Pain Signaling and Plasticity Laboratory, Department of Anesthesiology and Neurobiology, Duke University Medical Center, 595 LaSalle Street, GSRB-I, Room 1027A, DUMC 3094, Durham, NC, 27710, USA,
Pflugers Arch. 2013 Dec;465(12):1671-85. doi: 10.1007/s00424-013-1284-2. Epub 2013 May 1.
Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli. Itch-mediating primary sensory neurons are equipped with distinct receptors and ion channels for itch transduction, including Mas-related G protein-coupled receptors (Mrgprs), protease-activated receptors, histamine receptors, bile acid receptor, toll-like receptors, and transient receptor potential subfamily V1/A1 (TRPV1/A1). Recent progress has indicated the existence of an itch-specific neuronal circuitry. The MrgprA3-expressing primary sensory neurons exclusively innervate the epidermis of skin, and their central axons connect with gastrin-releasing peptide receptor (GRPR)-expressing neurons in the superficial spinal cord. Notably, ablation of MrgprA3-expressing primary sensory neurons or GRPR-expressing spinal cord neurons results in selective reduction in itch but not pain. Chronic itch results from dysfunction of the immune and nervous system and can manifest as neural plasticity despite the fact that chronic itch is often treated by dermatologists. While differences between acute pain and acute itch are striking, chronic itch and chronic pain share many similar mechanisms, including peripheral sensitization (increased responses of primary sensory neurons to itch and pain mediators), central sensitization (hyperactivity of spinal projection neurons and excitatory interneurons), loss of inhibitory control in the spinal cord, and neuro-immune and neuro-glial interactions. Notably, painful stimuli can elicit itch in some chronic conditions (e.g., atopic dermatitis), and some drugs for treating chronic pain are also effective in chronic itch. Thus, itch and pain have more similarities in pathological and chronic conditions.
瘙痒和疼痛密切相关但又不同。它们共享大量重叠的介质和受体，并且瘙痒反应神经元也对疼痛刺激敏感。介导瘙痒的初级感觉神经元配备了用于瘙痒转导的独特受体和离子通道，包括 Mas 相关 G 蛋白偶联受体（Mrgprs）、蛋白酶激活受体、组胺受体、胆汁酸受体、 Toll 样受体和瞬时受体电位亚家族 V1/A1（TRPV1/A1）。最近的进展表明存在一种特定于瘙痒的神经元回路。表达 MrgprA3 的初级感觉神经元专门支配皮肤的表皮，其中枢轴突与脊髓浅层中表达胃泌素释放肽受体（GRPR）的神经元相连。值得注意的是，MrgprA3 表达的初级感觉神经元或 GRPR 表达的脊髓神经元的消融导致瘙痒选择性减少而疼痛不减。慢性瘙痒是由于免疫系统和神经系统功能障碍引起的，尽管慢性瘙痒通常由皮肤科医生治疗，但它可以表现为神经可塑性。虽然急性疼痛和急性瘙痒之间存在显著差异，但慢性瘙痒和慢性疼痛具有许多相似的机制，包括外周敏化（初级感觉神经元对瘙痒和疼痛介质的反应增加）、中枢敏化（脊髓投射神经元和兴奋性中间神经元的过度活跃）、脊髓抑制性控制丧失，以及神经免疫和神经胶质相互作用。值得注意的是，在某些慢性疾病（例如特应性皮炎）中，疼痛刺激可引起瘙痒，一些用于治疗慢性疼痛的药物对慢性瘙痒也有效。因此，在病理和慢性条件下，瘙痒和疼痛具有更多的相似性。
