Wang Zun-Yi, Wang Peiqing, Bjorling Dale E
Departments of Surgical Sciences, University of Wisconsin, Madison, WI, USA.
Departments of Surgical Sciences, University of Wisconsin, Madison, WI, USA.
Neurosci Lett. 2015 Mar 4;589:19-24. doi: 10.1016/j.neulet.2015.01.009. Epub 2015 Jan 6.
Nerve growth factor (NGF) is an important mediator of inflammatory pain, in part by sensitizing afferent nerve fibers, and expression of NGF is increased during bladder inflammation. We investigated whether intravesical instillation of the selective cannabinoid receptor 1 (CB1) agonist arachidonyl-2'-chloroethylamide (ACEA) affects NGF-induced increased bladder activity in female C57BL/6J wild-type (WT) mice. We also examined the effects of intravesical NGF in female fatty acid amide hydrolase knock-out (FAAH KO) mice. We found that CB1 and tyrosine kinase A (trkA, the high-affinity NGF receptor) were present in L6 dorsal root ganglion (DRG) afferent neurons and in bladders of both genotypes. Intravesical NGF increased bladder activity that was inhibited by intravesical ACEA in WT mice. The inhibitory effects of ACEA were reversed by the selective CB1 antagonist AM 251. Intravesical NGF failed to affect bladder activity in FAAH KO mice, and treatment with AM251, restored the stimulatory effects of NGF on the bladder in FAAH KO mice. These results indicate that activation of CB1 inhibits increased bladder activity induced by NGF.
神经生长因子（NGF）是炎性疼痛的重要介质，部分原因是它能使传入神经纤维敏感化，并且在膀胱炎症期间NGF的表达会增加。我们研究了膀胱内灌注选择性大麻素受体1（CB1）激动剂花生四烯酰-2'-氯乙酰胺（ACEA）是否会影响雌性C57BL/6J野生型（WT）小鼠中NGF诱导的膀胱活动增加。我们还研究了膀胱内注射NGF对雌性脂肪酸酰胺水解酶基因敲除（FAAH KO）小鼠的影响。我们发现CB1和酪氨酸激酶A（trkA，高亲和力NGF受体）存在于两种基因型小鼠的L6背根神经节（DRG）传入神经元和膀胱中。膀胱内注射NGF会增加WT小鼠的膀胱活动，而膀胱内注射ACEA可抑制这种活动。选择性CB1拮抗剂AM 251可逆转ACEA的抑制作用。膀胱内注射NGF对FAAH KO小鼠的膀胱活动没有影响，而用AM251治疗可恢复NGF对FAAH KO小鼠膀胱的刺激作用。这些结果表明，CB1的激活可抑制NGF诱导的膀胱活动增加。
