Divergent functions of the left and right central amygdala in visceral nociception.
Divergent functions of the left and right central amygdala in visceral nociception.
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DOI：
10.1097/j.pain.0000000000000830
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发表时间：
2017-04
期刊：
影响因子：
7.4
通讯作者：
Kolber BJ
中科院分区：
文献类型：
--
作者：
Sadler KE;McQuaid NA;Cox AC;Behun MN;Trouten AM;Kolber BJ
左右中央杏仁核（CeA）是参与躯体和内脏疼痛加工的边缘区域。这两个核不对称地参与躯体疼痛调节；身体两侧的疼痛样反应优先由右侧CeA驱动，并且以互惠的方式，身体两侧的伤害性躯体刺激主要改变右侧CeA的分子和生理活动。然而，这种侧化是否也存在于内脏疼痛加工中，以及左侧CeA在调节伤害性信息方面的功能尚不清楚。利用膀胱膨胀（UBD）和兴奋性光遗传学技术，在小鼠中证实了右侧CeA的前感觉功能。通道视紫红质-2介导的右侧CeA的激活增加了内脏运动反应（VMRs），而左侧CeA的激活没有影响。同样，在右侧CeA单侧输注垂体腺苷酸环化酶激活多肽后，ubd诱发的VMRs增加。为了确定内源性左CeA参与膀胱疼痛调节，在有害UBD期间，该区域被光遗传学沉默。Halorhodopsin （NpHR）介导的左侧CeA抑制增加了vmr，表明该区域具有持续的抗感觉功能。最后，在腹部机械感觉测试中评估左、右CeA的发散功能。在幼年动物中，通道视紫红质-2介导的右侧CeA的激活诱导了机械异常性疼痛，而在环磷酰胺诱导的膀胱致敏后，左侧CeA的激活逆转了参考膀胱疼痛样行为。总的来说，这些数据为在没有周围解剖不对称的情况下功能性脑侧化提供了证据。
The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.
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