Department of Urology, Loyola University Health System, Maywood, IL, USA.
Neuroscience. 2011 Jun 2;183:230-7. doi: 10.1016/j.neuroscience.2011.03.035. Epub 2011 Mar 30.
Visceral sensory afferents during disease or following injury often produce vague, diffuse body sensations, and pain referred to somatic targets. Alternatively, injury due to trauma or disease of somatic nerve targets can also lead to referred pain in visceral targets via a somatovisceral reflex. Both phenomenons are thought to be due to convergence of visceral and somatic afferents within the spinal cord. To investigate a potential peripheral influence for referred pain in visceral targets following somatic nerve injury, we examined whether a sciatic nerve injury known to produce hindpaw tactile hyperalgesia alters the frequency of micturition and the sensitivity of bladder-associated sensory neurons to pro-nociceptive chemokines. Adult female Sprague-Dawley rats received injections of cholera toxin B subunit conjugated to 555 into urinary bladder wall to retrogradely label visceral primary afferent neurons. After 7 days, the right sciatic nerve of these animals was subjected to a lysophosphatidylcholine (LPC)-induced focal demyelination injury. Pre- and post-injury tactile sensitivity in the hind paw and micturition frequency were assayed. Animals were allowed to survive for 14-28 days. Lumbosacral and lumbar dorsal root ganglia (DRG) ipsilateral to the nerve injury were acutely dissociated from sham and nerve injured animals. Bladder wall-associated sensory neurons identified via the retrograde marker were assayed for fluxes in intracellular calcium following administration of pro-nociceptive chemokines. The assayed chemokines included monocyte chemoattractant protein-1 (MCP1/CCL2) and stromal cell derived factor-1 alpha (SDF1/CXCL12). LPC nerve injured animals exhibited tactile hyperalgesia and increased micturition frequency for at least 28 days. Focal demyelination of the sciatic nerve also increased the number of injured L₄L₅ and non-injured L₆-S₂ bladder-associated sensory neurons that responded to MCP1 and SDF1 when compared with sensory neurons derived from uninjured naïve and sham-injured control animals. Taken together, these data suggest that some visceral hypersensitivity states may have a somatic origin. More importantly, nociceptive somatovisceral sensation may be mediated by upregulation of chemokine signaling in visceral sensory neurons.
内脏感觉传入在疾病或损伤后常产生模糊、弥散的全身感觉，并向躯体靶位放射痛。或者，躯体神经靶位的创伤或疾病引起的损伤也可以通过躯体-内脏反射导致内脏靶位的牵涉痛。这两种现象都被认为是由于内脏和躯体传入在脊髓内的会聚。为了研究躯体神经损伤后内脏靶位牵涉痛的潜在外周影响，我们研究了已知会产生后爪触觉过敏的坐骨神经损伤是否会改变排尿频率和膀胱相关感觉神经元对促伤害性趋化因子的敏感性。成年雌性 Sprague-Dawley 大鼠接受霍乱毒素 B 亚单位（CTB）注入膀胱壁以逆行标记内脏初级传入神经元。7 天后，这些动物的右侧坐骨神经受到溶血磷脂酰胆碱（LPC）诱导的局灶性脱髓鞘损伤。在损伤前和损伤后测定后爪的触觉敏感性和排尿频率。动物存活 14-28 天。对来自假手术和神经损伤动物的同侧腰骶和腰背部脊神经节（DRG）进行急性分离。通过逆行标记物鉴定的膀胱壁相关感觉神经元在给予促伤害性趋化因子后，测定细胞内钙流。所测定的趋化因子包括单核细胞趋化蛋白-1（MCP1/CCL2）和基质细胞衍生因子-1 ɑ（SDF1/CXCL12）。LPC 神经损伤动物表现出触觉过敏和至少 28 天的排尿频率增加。与来自未损伤的天真和假手术对照动物的感觉神经元相比，坐骨神经的局灶性脱髓鞘也增加了对 MCP1 和 SDF1 有反应的 L₄L₅ 和非损伤的 L₆-S₂ 膀胱相关感觉神经元的数量。总之，这些数据表明，一些内脏敏感性状态可能有躯体起源。更重要的是，伤害性躯体-内脏感觉可能是通过内脏感觉神经元中趋化因子信号的上调来介导的。
