Mechanoreception and Nociception Primer (1) PDF

SENSORY PHYSIOLOGY During these lectures, we will be learning about how sensory information is sensed, conveyed, and processed by the body. Somatosensory processing includes a host of different sensory systems including those that are both consciously and subconsciously driven. Sensory systems where...

SENSORY PHYSIOLOGY During these lectures, we will be learning about how sensory information is sensed, conveyed, and processed by the body. Somatosensory processing includes a host of different sensory systems including those that are both consciously and subconsciously driven. Sensory systems where we have a conscious awareness (or perception) refer to our special senses (e.g., vision, hearing, taste, smell, and equilibrium) and our somatic senses (e.g., touch, temperature, pain, and propioception). Subconsciously driven somatosensory systems include again somatic stimuli (e.g. muscle tension/length and propioception) and stimuli associated with our visceral organs (e.g., blood pressure, GI tract distension, body temperature, lung inflation, etc.). All of these stimuli combined give us a thorough representation of the state of our internal and external environments and allow for the comparison against biological set points and integration of responses from higher brain centers. SOMATOSENSORY SYSTEM OVERVIEW The somatosensory system has two major components: a system that detects mechanical stimuli and another system for the detection of painful stimuli and changes in temperature. Somatosensory information is sensed by a variety of receptors that convey information to the brain via ascending pathways, ultimately projecting towards the primary somatosensory cortex and higher order association cortices (to be discussed later). Sensory receptors are divided into three groups based on their function: (1) Mechanoreceptors – sensing mechanical deformation (2) Nociceptors – sensing painful stimuli (3) Thermoceptors – sensing changes in temperature The table on the following page provides examples of these different types of sensory receptors. Receptors boxed in red (free nerve endings) refer to nociceptors and thermoceptors. Receptors boxed by blue correspond to mechanosensory receptors (individual types to be discussed later), while the receptors boxed in green represent propioceptors (sensing change in body position; to be discussed later). These receptors are also classified by their morphology, as referenced in the above table: (1) Free nerve endings- highly branched and unmyelinated structures that are essentially the free end of an axon (2) Encapsulated endings – contain surrounding capsule structures that change the response characteristics of the nerves Most free nerve endings are responsible for sensing pain and temperature stimuli while encapsulated receptor endings are responsible for detecting tactile (touch) information. How do these receptors work? Despite the differences in the types of endings, somatosensory afferent receptors work predominantly in the same way. A stimulus must be sensed by the receptor, ultimately leading to a change in ionic permeability of the receptor cell membrane. From what we understand from previous lectures, changes to the ionic permeability of a membrane have the ability to generate a depolarizing potential in the nerve ending (recall your receptor generator potential of the pacinian corpuscle from Dr. Clausen’s lectures) that is capable of eliciting an action potential. The overall action is the conversion of the energy of the stimulus into an electrical signal in the sensory neuron. Quality vs. Quantity of a Stimulus It should be clear to you that not every stimulus that encounters your body is perceived in the same way. For example, some stimuli hurt more than others while other stimuli create different durations of stimulation. In order to understand how different stimuli can create different perceptions of pain, touch, temperature, etc., it becomes important to understand how we classify these stimuli with regards to quantity and quality. Quality – refers to what the stimulus represents and what the stimulus is, and is determined by the relevant receptors and the location of their central targets Quantity – refers to the rate of action potential discharge triggered by the receptor potential Both of these concepts can be explained by the dynamic or static properties of a stimulus also. For example, some stimuli act on receptors that produce a train of action potentials that can persist over a period of time while other stimuli act on receptors that have an initial response, but then limit their action potential production. These receptors are classified as slowly adapting and rapidly adapting receptors. Slowly adapting receptors (tonic) – continue to fire as long as the stimulus is present Rapidly adapting receptors (phasic) – fire initially with the presence of a stimulus, but become quiescent before the stimulus is removed MECHANOSENSORY INFORMATION Mechanosensory receptors are specialized to receive tactile information. These receptors are generally found in the cutaneous and subcutaneous tissues and each encodes subtlety different tactile information. They also differ with regards to their ability to act as phasic or tonic receptors. Initially though, you might be curious as to what is considered tactile information. Tactile information is classified as information that represents touch, pressure, vibration, and cutaneous tension and there are specialized mechanosensory receptors that excel at identifying these individual stimuli. The four major types of these receptors (which exhibit both low threshold and high sensitivity) are: meissner’s corpuscles, pacinian corpuscles, merkel’s disks, and ruffini corpuscles. They can be identified within different layers of the epidermal, dermal, and subdermal tissue in the diagram below. Dynamic Quality Receptors Meissner’s corpuscles are receptors specialized to respond to changes in texture. They are located just beneath the epidermis and act as rapidly adapting receptors. Because of their ability to sense low-frequency vibrations, these receptors are ideal candidates to detect textural changes. These receptors have a dense population within the hand, where their highest density is found on the fingers and palms, and account for about 40% of the sensory innervation of the hand. They also are found on the soles of the feet. Pacinian corpuscles are receptors that are found in subcutaneous tissues of the hand and discriminate fine surface textures (predominantly as a result of their ability to sense high frequency vibrations between 250-350 Hz). They represent about 10-15% of the cutaneous receptors of the hand and like meissner corpuscles, are rapidly adapting. As you have learned previously, these corpuscles contain an onion like capsule that responds to changes in pressure, creating graded potentials that can be translated into action potentials. Static Quality Receptors Merkel’s disks provide information about light and steady pressure. In this way, they act as tonic receptors (slowly-adapting). They are located within the epidermis and account for 25% of the mechanosensory receptors on the hand. These receptors allow for the static discrimination of shapes, edges, and rough textures. Ruffini’s corpuscles provide information regarding cutaneous stretch or tension and are located deep within the skin, ligaments, and tendons. They generally orient themselves in positions parallel to stretch lines within the skin to better identify cutaneous tension, although there is a limited understanding of the exact mechanisms of how these receptors function. However, these receptors provide insight into static qualities of a stimulus and are therefore categorized as tonic (slowly-adapting). Mechanosensory Discrimination The ability to accurately detect tactile stimuli varies depending on the region of the body it is applied to. For example, most people would agree that our fingertips or lips are far more sensitive to tactile information than our lower back or thigh. This is supported by experiments that measure tactile stimulation and the ability to detect the stimulation across different regions of the body, called the twopoint discrimination task. This task measures the minimal inter-stimulus distance required to perceive two simultaneously applied stimuli as distinct and gives us insight into receptive fields of somatosensory neurons. The two point discrimination task demonstrates that the areas of the body that are most sensitive to tactile stimuli (and therefore have small distances between two simultaneous stimuli that they can detect) are the hands/fingers, areas of the face, and feet. This regional difference is a consequence of the density of these receptors and the receptive field of the somatosensory neuron. What is a receptive field? A receptive field of a somatosensory neuron is the region of skin within which a tactile stimulus evokes a sensory response in the cell or its axon. Large receptive fields give you little insight into the precise location of the stimulus, whereas smaller receptive fields give you a quite detailed stimulus location. Receptive field properties change regionally across the body allowing for different responses to tactile stimulation. Receptive fields of sensory afferent neurons are also capable of overlap. The overlap of these receptive fields allows for the convergence of primary sensory neurons that contain sub-threshold stimuli to sum at a secondary sensory neuron and initiate an action potential. MECHANOSENSORY RECEPTORS SPECIALIZED FOR PROPIOCEPTION Propioceptors (‘receptors for self’) provide detailed and continuous information about the position of the limbs and other body parts in space. Essentially, this is information about mechanical forces that arise from the body itself. These propioceptors are generally low-threshold mechanoreceptors such as muscle spindles, golgi tendon organs, and joint receptors that allow for the accurate performance of complex movements. Let’s consider the example of a muscle spindle to provide insight into how a propioceptor might function. You’ve already learned the muscle spindles are found within most striated (skeletal) muscles. They consist of intrafusal fibers that are surrounded by connective tissue and are distributed throughout the muscle in a parallel arrangement to skeletal muscle fibers. They have two components: nuclear bag fibers and nuclear chain fibers, both of which are innervated by sensory Ia axons which create primary sensory endings. The contraction of the muscle allows for the sensory endings to convey information about muscle length. The number of muscle spindles is correlated to the type of movement and muscle will make. Coarse movements, like those observed by moving a leg or the arm, require less muscle spindle action than that of the eye, where ocular movements need to be precise in order to maintain or change gaze. MECHANOSENSORY AND PROPIOCEPTIVE PATHWAYS Action potentials created by mechanosensory stimuli are conveyed to the CNS through afferent sensory axons in the peripheral nerves. Their neuronal cell bodies are located within the dorsal root ganglia which project short axonal projections onto the dorsolateral spinal cord region via the dorsal (or sensory) roots. These sensory afferent neurons are also referred to as first order neurons. Within the spinal cord, information regarding tactile and proprioceptive stimuli from these neurons is carried to the brain via the dorsal column-medial lemniscus pathway. The major branch of sensory incoming axons into the dorsal horn ascends ipsilaterally (on the same side of the spinal cord) to synapse onto second order neurons in the lower medulla. These second order neurons form the internal arcuate tract which subsequently crosses the midline (decussates) to form the medial lemniscus tract. This tract ascends toward the somatosensory portions of the thalamus where it synapses onto third order neurons and ultimately projects to the primary somatosensory cortex. The Trigeminal Portion of the Mechanosensory System The pathway described above carries mechanosensory and proprioceptive information from the upper and lower body, leaving a pathway to be required to facilitate tactile and proprioceptive information transfer from the face. This sort of information is transmitted to the CNS via the trigeminal somatic sensory system, where the peripheral processes of these neurons form three main subdivisions of the trigeminal nerve. Distinct branches of the trigeminal nerve innervate a well-defined region of the face. (1) Opthalmic (2) Maxillary (3) Mandibular The sensory roots of these branches of the trigeminal nerve enter the brainstem at the pontine level and synapse onto neurons within a region called the trigeminal brainstem complex. The trigeminal brainstem complex consists of two distinct nuclei. (1) Principle nucleus – processing of mechanosensory stimuli (2) Spinal nucleus – processing of painful and thermal stimuli Second order neurons within these distinct nuclei cross the midline to join the medial lemniscus pathway that continue upwards towards the ventral posterior nucleus of the thalamus via the trigeminothalamic tract. THE THALAMUS AND SOMATOSENSATION Mechanosensory and proprioceptive information ascending from the spinal cord and brainstem regions pass through the ventral posterior complex of the thalamus. Ventral posterior lateral thalamus – receives projections from the medial leminscus pathway carrying information from the body and posterior head Ventral posterior medial thalamus – receives information from the trigeminal leminscus (pain/temperature and mechanosensory from the face) pathway. THE SOMATOSENSORY CORTEX Axons ascending through the ventral lateral and medial thalamic structures project to cortical neurons of the somatosensory cortex, a region located in the post central gyrus of the parietal lobe. The human somatosensory is divided into four regions. These include Broadman’s areas: 3a – proprioceptive stimuli 3b – cutaneous stimuli 1 – cutaneous stimuli 2–tactile and proprioceptive stimuli In these different regions, somatotopic maps exist to map the regions of the body to be represented in a medial to lateral arrangement. It should also begin to be apparent from the figure above, that the regions of the body aren’t represented in relation to their size. In fact, body regions where manipulation and sensation are extremely important are governed by larger cortical domains. HIGHER ORDER CORTICAL REPRESENTATION The primary somatosensory cortex is not the final destination of sensory information. From the somatosensory cortex, information is distributed to higher cortical centers and to association cortices (also called secondary somatosensory cortical regions). It is within these regions that the sensory information is integrated reciprocally with emotional cues from limbic structures and executive input from the frontal lobe structures. This integration allows for the learning and memory associated with different sensory stimuli experiences. THERMOCEPTION Receptors that sense temperature within normal cold and warm ranges (ranges that do not produce a painful sensation) are referred to as thermoceptors. Thermoreceptors exist in two forms, but both forms are characterized by unmyelinated free nerve endings that terminate in the subcutaneous layers of the skin: 1. Cold receptors – sensitive primarily to temperatures lower than body temperature 2. Warm receptors – sensitive to temperatures between the range of 37° C to 45° C Thermoreceptors are slowly-adapting and are found across the body, though cold receptors are present in greater numbers and densities than warm receptors. NOCICEPTION Nociceptors exist to protect our body from noxious (harsh) stimuli. In this way, they can alert the body of stimuli in order to prevent tissue damage. Similar to thermoceptors, nociceptors are generally unmyelinated free nerve endings that are located within the subcutaneous layer of skin, however, they are less specific than thermoceptors in that they respond to a variety of painful stimuli including chemical, mechanical, and thermal. Additionally, whereas thermoreceptors are tonically active and display changes in action potential frequency only with changes to temperature within a normal range, nociceptors are phasic receptors in that they initiate firing with the introduction of a given painful stimulus. However, unlike typical phasic receptors, their firing continues to increase with the increasing intensity of the painful stimulus. There are three distinct classes of nociceptors in the skin 1. 2. 3. Polymodal C fibers thinly/lightly myelinated and fast-conducting (20 ms/s) and are sensitive only to mechanical or thermal stimuli. Polymodal receptors have the ability to respond to thermal, mechanical, and chemical stimuli and are unmyelinated, resulting in much slower conduction velocities (2 m/s). The receptive fields of the afferent sensory neurons ending in these nociceptors (for all three types) are quite large, as it is apparently more important to be able to detect a painful stimulation then to know where the precise localization of that stimulus is on the body. First pain vs. second pain Two general categories of pain perception exist: 1. First pain – sharp and localized 2. Second pain – delayed and diffuse creates a rapid and intense sensation. If the intensity of the painful stimulus is increased further, the more slowly conducting C fibers will be activated to generate a duller and more long-lasting sensation of pain. The figure below in (A) describes the fiber types and the subjective pain intensity when they are stimulated. The remaining panels of this figure describe experiments that demonstrated that the two distinct fiber types were ibers were selectively blocked and sharp pain was eliminated while diffuse pain continued to persist. In (C), the opposite case is observed, where the elimination of C fibers results in the elimination of persisting dull pain intensity. Gate Control Theory of Pain Pathways that carry sensory information from the free nerve terminal endings to the brain utilize ascending pain pathways (to be discussed in detail later). These pathways enable a cortical or perceptual experience of pain that can also be integrated and modified by emotional (limbic) pathways. However, the transmission of pain combined with somatosensory afferent input can also modify pain perception, which is referred to as gate control theory. In the absence of input from C fibers, tonically active inhibitory interneurons within the dorsal horn of the spinal cord suppress the pain pathways, leading to no transmission of pain signals to the brain. However, upon the introduction of strong painful stimuli, C fibers transmit information to these interneurons, stopping their inhibition. This allows for strong signals regarding the painful stimulus to be reached by the brain. Interestingly though, when tactile and painful stimulation are combined, pain perception can be modified. This is explained by the simultaneous somatosensory and nociceptive input acting on these interneurons. The result of this is a parallel inhibition of the ascending pain pathway so that pain perception by the brain is lessened. Central Pain Pathways The pathway that conveys painful sensory stimuli have two components: 1. Discriminative – determines location, intensity, and quality of stimulus 2. Affective-Motivational – signals the unpleasant quality of the experience and enables autonomic nervous system responses The discriminative pathways for the transmission of nociceptive information are divided into a pathway that corresponds to the upper/lower body (the spinothalamic system or anterolateral system) and a pathway that corresponds to noxious and thermal stimulation of the face (the trigeminal pain and temperature system). In the spinothalamic system, noxious pain and temperature information enter the dorsal horn of the spinal cord via the dorsal root ganglion. These sensory afferents synapse onto second order neurons which cross the midline and ascend to the brainstem and thalamus. The principal target of the spinothalamic pathway is the ventral posterior lateral nucleus of the thalamus. The third order neurons within this thalamic region send projections to the primary and secondary somatosensory cortex for processing. In the trigeminal pain and temperature system, first order neurons carry sensory information from facial nociceptors and thermoceptors into the brainstem at the level of the pons. These fibers descend to the medulla and form the spinal trigeminal tract, ultimately synapsing onto nuclei of the spinal trigeminal complex. These second order axons cross the midline and ascend to the thalamus. Nocieptive and temperature information synapses onto third order neurons within the ventral posterior medial nucleus. These third order neurons send projections to the primary and secondary somatosensory cortex for processing. The pathway that mediates the affective-motivational aspects of pain utilizes a similar pathway to that described for the lower/upper body nociception. However, separate projections exist from the anterolateral tract that allow for affective and executive processing. These occur in three distinct regions: 1. The middle medulla to form synapses within the reticular formation 2. The mid-pontine region to synapse onto the nuclei which communicate with amygdala and hypothalamic structures 3. The nuclei of the thalamus to synapse onto regions within the cingulated cortex Referred Pain Referred pain is a consequence of the body having minimal neurons in the dorsal horn of the spinal cord that are specialized solely for the transmission of visceral (organ) pain. Therefore, visceral pain is generally poorly localized and may be felt in areas that are far removed from the actual stimulus or insult. The poor localization is a result of having multiple primary sensory neurons converging onto a single ascending tract in the spinal cord. In the example below, pain signals from the skin are more common than pain from internal organs, and the brain associates activation of the pathway with pain in the skin. SENSORY FUNCTION There are two basic forms of sensory systems. These are contact and distant, and the contact form refers to olfactory (smell) sensations and gustatory (taste) sensations. Smell and taste, as sensory systems, are collectively known as the chemical senses. It is also important to understand that special senses can be divided into two major classes based on the interaction of receptor and stimulant. These classes are non-invasive and invasive. The chemical senses are invasive senses in that the ligand (the tastant molecule or volatile compound) interacts directly with membrane receptors. Other specialized senses including vision, hearing, and equilibrium are noninvasive. These non-invasive senses will be discussed in greater detail in future lectures. You might wonder what the importance of the chemical senses are. Why do we require the ability to screen soluble and airborne molecules via the gustatory and olfactory systems, respectively? Well, we need to be able to decipher the relative safety of molecules that are being ingested or inhaled, a product of the receptors and the pathways they innervate. Chemicals in nature also provide an important source of information for all animals because they have the ability to affect behaviors such as feeding, mating, and territoriality.