution was used as the perfusion medium, the responses to ACh were also lower in all anti-NGF applied groups as compared to its control group (p<0.05). Our results showed that the application of anti-NGF reduced the contractile responses of the rat isolated ileum apparently by decreasing the calcium influx from the extracellular medium.
Endothelin-1 (ET-1) and Nerve Growth Factor (NGF) are proteins, released from cancer-ridden tissues, which cause spontaneous pain and hypersensitivity to noxious stimuli. Here we examined the electrophysiological and behavioral effects of these two agents for evidence of their interactions. Individual small-medium cultured DRG sensory neurons responded to both ET-1 (50 nM, n=6) and NGF (100 ng/ml, n=4), with increased numbers of action potentials and decreased slow K+ currents; pre-exposure to ET-1 potentiated NGF´s actions, but not vice versa. Behaviorally, single intraplantar (i.pl.) injection of low doses of ET-1 (20 pmol) or NGF (100 ng), did not increase hindpaw tactile or thermal sensitivity, but their simultaneous injections sensitized the paw to both modalities. Daily i.pl. injections of low ET-1 doses in male rats caused tactile sensitization after 21 days, and enabled further tactile and thermal sensitization from low dose NGF, in ipsilateral and contralateral hindpaws. Single injections of 100 ng NGF, without changing the paw’s tactile sensitivity by itself, acutely sensitized the ipsilateral paw to subsequent injections of low ET-1. The sensitization from repeated low ET-1 dosing and the cross-sensitization between NGF and ET-1 were both significantly greater in female than in male rats. These findings reveal a synergistic interaction between cutaneously administered low doses of NGF and ET-1, which could contribute to cancer-related pain., A. Khodorova, Y. Zhang, G. Nicol, G. Strichartz., and Seznam literatury