2024年12月3日 (二) 15:39的版本

本页英文内容取自：经典教材医学生理学（第三版） (Medical Physiology, 3rd Edtion, Walter F Boron, published in 2016)

中文内容由 BH1RBH (Jack Tan) 粗糙翻译

蓝色 【注】 后内容为 BH1RBH (Jack Tan) 所加之注释

躯体感觉受体、本体感觉和疼痛

Somatic Sensory Receptors, Proprioception, and Pain

1 概述

Somatic sensation is the most widespread and diverse of the body’s sensory systems (soma means “body” in Greek). Its receptors are distributed throughout the body instead of being condensed into small and specialized sensory surfaces, as most other sensory systems are arranged. Somatosensory receptors cover the skin, subcutaneous tissue, skeletal muscles, bones and joints, major internal organs, epithelia, and cardiovascular system. These receptors also vary widely in their specificity. The body has mechanoreceptors to transduce pressure, stretch, vibration, and tissue damage; thermoreceptors to gauge temperature; and chemoreceptors to sense a variety of substances. Somatic sensation (or somesthesia) is usually considered to be a combination of at least four sensory modalities: the senses of touch, temperature, body position (proprioception), and pain (nociception).

躯体感觉是身体最广泛和最多样化的感觉系统（soma 在希腊语中意为“身体”）。它的受体分布在整个身体，而不是像大多数其他感觉系统那样浓缩成小而特殊的感觉表面。体感受体覆盖皮肤、皮下组织、骨骼肌、骨骼和关节、主要内脏器官、上皮细胞和心血管系统。这些受体的特异性也差异很大。身体有机械感受器来传导压力、拉伸、振动和组织损伤;温度感受器用于测量温度;和化学感受器来感知各种物质。躯体感觉（或感觉）通常被认为是至少四种感觉模式的组合：触觉、温度、身体位置（本体感觉）和疼痛（伤害感受）。

2 皮肤中的各种感觉末梢传导机械、热和化学刺激

A variety of sensory endings in the skin transduce mechanical, thermal, and chemical stimuli

To meet a wide array of sensory demands, many kinds of specialized receptors are required. Somatic sensory receptors range from simple bare nerve endings to complex combinations of nerve, muscle, connective tissue, and supporting cells. As we have seen, the other major sensory systems have only one type of sensory receptor or a set of very similar subtypes.

为了满足广泛的感觉需求，需要多种专门的受体。躯体感觉受体的范围从简单的裸露神经末梢到神经、肌肉、结缔组织和支持细胞的复杂组合。正如我们所看到的，其他主要的感觉系统只有一种类型的感觉受体或一组非常相似的亚型。

Mechanoreceptors, which are sensitive to physical distortion such as bending or stretching, account for many of the somatic sensory receptors. They exist throughout our bodies and monitor the following: physical contact with the skin, blood pressure in the heart and vessels, stretching of the gut and bladder, and pressure on the teeth. The transduction site of these mechanoreceptors is one or more unmyelinated axon branches. Our progress in understanding the molecular nature of mechanosensory transduction has been relatively slow. Similar to the transduction process in hair cells, that in cutaneous mechanoreceptive nerve endings probably involves the gating of ion channels. Some of these channels belong to the TRP superfamily (see Table 6-2, family No. 5).

机械感受器对弯曲或拉伸等物理变形敏感，占躯体感觉受体的许多。它们存在于我们的身体中，监测以下内容：与皮肤的物理接触、心脏和血管中的血压、肠道和膀胱的伸展以及牙齿的压力。这些机械感受器的转导位点是一个或多个无髓轴突分支。我们在理解机械感应转导的分子性质方面的进展相对较慢。与毛细胞中的转导过程类似，皮肤机械感受神经末梢的转导过程可能涉及离子通道的门控。其中一些通道属于 TRP 超家族（参见表 6-2，家族 5）。

Thermoreceptors respond best to changes in temperature, whereas chemoreceptors are sensitive to various kinds of chemical alterations. In the next three sections, we discuss mechanoreceptors, thermoreceptors, and chemoreceptors that are located in the skin.

温度感受器对温度变化反应最好，而化学感受器对各种化学变化敏感。在接下来的三节中，我们将讨论位于皮肤中的机械感受器、热感受器和化学感受器。

3 皮肤中的机械感受器对特定刺激（如振动和稳定压力）敏感

Mechanoreceptors in the skin provide sensitivity to specific stimuli such as vibration and steady pressure

Skin protects us from our environment by preventing evaporation of body fluids, invasion by microbes, abrasion, and damage from sunlight. However, skin also provides our most direct contact with the world. The two major types of mammalian skin are hairy and glabrous. Glabrous skin (or hairless skin) is found on the palms of our hands and fingertips and on the soles of our feet and pads of our toes (Fig. 15-26A).

皮肤通过防止体液蒸发、微生物入侵、擦伤和阳光损伤来保护我们免受环境的影响。然而，皮肤也提供了我们与世界最直接的接触。哺乳动物皮肤的两种主要类型是毛状和无毛。无毛皮肤（或无毛皮肤）存在于我们的手掌和指尖以及脚底和脚趾垫上（图 15-26A）。

Hairy skin makes up most of the rest and differs widely in its hairiness. Both types of skin have an outer layer, the epidermis, and an inner layer, the dermis, and sensory receptors innervate both. The receptors in the skin are sensitive to many types of stimuli and respond when the skin is vibrated, pressed, pricked, or stroked, or when its hairs are bent or pulled. These are quite different kinds of mechanical energy, yet we can feel them all and easily tell them apart. Skin also has exquisite sensitivity; for example, we can reliably feel a dot only 0.006 mm high and 0.04 mm across when it is stroked across a fingertip. The standard Braille dot is 167 times higher!

毛茸茸的皮肤占其余的大部分，毛茸茸的程度差异很大。两种类型的皮肤都有外层（表皮）和内层（真皮），感觉受体支配两者。皮肤中的受体对多种类型的刺激很敏感，当皮肤受到振动、按压、刺痛或抚摸，或者皮肤毛发弯曲或拉扯时，它们会做出反应。这些是完全不同的机械能，但我们可以感觉到它们并很容易区分它们。皮肤也有精致的敏感;例如，当用指尖抚摸一个只有 0.006 毫米高和 0.04 毫米宽的点时，我们可以可靠地感觉到它。标准的盲文圆点高出 167 倍！

The sensory endings in the skin take many shapes, and most of them are named after the 19th-century European histologists who observed them and made them popular. The largest and best-studied mechanoreceptor is Pacini’s corpuscle, which is up to 2 mm long and almost 1 mm in diameter (see Fig. 15-26B). Pacini’s corpuscle is located in the subcutaneous tissue of both glabrous and hairy skin. It has an ovoid capsule with 20 to 70 onion-like, concentric layers of connective tissue and a nerve terminal in the middle. The capsule is responsible for the rapidly adapting response of the Pacini’s corpuscle. When the capsule is compressed, energy is transferred to the nerve terminal, its membrane is deformed, and mechanosensitive channels open. Current flowing through the channels generates a depolarizing receptor potential that, if large enough, causes the axon to fire an action potential (see Fig. 15-26B, left panel). However, the capsule layers are slick, with viscous fluid between them. If the stimulus pressure is maintained, the layers slip past one another and transfer the stimulus energy away so that the underlying axon terminal is no longer deformed and the receptor potential dissipates (see Fig. 15-26B, right panel). When pressure is released, the events reverse themselves and the terminal is depolarized again. In this way, the non-neural covering of Pacini’s corpuscle specializes the corpuscle for sensing of vibrations and makes it almost unresponsive to steady pressure. Pacini’s corpuscle is most sensitive to vibrations of 200 to 300 Hz, and its threshold increases dramatically below 50 Hz and above ~500 Hz. The sensation evoked by stimulation of Pacini’s corpuscle is a poorly localized humming feeling.

皮肤的感觉末梢有多种形状，其中大多数以 19 世纪的欧洲组织学家命名，他们观察了它们并使它们流行起来。最大和研究最深入的机械感受器是帕西尼小体 (Pacini’s corpuscle)，它长达 2 毫米，直径近 1 毫米（见图 15-26B）。帕西尼小体位于无毛和多毛皮肤的皮下组织中。它有一个卵形胶囊，有 20 到 70 个洋葱状的同心结缔组织和中间的神经末梢。该囊负责帕西尼小体的快速适应反应。当胶囊被压缩时，能量被转移到神经末梢，它的膜变形，机械敏感通道打开。流经通道的电流产生去极化受体电位，如果足够大，会导致轴突触发动作电位（参见图 15-26B，左图）。然而，胶囊层很光滑，它们之间有粘性液体。如果刺激压力保持不变，各层会相互滑过并将刺激能量转移出去，这样下面的轴突末端不再变形，受体电位消散（见图 15-26B，右图）。当压力释放时，事件会自行反转，末端再次去极化。通过这种方式，帕西尼小体的非神经覆盖物使小体专门用于感知振动，使其对稳定的压力几乎没有反应。帕西尼小体对 200 到 300 Hz 的振动最敏感，其阈值在低于 50 Hz 和高于 ~500 Hz 时急剧增加。刺激 Pacini 小体所引起的感觉是一种定位不佳的嗡嗡声。

Werner Loewenstein and colleagues in the 1960s showed the importance of the Pacini corpuscle’s capsule to its frequency sensitivity. With fine microdissection, they were able to strip away the capsule from single corpuscles. They found that the resultant naked nerve terminal is much less sensitive to vibrating stimuli and much more sensitive to steady pressure. Clearly, the capsule modifies the sensitivity of the bare mechanoreceptive axon. The encapsulated Pacini corpuscle is an example of a rapidly adapting sensor, whereas the decapsulated nerve ending behaves like a slowly adapting sensor.

Werner Loewenstein 及其同事在 1960 年代证明了帕西尼小球胶囊对其频率灵敏度的重要性。通过精细的显微解剖，他们能够从单个小球上剥离胶囊。他们发现，由此产生的裸露神经末梢对振动刺激的敏感度要低得多，而对稳定的压力要敏感得多。显然，该胶囊改变了裸露机械感受轴突的敏感性。封装的帕西尼小体是快速适应传感器的一个例子，而解封的神经末梢的行为类似于缓慢适应的传感器。

Several other types of encapsulated mechanoreceptors are located in the dermis, but none has been studied as well as Pacini’s corpuscle. Meissner’s corpuscles (see Fig. 15-26A) are located in the ridges of glabrous skin and are about one tenth the size of Pacini’s corpuscles. They are rapidly adapting, although less so than Pacini’s corpuscles. Ruffini’s corpuscles resemble diminutive Pacini’s corpuscles and, like Pacini’s corpuscles, occur in the subcutaneous tissue of both hairy and glabrous skin. Their preferred stimuli might be called “fluttering” vibrations. As relatively slowly adapting receptors, they respond best to low frequencies. Merkel’s disks are also slowly adapting receptors made from a flattened, non-neural epithelial cell that synapses on a nerve terminal. They lie at the border of the dermis and epidermis of glabrous skin. It is not clear whether it is the nerve terminal or epithelial cell that is mechanosensitive. The nerve terminals of Krause’s end bulbs appear knotted. They innervate the border areas of dry skin and mucous membranes (e.g., around the lips and external genitalia) and are probably rapidly adapting mechanoreceptors.

其他几种类型的包膜机械感受器位于真皮中，但没有一种像帕西尼小体那样被研究过。迈斯纳小体 (Meissner’s corpuscles)（见图 15-26A）位于无毛皮肤的脊上，大约是帕西尼小球的十分之一大小。它们正在迅速适应，尽管不如帕西尼小体适应。鲁菲尼小体 (Ruffini’s corpuscles)类似于小的帕西尼小体，并且与帕西尼小体一样，出现在多毛和无毛皮肤的皮下组织中。他们喜欢的刺激可能被称为“颤动”振动。作为适应相对较慢的受体，它们对低频的反应最好。默克尔椎间盘也在缓慢适应由扁平的非神经上皮细胞制成的受体，该细胞在神经末梢上形成突触。它们位于无毛皮肤的真皮和表皮的边界。目前尚不清楚是神经末梢还是上皮细胞对机械敏感。Krause 末端球的神经末梢似乎打结了。它们支配干燥皮肤和粘膜的边界区域（例如，嘴唇和外生殖器周围），并且可能是快速适应的机械感受器。

The receptive fields of different types of skin receptors vary greatly in size. Pacini’s corpuscles have extremely broad receptive fields (Fig. 15-27A), whereas those of Meissner’s corpuscles (see Fig. 15-27B) and Merkel’s disks are very small. The last two seem to be responsible for the ability of the fingertips to make very fine tactile discriminations. Small receptive fields are an important factor in achieving high spatial resolution. Resolution varies widely, a fact easily demonstrated by measuring the skin’s two-point discrimination. Bend a paper clip into a U shape. Vary the distance between the tips and test how easily you can distinguish the touch of one tip versus two on your palm, your fingertips, your lips, your back, and your foot. To avoid bias, a colleague—rather than you—should apply the stimulus. Compare the results with standardized data (see Fig. 15-27C).

不同类型皮肤受体的感受野大小差异很大。帕西尼小球具有极宽的感受野（图 15-27A），而迈斯纳小球（见图 15-27B）和默克尔小球的感受野非常小。后两个似乎是指尖进行非常精细的触觉辨别能力的原因。小感受野是实现高空间分辨率的重要因素。分辨率差异很大，通过测量皮肤的两点区分力很容易证明这一事实。将回形针弯曲成 U 形。改变尖端之间的距离，并测试区分一个尖端和两个尖端在手掌、指尖、嘴唇、背部和脚上的触摸的难易程度。为避免偏见，应该由同事（而不是您）来实施刺激。将结果与标准化数据进行比较（参见图 15-27C）。

The identities of somatosensory transduction molecules remain elusive. A variety of TRP channel subtypes transduce mechanical stimuli in invertebrate species (e.g., Drosophila, Caenorhabditis elegans). In mammals, rapidly adapting ion channels are associated with receptors for light touch, and several of the TRPC channels appear to be involved in sensitivity to light touch in mice. A non-TRP protein named Piezo2 is associated with rapidly adapting mechanosensory currents in mouse sensory neurons, and knocking down the expression of Piezo2 expression causes deficits in touch. Other mechanosensory channels are expressed in some sensory neurons, including TRPA1 and TRPV4, two-pore potassium channels (KCNKs), and degenerin/epithelial sodium channels (especially ASIC1 to ASIC3 and their accessory proteins), but their roles in mammalian mechanosensation are still controversial.

体感转导分子的身份仍然难以捉摸。多种 TRP 通道亚型转导无脊椎动物物种（例如，果蝇、秀丽隐杆线虫）的机械刺激。在哺乳动物中，快速适应的离子通道与轻触受体有关，并且几个 TRPC 通道似乎与小鼠对轻触的敏感性有关。一种名为 Piezo2 的非 TRP 蛋白与小鼠感觉神经元中快速适应的机械感应电流有关，敲低 Piezo2 表达会导致触觉缺陷。其他机械感觉通道在一些感觉神经元中表达，包括 TRPA1 和 TRPV4、双孔钾通道 （KCNK） 和简并蛋白/上皮钠通道（尤其是 ASIC1 至 ASIC3 及其辅助蛋白），但它们在哺乳动物机械感觉中的作用仍然存在争议。

One reason it is difficult to identify mechanosensory channels is that they often need to be associated with other cellular components in order to be sensitive to mechanical stimuli. The mechanisms by which mechanical force is transferred from cells and their membranes to mechanosensitive channels are unclear. Ion channels may be physically coupled to either extracellular structures (e.g., collagen fibers) or cytoskeletal components (e.g., actin, microtubules) that transfer energy from deformation of the cell to the gating mechanism of the channel. Mechanically gated ion channels of sensory neurons, including those requiring Piezo2, depend on the actin cytoskeleton. Some channels may be sensitive to stress, sheer, or curvature of the lipid bilayer itself and require no other types of anchoring proteins. Other channels may respond to mechanically triggered second messengers such as DAG (acting directly on the channel) or IP3 (acting indirectly via an IP3 receptor).

难以识别机械感觉通道的一个原因是，它们通常需要与其他细胞成分相关联，以便对机械刺激敏感。机械力从细胞及其膜传递到机械敏感通道的机制尚不清楚。离子通道可以物理偶联到细胞外结构（例如胶原纤维）或细胞骨架成分（例如肌动蛋白、微管），这些细胞将能量从细胞变形传递到通道的门控机制。感觉神经元的机械门控离子通道，包括需要 Piezo2 的神经元，取决于肌动蛋白细胞骨架。一些通道可能对脂质双层本身的应力、剪切或弯曲敏感，不需要其他类型的锚定蛋白。其他通道可能会响应机械触发的第二信使，例如 DAG（直接作用于通道）或 IP3（通过 IP3 受体间接作用）。

Two things determine the sensitivity of spatial discrimination in an area of skin. The first is the size of the receptors’ receptive fields—if they are small, the two tips of your paper clip are more likely to stimulate different sets of receptors. The second parameter that determines spatial discrimination is the density of the receptors in the skin. Indeed, two-point discrimination of the fingertips is better than that of the palm, even though their receptive fields are the same size. The key to finer discrimination in the fingertips is their higher density of receptors. Crowding more receptors into each square millimeter of fingertip has a second advantage: because the CNS receives more information per stimulus, it has a better chance of detecting very small stimuli.

有两件事决定了皮肤区域空间辨别的敏感度。首先是受体感受野的大小——如果它们很小，你的回形针的两个尖端更有可能刺激不同的受体组。决定空间辨别力的第二个参数是皮肤中受体的密度。事实上，指尖的两点辨别能力比手掌的两点辨别能力要好，即使它们的感受野大小相同。指尖更精细辨别的关键是它们更高密度的受体。将更多的受体塞进每平方毫米的指尖还有第二个好处：因为 CNS 每次刺激接收到更多信息，所以它有更好的机会检测到非常小的刺激。

Although we rarely think about it, hair is a sensitive part of our somatic sensory system. For some animals, hairs are a major sensory system. Rodents whisk long facial vibrissae (hairs) and feel the texture, distance, and shape of their local environment. Hairs grow from follicles embedded in the skin, and each follicle is richly innervated by free mechanoreceptive nerve endings that either wrap around it or run parallel to it. Bending of the hair causes deformation of the follicle and surrounding tissue, which stretches, bends, or flattens the nerve endings and increases or decreases their firing frequency. Various mechanoreceptors innervate hair follicles, and they may be either slowly or rapidly adapting.

虽然我们很少考虑它，但头发是我们躯体感觉系统的敏感部分。对于一些动物来说，毛发是一个主要的感觉系统。啮齿动物拂动长长的面部触须（毛发），感受当地环境的质地、距离和形状。毛发从嵌入皮肤的毛囊中长出，每个毛囊都由游离的机械感受神经末梢丰富地支配，这些神经末梢要么包裹着它，要么与它平行。头发弯曲会导致毛囊和周围组织变形，从而拉伸、弯曲或压平神经末梢，并增加或减少其放电频率。各种机械感受器支配毛囊，它们可能缓慢或迅速地适应。

4 独立的温度感受器检测暖和冷

Separate thermoreceptors detect warmth and cold

Neurons are sensitive to changes in temperature, as are all of life’s chemical reactions. Neuronal temperature sensitivity has two consequences: first, neurons can measure temperature; but second, to work properly, most neural circuits need to be kept at a relatively stable temperature. Neurons of the mammalian CNS are especially vulnerable to temperature changes. Whereas skin tissue temperatures can range from 20°C to 40°C without harm or discomfort, brain temperature must be near 37°C to avoid serious dysfunction. The body has complex systems to control brain (i.e., body core) temperature tightly (see pp. 1198–1201). Even though all neurons are sensitive to temperature, not all neurons are thermoreceptors.

神经元对温度的变化很敏感，生命中的所有化学反应也是如此。神经元对温度的敏感有两个后果：首先，神经元可以测量温度;但其次，要正常工作，大多数神经回路需要保持在相对稳定的温度下。哺乳动物 CNS 的神经元特别容易受到温度变化的影响。虽然皮肤组织温度可以在 20°C 到 40°C 之间而不会造成伤害或不适，但大脑温度必须接近 37°C 以避免严重功能障碍。身体有复杂的系统来严格控制大脑（即身体核心）的温度（见第 1198-1201 页）。尽管所有神经元都对温度敏感，但并非所有神经元都是温度感受器。

Because of specific membrane mechanisms, some neurons are extremely sensitive to temperature and seem to be adapted to the job of sensing it. Although many temperature-sensitive neurons are present in the skin, they are also clustered in the hypothalamus and the spinal cord (see pp. 1198–1199). The hypothalamic temperature sensors, like their cutaneous counterparts, are important for regulation of the physiological responses that maintain stable body temperature.

由于特定的膜机制，一些神经元对温度极为敏感，并且似乎适应了感知温度的工作。尽管皮肤中存在许多对温度敏感的神经元，但它们也聚集在下丘脑和脊髓中（见第 1198-1199 页）。下丘脑温度传感器与它们的皮肤传感器一样，对于调节维持稳定体温的生理反应很重要。

Perceptions of temperature apparently reflect warmth and cold receptors located in the skin. Thermoreceptors, like mechanoreceptors, are not spread uniformly across the skin. When you map the skin’s sensitivity to temperature with a small cold or warm probe, you find spots ~1 mm across that are especially sensitive to either warmth or cold, but not to both. In addition, some areas of skin in between are relatively insensitive. The spatial dissociation of the hot and cold maps shows that they are separate submodalities, with separate receptors to encode each. Recordings from single sensory fibers have confirmed this conclusion. The responses of both warmth and cold thermoreceptors adapt during long stimuli, as many sensory receptors commonly do. Most cutaneous thermoreceptors are probably free nerve endings, without obvious specialization. Their axons are small, either unmyelinated C fibers or the smallest-diameter myelinated Aδ fibers (see Table 12-1).

对温度的感知显然反映了位于皮肤中的温暖和寒冷感受器。温度感受器与机械感受器一样，不会均匀分布在皮肤上。当您使用小型冷探头或暖探头绘制皮肤对温度的敏感性图时，您会发现 ~1 毫米宽的点对暖或冷特别敏感，但对两者都不敏感。此外，介于两者之间的某些皮肤区域相对不敏感。热图和冷图的空间解离表明它们是独立的子模态，每个子模态都有单独的受体来编码。来自单个感觉纤维的记录证实了这一结论。温暖和寒冷的热感受器的反应都会在长时间刺激期间进行调整，就像许多感觉感受器通常所做的那样。大多数皮肤热感受器可能是游离神经末梢，没有明显的特化。它们的轴突很小，要么是无髓 C 纤维，要么是最小直径的有髓 Aδ 纤维（见表 12-1）。

We can perceive changes in our average skin temperature of as little as 0.01°C. Within the skin are separate types of thermoreceptors that are sensitive to a range of relatively hot or cold temperatures. Figure 15-28A shows how the steady discharge rate of both types of receptors varies with temperature. Warmth receptors begin firing above ~30°C and increase their firing rate until 44°C to 46°C, beyond which the rate falls off steeply and a sensation of pain begins, presumably mediated by nociceptive endings (see the next section). Cold receptors have a much broader temperature response. They are relatively quiet at skin temperatures of ~40°C, but their steady discharge rate increases as the temperature falls to 24°C to 28°C. Further decreases in temperature cause the steady discharge rate of the cold receptors to decrease until the temperature falls to ~10°C. Below that temperature, firing ceases and cold becomes an effective local anesthetic.

我们可以感知到低至 0.01°C 的平均体表温度变化。 皮肤内有不同类型的热感受器，它们对一系列相对较热或较冷的温度敏感。图 15-28A 显示了两种受体的稳态放电率如何随温度变化。温暖感受器在 ~30°C 以上开始放电，并增加其放电速率，直到 44°C 至 46°C，超过此温度后，速率急剧下降并开始疼痛感，可能是由伤害性结束介导的（见下一节）。冷受体具有更广泛的温度响应。它们在 ~40°C 的皮肤温度下相对安静，但随着温度降至 24°C 至 28°C，其稳定的放电速率会增加。 温度进一步降低会导致冷接收器的稳定放电速率降低，直到温度降至 ~10°C。 低于该温度时，燃烧停止，寒冷成为一种有效的局部麻醉剂。

In addition to the tonic response just described (i.e., the steady discharge rate), cold receptors also have a phasic response that enables them to report changes in temperature. As shown in Figure 15-28B, when the temperature suddenly shifts from 20.5°C to 15.2°C (both points are to the left of the peak in Fig. 15-28A), the firing rate transiently increases (i.e., the phasic response). However, the new steady-state level is lower, as suggested by the left pair of points in Figure 15-28A. When the temperature suddenly shifts from 35°C to 31.5°C (both points are to the right of the peak in Fig. 15-28A), the firing rate transiently increases, and the new steady-state level is higher, as suggested by the right pair of points in Figure 15-28A.

除了刚才描述的强直反应（即稳定的放电率）外，冷受体还具有阶段性反应，使它们能够报告温度的变化。如图 15-28B 所示，当温度突然从 20.5°C 变为 15.2°C 时（两个点都在图 15-28A 中峰值的左侧），放电速率瞬时增加（即相位响应）。然而，新的稳态水平较低，如图 15-28A 中左边的一对点所示。当温度突然从 35°C 变为 31.5°C 时（图 15-28A 中两个点都在峰值的右侧），放电速率瞬时增加，新的稳态水平更高，如图 15-28A 中右边的一对点所示。

The transduction of relatively warm temperatures is carried out by several types of TRPV channels (specifically TRPV1 to TRPV4—see Table 6-2, family No. 5) expressed in thermoreceptors. TRPV1 is a vanilloid receptor—it is activated by the vanilloid class of compounds that includes capsaicin, the pungent ingredient that gives spicy foods their burning quality. Aptly enough, chili peppers taste “hot” because they activate some of the same ion channels that heat itself activates! TRPV1 and TRPV2 channels have painfully high temperature thresholds (~43°C and ~50°C, respectively) and thus help mediate the noxious aspects of thermoreception (see p. 387). Other TRPV channels (TRPV3 and TRPV4) are activated at more moderate temperatures and presumably provide our sensations of warmth. Yet another TRP channel, TRPM8, mediates sensations of moderate cold. TRPM8 channels begin to open at temperatures below ~27°C and are maximally activated at 8°C. In a remarkable analogy to the hot-sensitive TRPV1 channel (the capsaicin receptor), the cool-sensitive TRPM8 channel is a menthol receptor. Menthol evokes sensations of cold because it activates the same ion channel that is opened by cold temperatures.

相对较暖温度的转导由热感受器中表达的几种类型的 TRPV 通道（特别是 TRPV1 到 TRPV4 — 参见表 6-2，家族 5）进行。TRPV1 是一种香草素受体——它被香草素类化合物激活，其中包括辣椒素，辣椒素是一种刺激性成分，使辛辣食物具有燃烧感。恰如其分地，辣椒尝起来“辣”，因为它们激活了一些与加热本身相同的离子通道！TRPV1 和 TRPV2 通道具有非常高的温度阈值（分别为 ~43°C 和 ~50°C），因此有助于介导热接收的有害方面（参见第 387 页）。其他 TRPV 通道（TRPV3 和 TRPV4）在更温和的温度下被激活，并可能为我们提供温暖的感觉。另一个 TRP 通道 TRPM8 介导中度寒冷的感觉。TRPM8 通道在低于 ~27°C 的温度下开始打开，并在 8°C 时最大激活。 与热敏感的 TRPV1 通道（辣椒素受体）有一个显著的类比，冷敏感的 TRPM8 通道是一种薄荷醇受体。薄荷醇会引起寒冷的感觉，因为它会激活与低温相同的离子通道。

5 伤害感受器是传递痛苦刺激的特殊感觉末梢

Nociceptors are specialized sensory endings that transduce painful stimuli

Physical energy that is informative at low and moderate levels can be destructive at higher intensity. Sensations of pain motivate us to avoid such situations. Nociceptors are the receptors mediating acutely painful feelings to warn us that body tissue is being damaged or is at risk of being damaged (as the Latin roots imply: nocere [to hurt] + recipere [to receive]). The pain-sensing system is entirely separate from the other modalities we have discussed; it has its own peripheral receptors and a complex, dispersed, chemically unique set of central circuits. Nociceptors are free nerve endings, widely distributed throughout the body. They innervate the skin, bone, muscle, most internal organs, blood vessels, and heart. Ironically, nociceptors are generally absent from the brain substance itself, although they are in the meninges.

在低水平和中等水平下提供信息的物理能量在高强度下可能具有破坏性。痛苦的感觉促使我们避免这种情况。伤害感受器是介导剧烈痛苦情绪的受体，以警告我们身体组织正在受损或有受损的风险（正如拉丁词根所暗示的：nocere [伤害] + recipere [接收]）。疼痛感应系统与我们讨论过的其他模式完全分开;它有自己的外周受体和一组复杂、分散、化学独特的中央回路。伤害感受器是游离神经末梢，广泛分布于全身。它们支配皮肤、骨骼、肌肉、大多数内脏器官、血管和心脏。具有讽刺意味的是，尽管伤害感受器位于脑膜中，但大脑物质本身通常不存在。

Nociceptors vary in their selectivity. Mechanical nociceptors, some of which are quite selective, respond to strong pressure—in particular, pressure from sharp objects. A subset of nociceptors expresses Mas-related G protein– coupled receptor D (MrgprD); genetic ablation of just these neurons makes mice insensitive to noxious mechanical stimuli without affecting their responses to painful heat or cold. TRPA1 channels are involved in some forms of painrelated mechanosensation, and they may transduce stimuli that trigger pain originating from viscera such as the colon and bladder.

伤害感受器的选择性各不相同。机械伤害感受器，其中一些非常有选择性，对强大的压力做出反应——特别是来自尖锐物体的压力。伤害感受器的一个子集表达 Mas 相关 G 蛋白偶联受体 D (MrgprD)；仅这些神经元的基因消融使小鼠对有害的机械刺激不敏感，而不会影响它们对痛苦的热或冷的反应。TRPA1 通道参与某些形式的疼痛相关机械感觉，它们可能会转导触发源自内脏（如结肠和膀胱）的疼痛的刺激。

Thermal nociceptors signal either burning heat (above ~45°C, when tissues begin to be destroyed) or unhealthy cold; the heat-sensitive nociceptive neurons express the TRPV1 and TRPV2 channels, whereas the cold-sensitive nociceptors express TRPA1 and TRPM8 channels. A uniquely cold-resistant Na+ channel, Nav1.8, allows cold-sensitive nociceptors to continue firing action potentials even at temperatures low enough to silence other neurons.

热伤害感受器发出灼热（高于 ~45°C，当组织开始被破坏时）或不健康的寒冷的信号；热敏感伤害感受神经元表达 TRPV1 和 TRPV2 通道，而冷敏感伤害感受器表达 TRPA1 和 TRPM8 通道。独特的耐寒 Na + 通道 Nav1.8 允许对寒冷敏感的伤害感受器即使在足够低的温度下也能继续激发动作电位，使其他神经元保持沉默。

Chemical nociceptors, which are mechanically insensitive, respond to a variety of agents, including K+, extremes of pH, neuroactive substances such as histamine and bradykinin from the body itself, and various irritants from the environment. Some chemosensitive nociceptors may express TRP channels that respond to, among other things, plant-derived irritants such as capsaicin (TRPV1), menthol (TRPM8), and the pungent derivatives of mustard and garlic (TRPA1).

化学伤害感受器在机械上不敏感，对多种试剂有反应，包括 K+、极端 pH 值、来自人体本身的神经活性物质（如组胺和缓激肽）以及来自环境的各种刺激物。一些化疗敏感的伤害感受器可能表达 TRP 通道，这些通道对植物来源的刺激物有反应，例如辣椒素 （TRPV1）、薄荷醇 （TRPM8） 以及芥末和大蒜的刺激性衍生物 （TRPA1）。

Finally, polymodal nociceptors are single nerve endings that are sensitive to combinations of mechanical, thermal, and chemical stimuli. Nociceptive axons include both fast Aδ fibers and slow, unmyelinated C fibers. Aδ axons mediate sensations of sharp, intense pain; C fibers elicit more persistent feelings of dull, burning pain. The Na+ channel Nav1.7 has a particularly interesting relationship to pain. Patients with loss-of-function mutations of Nav1.7 are insensitive to noxious stimuli and experience repeated injuries because they lack protective reflexes. Several gain-of-function Nav1.7 mutations cause channel hyperexcitability and syndromes of intense chronic pain.

最后，多模式伤害感受器是对机械、热和化学刺激的组合敏感的单神经末梢。伤害性轴突包括快 Aδ 纤维和慢速无髓 C 纤维。Aδ 轴突介导剧烈疼痛的感觉；C 纤维会引起更持久的钝痛、灼痛感。Na+ 通道 Nav1.7 与疼痛的关系特别有趣。Nav1.7 功能丧失突变的患者对有害刺激不敏感，并且由于缺乏保护性反射而反复受伤。几种功能获得性 Nav1.7 突变导致通道过度兴奋和剧烈慢性疼痛综合征。

Sensations of pain can be modulated in a variety of ways. Skin, joints, or muscles that have been damaged or inflamed are unusually sensitive to further stimuli. This phenomenon is called hyperalgesia, and it can be manifested as a reduced threshold for pain, an increase in perceived intensity of painful stimuli, or spontaneous pain. Primary hyperalgesia occurs within the area of damaged tissue, but within ~20 minutes after an injury, tissues surrounding a damaged area may become supersensitive by a process called secondary hyperalgesia. Hyperalgesia seems to involve processes near peripheral receptors (Fig. 15-29) as well as mechanisms in the CNS.

疼痛的感觉可以通过多种方式进行调节。受损或发炎的皮肤、关节或肌肉对进一步的刺激异常敏感。这种现象称为痛觉过敏，它可以表现为疼痛阈值降低、感知到的疼痛刺激强度增加或自发性疼痛。原发性痛觉过敏发生在受损组织区域内，但在受伤后大约 20 分钟内，受损区域周围的组织可能会因称为继发性痛觉过敏的过程而变得超级敏感。痛觉过敏似乎涉及外周受体附近的过程 （图 15-29） 以及 CNS 中的机制。

Damaged skin releases a variety of chemical substances from its many cell types, blood cells, and nerve endings. These substances—sometimes called the inflammatory soup—include neurotransmitters (e.g., glutamate, serotonin, adenosine, ATP), peptides (e.g., substance P, bradykinin), various lipids (e.g., prostaglandins, endocannabinoids), proteases, neurotrophins, cytokines, and chemokines, K+, H+, and others; they trigger the set of local responses that we know as inflammation. As a result, blood vessels become more leaky and cause tissue swelling (or edema) and redness (see Box 20-1). Nearby mast cells release the chemical histamine, which directly excites nociceptors.

受损的皮肤会从其多种细胞类型、血细胞和神经末梢释放出各种化学物质。这些物质（有时称为炎症汤）包括神经递质（例如谷氨酸、血清素、腺苷、ATP）、肽（例如 P 物质、缓激肽）、各种脂质（例如前列腺素、内源性大麻素）、蛋白酶、神经营养因子 (NGF, Nerve Growth Factor)、细胞因子和趋化因子、K+、H+ 等；它们触发了我们称为炎症的一组局部反应。结果，血管变得更加渗漏，并导致组织肿胀（或水肿）和发红（见方框 20-1）。附近的肥大细胞释放化学组胺，直接激发伤害感受器。

By a mechanism called the axon reflex, action potentials can propagate along nociceptive axons from the site of an injury into side branches of the same axon that innervate neighboring regions of skin. The spreading axon branches of the nociceptors themselves may release substances that sensitize nociceptive terminals and make them responsive to previously nonpainful stimuli. Such “silent” nociceptors among our small Aδ and C fibers are normally unresponsive to stimuli—even destructive ones. Only after sensitization do they become responsive to mechanical or chemical stimuli and contribute greatly to hyperalgesia. For example, the neurotrophin nerve growth factor (NGF)—part of the inflammatory soup—triggers strong hypersensitivity to heat and mechanical stimuli by modulating TRPV1 channels. Activation of TRPA1 and ASICs are also important in hyperalgesia. The cytokine tumor necrosis factor-alpha (TNF-α) potentiates the inflammatory response directly and enhances release of substances that sensitize nociceptors. Drugs that interfere with neurotrophin and cytokine actions can be effective treatments for the pain of inflammatory diseases.

通过一种称为轴突反射的机制，动作电位可以沿着伤害性轴突从受伤部位传播到同一轴突的侧支中，支配皮肤的邻近区域。伤害感受器本身展开的轴突分支可能会释放使伤害感受末梢敏感的物质，并使它们对以前无痛的刺激做出反应。在我们的小 Aδ 和 C 纤维中，这种“沉默”的伤害感受器通常对刺激没有反应——即使是破坏性的刺激。只有在致敏后，它们才会对机械或化学刺激产生反应，并极大地导致痛觉过敏。例如，神经营养因子神经生长因子 （NGF） 是炎症汤的一部分，通过调节 TRPV1 通道触发对热和机械刺激的强烈超敏反应。TRPA1 和 ASIC 的激活在痛觉过敏中也很重要。细胞因子肿瘤坏死因子-α （TNF-α） 直接增强炎症反应并增强使伤害感受器敏感的物质的释放。干扰神经营养因子和细胞因子作用的药物可以有效治疗炎症性疾病的痛苦。

The cognitive sensations of pain are under remarkably potent control by the brain, more so than other sensory system. In some cases, nociceptors may fire wildly, although perceptions of pain are absent; on the other hand, pain may be crippling although nociceptors are silent. Chronic activation of nociceptors can lead to central sensitization, a chronic enhancement of central pain-processing circuits. Prolonged activity in nociceptive axons and their spinal cord synapses causes increased glutamate release, strong activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)– and NMDA (N-methyl-D-aspartate)–type glutamate receptors, and eventually a form of long-term potentiation (see pp. 329–337).

疼痛的认知感觉受到大脑非常有效的控制，比其他感觉系统更受控制。在某些情况下，伤害感受器可能会疯狂地发射，尽管没有对疼痛的感知;另一方面，尽管伤害感受器是无声的，但疼痛可能是严重的。伤害感受器的慢性激活可导致中枢敏化，这是中枢疼痛处理回路的慢性增强。伤害性轴突及其脊髓突触的长时间活动会导致谷氨酸释放增加，AMPA（α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）- 和 NMDA（N-甲基-D-天冬氨酸）型谷氨酸受体的强烈激活，并最终成为一种长期增强的形式（见第 329-337 页）。

Nonpainful sensory input and neural activity from various nuclei within the brain can modify pain. For example, pain evoked by activity in nociceptors (Aδ and C fibers) can be reduced by simultaneous activity in low-threshold mechanoreceptors (Aα and Aβ fibers). This phenomenon is a familiar experience—some of the discomfort of a burn, cut, or bruise can be relieved by gentle massage or rubbing (stimulating mechanoreceptors) around the injured area. In 1965, Melzack and Wall proposed that this phenomenon involves a circuit in the spinal cord that can “gate” the transmission of nociceptive information to the brain; control of the gate could be provided by other sensory information (e.g., tactile stimulation) or by descending control from the brain itself. Gate-like regulation of pain may arise from the modulation of gammaaminobutyric acid (GABA)–mediated and glycine-mediated inhibitory circuits in the spinal cord.

来自大脑内各种细胞核的非痛苦感觉输入和神经活动可以改变疼痛。例如，由伤害感受器（Aδ 和 C 纤维）的活动引起的疼痛可以通过低阈值机械感受器（Aα 和 Aβ 纤维）的活动来减轻。这种现象是一种熟悉的经历——一些烧伤、割伤或瘀伤的不适可以通过在受伤区域周围轻轻按摩或摩擦（刺激机械感受器）来缓解。1965 年，Melzack 和 Wall 提出，这种现象涉及脊髓中的一个回路，该回路可以“门控”伤害性信息向大脑的传输;门的控制可以由其他感觉信息（例如，触觉刺激）或通过大脑本身的下降控制来提供。疼痛的门样调节可能来自脊髓中 γ-氨基丁酸 （GABA） 介导和甘氨酸介导的抑制回路的调节。

A second mechanism for modifying the sensation of pain involves the relatively small peptides called endorphins. In the 1970s, it was discovered that a class of drugs called opioids (including morphine, heroin, and codeine) act by binding tightly and specifically to opioid receptors in the brain and, furthermore, that the brain itself manufactures “endogenous morphine-like substances,” collectively called endorphins (see p. 315).

改变疼痛感的第二种机制涉及称为内啡肽的相对较小的肽。在 1970 年代，人们发现一类称为阿片类药物（包括吗啡、海洛因和可待因）通过与大脑中的阿片受体紧密特异性结合而发挥作用，此外，大脑本身会产生“内源性吗啡样物质”，统称为内啡肽（见第 315 页）。

6 肌梭感知骨骼肌纤维长度的变化，而高尔基肌腱器官测量肌肉的力量

Muscle spindles sense changes in the length of skeletal muscle fibers, whereas Golgi tendon organs gauge the muscle’s force

The somatic sensory receptors described thus far provide information about the external environment. However, the body also needs detailed information about itself to know where each of its parts is in space, whether it is moving, and if so, in which direction and how fast. Proprioception provides this sense of self and serves two main purposes. First, knowledge of the positions of our limbs as they move helps us judge the identity of external objects. It is much easier to recognize an object if you can actively palpate it than if it is placed passively into your hand so that your skin is stimulated but you are not allowed to personally guide your fingers around it. Second, proprioceptive information is essential for accurately guiding many movements, especially while they are being learned.

到目前为止描述的躯体感觉受体提供关于外部环境的信息。然而，身体亦需要有关自身的详细信息，以了解它的每个部分在空间中的位置，它是否在移动，如果是，则向哪个方向移动，以及移动的速度。本体感觉提供了这种自我意识，并有两个主要目的。首先，了解我们四肢移动时的位置有助于我们判断外部物体的特征。如果您可以主动触诊一个物体，则比将其被动放在手中以刺激您的皮肤但不允许亲自引导手指绕过它要容易得多。其次，本体感觉信息对于准确指导许多动作至关重要，尤其是在学习它们时。

Skeletal muscles, which mediate voluntary movement, have two mechanosensitive proprioceptors: the muscle spindles (or stretch receptors) and Golgi tendon organs (Fig. 15-30). Muscle spindles measure the length and rate of stretch of the muscles, whereas the Golgi tendon organs gauge the force generated by a muscle by measuring the tension in its tendon. Together, they provide a full description of the dynamic state of each muscle. The different sensitivities of the spindle and the tendon organ are due partly to their structures but also to their placement: spindles are located in modified muscle fibers called intrafusal muscle fibers, which are aligned in parallel with the “ordinary” forcegenerating or extrafusal skeletal muscle fibers. On the other hand, Golgi tendon organs are aligned in series with the extrafusal fibers.

介导自主运动的骨骼肌有两个机械敏感的本体感受器：肌梭（或拉伸受体）和高尔基肌腱器官（图 15-30）。肌肉梭 (muscle spindles)测量肌肉的长度和拉伸率，而高尔基肌腱器官 (Golgi tendon organs)通过测量肌腱的张力来测量肌肉产生的力。它们共同提供了每块肌肉的动态状态的完整描述。纺锤体和肌腱器官的不同敏感性部分是由于它们的结构，但也是由于它们的位置：纺锤体位于称为导流内肌纤维的改良肌纤维中，它们与“普通”产生力或导流外骨骼肌纤维平行排列。另一方面，高尔基体肌腱器官与融合纤维串联排列。

The Golgi tendon organ consists of bare nerve endings of group Ib axons (see Table 12-1). These endings intimately invest an encapsulated collagen matrix and usually sit at the junction between skeletal muscle fibers and the tendon. When tension develops in the muscle as a result of either passive stretch or active contraction, the collagen fibers tend to squeeze and distort the mechanosensitive nerve endings, triggering them to fire action potentials.

高尔基体肌腱器官由 Ib 组轴突的裸露神经末梢组成（见表 12-1）。这些末端紧密地投入了一个封装的胶原蛋白基质，通常位于骨骼肌纤维和肌腱之间的交界处。当肌肉因被动拉伸或主动收缩而产生紧张时，胶原纤维往往会挤压和扭曲机械敏感的神经末梢，触发它们激发动作电位。

The mammalian muscle spindle is a complex of modified skeletal muscle fibers (intrafusal fibers) combined with both afferent and efferent innervation. The spindle does not contribute significant force generation to the muscle but serves a purely sensory function. A simplified summary of the muscle spindle is that it contains two kinds of intrafusal muscle fibers (bag and chain), with two kinds of sensory endings entwined about them (the primary and secondary endings). The different viscoelastic properties of the muscle fibers make them differentially sensitive to the consequences of muscle stretch. Because the primary sensory endings of group Ia axons coil around and strongly innervate individual bag muscle fibers (in addition to chain fibers), they are very sensitive to the dynamics of muscle length (i.e., changes in its length). The secondary sensory endings of group II axons mainly innervate the chain fibers and most accurately transduce the static length of the muscle; in other words, they are slowly adapting receptors. The discharge rate of afferent neurons increases when the whole muscle—and therefore the spindle—is stretched. ENaC and ASIC2 channels may contribute to the stretch sensitivity of the sensory nerve terminals in muscle spindles.

哺乳动物肌梭是改良骨骼肌纤维（导静脉内纤维）与传入神经支配和传出神经支配相结合的复合物。纺锤体不会对肌肉产生显着的力，但提供纯粹的感觉功能。肌肉梭的简化总结是它包含两种导静脉内肌纤维（袋和链），两种感觉末梢缠绕着它们（初级和次级末梢）。肌肉纤维的不同粘弹性特性使它们对肌肉拉伸的后果具有不同的敏感性。因为 Ia 组轴突的初级感觉末梢盘绕并强烈支配单个袋肌纤维（除了链纤维），所以它们对肌肉长度的动力学（即其长度的变化）非常敏感。II 组轴突的次级感觉末梢主要支配链纤维，最准确地转导肌肉的静态长度;换句话说，它们正在慢慢适应受体。当整个肌肉（以及纺锤体）被拉伸时，传入神经元的放电率会增加。ENaC 和 ASIC2 通道可能有助于肌肉梭感觉神经末梢的拉伸敏感性。

What is the function of the motor innervation of the muscle spindle? Consider what happens when the α motor neurons stimulate the force-generating extrafusal fibers and the muscle contracts. The spindle, connected in parallel to the extrafusal fibers, quickly tends to go slack, which makes it insensitive to further changes in length. To avoid this situation and to continue to maintain control over the sensitivity of the spindle, γ motor neurons cause the intrafusal muscle fibers to contract in parallel with the extrafusal fibers. This ability of the spindle’s intrafusal fibers to change their length as necessary greatly increases the range of lengths over which the spindle can work. It also means that the sensory responses of the spindle depend not only on the length of the whole muscle in which the spindle sits but also on the contractile state of its own intrafusal muscle fibers. Presumably, the ambiguity in this code is sorted out centrally by circuits that simultaneously keep track of the spindle’s sensory output and the activity of its motor nerve supply.

肌梭的运动神经支配有什么作用？考虑一下当 α 运动神经元刺激产生力的 EFFUSAL 纤维并且肌肉收缩时会发生什么。与纺纱外纤维并联的纺锤体很快就会变得松弛，这使得它对长度的进一步变化不敏感。为了避免这种情况并继续保持对纺锤体敏感性的控制，γ 运动神经元导致导膜内肌纤维与导膜外纤维平行收缩。纺锤体的导膜内纤维根据需要改变其长度的这种能力大大增加了纺锤体可以工作的长度范围。这也意味着纺锤体的感觉反应不仅取决于纺锤体所在的整块肌肉的长度，还取决于其自身导神经内肌纤维的收缩状态。据推测，这段代码中的歧义是由电路集中整理出来的，这些电路同时跟踪纺锤体的感觉输出和运动神经供应的活动。

In addition to the muscle receptors, various mechanoreceptors are found in the connective tissues of joints, especially within the capsules and ligaments. Many resemble Ruffini, Golgi, and Pacini end organs; others are free nerve endings. They respond to changes in the angle, direction, and velocity of movement in a joint. Most are rapidly adapting, which means that sensory information about a moving joint is rich. Nerves encoding the resting position of a joint are few. We are nevertheless quite good at judging the position of a joint, even with our eyes closed. It seems that information from joint receptors is combined with that from muscle spindles and Golgi tendon organs, and probably from cutaneous receptors as well, to estimate joint angle. Removal of one source of information can be compensated by use of the other sources. When an arthritic hip is replaced with a steel and plastic one, patients are still able to tell the angle between their thigh and their pelvis, even though all hip joint mechanoreceptors are long gone.

除了肌肉受体外，在关节的结缔组织中还发现了各种机械感受器，尤其是在关节囊和韧带内。许多类似于 Ruffini、Golgi 和 Pacini 终末器官；其他是游离神经末梢。它们对关节运动的角度、方向和速度的变化做出反应。大多数都在快速适应，这意味着关于活动关节的感觉信息非常丰富。编码关节静止位置的神经很少。尽管如此，我们还是很擅长判断关节的位置，即使我们闭着眼睛也是如此。似乎来自关节受体的信息与来自肌肉梭和高尔基肌腱器官的信息相结合，也可能来自皮肤受体的信息相结合，以估计关节角度。删除一个信息来源可以通过使用其他来源来补偿。当关节炎髋关节被钢制和塑料髋关节取代时，即使所有的髋关节机械感受器早已消失，患者仍然能够分辨出大腿和骨盆之间的角度。

7 Reference

• Physiology
• Pharmacology
• Addiction
• BBB 血脑屏障概述

• Smith et al. Insights into inner ear function and disease through novel visualizatio of the ductus reuniens, a semila communication between hearing and balance mechanisms. JARO (2022)
• http://www.cochlea.eu/en/cochlea
• http://www.cochlea.eu/en/cochlea/cochlear-fluids