McGill University, Anesthesia Research Unit, Faculty of Medicine, Faculty of Dentistry and Alan Edwards Center for Research on Pain, Montréal, Québec, Canada.
Mol Pain. 2011 May 9;7:31. doi: 10.1186/1744-8069-7-31.
Systemic administration of cannabinoid agonists is known to reduce pain induced by bladder inflammation and to modulate cystometric parameters in vivo. We have previously reported that intravesical administration of a cannabinoid agonist reduces the electrical activity of bladder afferents under normal conditions. However, the effects of local activation of bladder cannabinoid receptors on afferent activity during inflammation are unknown. This study was aimed to assess the effects of intravesical administration of a cannabinoid agonist on the discharges of afferent fibers in inflamed bladders ex vivo. We also characterized the expression of CB1 receptors in the bladder and their localization and co-expression with TRPV1, a marker of nociceptive afferents.
Compared to untreated animals, afferent fiber activity in inflamed bladders was increased for intravesical pressures between 10 and 40 mmHg. Local treatment with a non selective cannabinoid agonist (AZ12646915) significantly reduced the afferent activity at intravesical pressures above 20 mmHg. This effect was blocked by AM251 but not by AM630 (selective for CB1 and CB2 respectively). Finally, CB1 was co-expressed with TRPV1 in control and inflamed bladders.
These results demonstrate that sensitization of bladder afferents induced by inflammation is partly suppressed by intravesical activation of cannabinoid receptors, an effect that appears to be mediated by CB1 receptors. Also, TRPV1 positive fibers were found to co-express CB1, supporting the hypothesis of a direct action of the cannabinoid agonist on nociceptive afferents. Taken together, these results indicate a peripheral modulation by the cannabinoid system of bladder hypersensitivity during inflammation.
全身给予大麻素激动剂已知可减轻膀胱炎症引起的疼痛，并在体内调节膀胱测压参数。我们之前曾报道过，膀胱内给予大麻素激动剂可降低正常情况下膀胱传入纤维的电活动。然而，局部激活膀胱大麻素受体对炎症期间传入活动的影响尚不清楚。本研究旨在评估膀胱内给予大麻素激动剂对炎症性膀胱传入纤维放电的影响。我们还描述了 CB1 受体在膀胱中的表达及其定位，并与 TRPV1（痛觉传入纤维的标志物）共表达。
与未处理的动物相比，在膀胱内压力为 10-40mmHg 时，传入纤维活动在炎症性膀胱中增加。局部给予非选择性大麻素激动剂（AZ12646915）可显著降低膀胱内压力高于 20mmHg 时的传入纤维活动。这种作用被 AM251 阻断，但被 AM630（分别对 CB1 和 CB2 具有选择性）阻断。最后，CB1 在对照和炎症性膀胱中与 TRPV1 共表达。
这些结果表明，炎症引起的膀胱传入纤维敏化部分被膀胱内大麻素受体的激活所抑制，这种作用似乎是由 CB1 受体介导的。此外，还发现 TRPV1 阳性纤维共表达 CB1，支持大麻素激动剂对伤害性传入纤维的直接作用假说。总之，这些结果表明，大麻素系统在炎症期间对膀胱过敏具有外周调节作用。
