Pain | Lecture Notes PDF

Pain Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Initially, when experiencing pain resulting from trauma, the person will try to withdraw from the stimulus. Muscle guarding occurs as the body’s way to immobilize the inju...

Pain Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Initially, when experiencing pain resulting from trauma, the person will try to withdraw from the stimulus. Muscle guarding occurs as the body’s way to immobilize the injured area and prevent further damage (Fig. 1). This reaction of the muscles requires a high level of metabolic activity at the same time as it compresses the blood vessels. The compromised circulation is often inadequate to supply metabolic needs, leading to ischemia, local anemia due to mechanical obstruction of the blood supply. This ischemia becomes a new source of pain. In addition, the compromised circulation impedes the removal of the metabolic wastes, many of which sensitize nociceptors, resulting in further enhancement of pain.  Fig.1: Primary pain cycle and associated internal changes. (From Mannheimer, JS, and Lampe, GN, eds. Clinical Transcutaneous Electrical Nerve Stimulation. FA Davis, Philadelphia, 1984, p 10 Classification of pain: According to duration: Acute pain is short term and resolves within 3months. It is the body’s response to a specific injury or trauma, and it serves a biological purpose. The most important feature of acute pain is that it is self- limiting; resolution of pain occurs with tissue healing or repair. In some cases, however, acute pain may undergo transition to chronic pain. Chronic pain is pain that lasts longer than 3 months persisting beyond the normal time of healing and leads to a long-term loss of function, as well as imposing many psychosocial stresses on the patient and his or her friends and family. Episodic or recurrent pain: Occurs intermittently over a long period of time and the patient can be pain free in-between episodes (e.g. sickle cell disease). According to mechanism (the kind of damage that causes pain). Nociceptive pain: when body tissues are injured or damaged that stimulates pain receptors called nociceptors. It is further classified into somatic or visceral pain: 1) Somatic pain: caused by stimulation of nociceptors in superficial tissues (e.g. skin and mucosa), usually well-localized, sharp or burning in nature and not referred. Also deep tissues (e.g. bone, joints and muscles), usually well localized and dull or aching in nature and can be referred to skin. 2) Visceral pain: caused by stimulation of nociceptors in the viscera (e.g. internal abdominal organs). Usually poorly localized, diffuse and dull, aching or cramping in nature. This pain can be referred to skin parts supplied by the same sensory roots as the diseased organ. Referred pain is Pain arising from deep body structures but felt at another, distant site is called referred pain Mechanisms that cause the referral of pain are based on the convergence of cutaneous (skin) and visceral (internal organ) afferent nerve fibers within the spinal cord. These areas may overlie each other, complicating the diagnostic process. Referred pain may be an indicator of the spinal segment  in which there is a problem. Pain in the L5 dermatome (buttock, leg, and foot) could arise from irritation around the L5 nerve root, the L5 disc, any facet involvement of L4 to L5, any muscle supplied by the L5 nerve root, or any visceral structure having L5 innervation. Another common example of referred pain is the pain associated with angina (ischemia of the heart) and with myocardial infarction (heart attack). An individual experiencing these conditions may feel pain radiating down the arm in the T1 and T2 dermatomes. Pain is felt here because the pain fibers innervating the heart arise from the T1 to T5 nerve roots (Fig. 2). Dermatomes: Areas of skin that are innervated by a particular nerve root. Sclerotomes: Areas of bone that are innervated by a specific nerve root, and myotomes: are the areas of muscle innervated by a nerve root.  Diagram of dermatomes. When someone is experiencing a “heart attack,” pain can be perceived throughout the left upper extremity, which corresponds to the overlap of dermatome, myotome, and scleratome. (Adapted from Mannheimer, JS, and Lampe, GN, eds. Clinical Transcutaneous Electrical Nerve Stimulation. FA Davis, Philadelphia, 1984, p 109.) Neuropathic pain: Caused by injury to nerve cells in the peripheral or central nervous system. Some common sensory features associated with neuropathic pain include allodynia, hyperalgesia, hypoalgesia, paresthesia and dysesthesia. Pain is usually poorly localized and diffuse. It is describes as needles, tingling, burning, sharp or shooting in nature.  Diseases such as diabetes can damage nerves. Or an injury can damage them. Certain chemotherapy drugs may cause nerve damage. Nerves can also be damaged by a stroke. Psychogenic pain: Which is pain that is affected by psychological factors. Psychogenic pain most often has physical origin either in tissue damage or nerve damage. But the pain gets worse or lasts longer because of things like fear, depression, stress, or anxiety. In some cases, pain comes from a psychological condition. Neural transmission: Painful stimuli mechanical (pressure, pinch), heat, and chemical. Afferent nerve fibers transmit impulses from the sensory receptors toward the brain while efferent fibers, such as motor neurons, transmit impulses from the brain toward the periphery. First-order or primary afferents transmit the impulses from the sensory receptor to the dorsal horn of the spinal cord (Aδ and C fibers). Second-order afferent fibers carry sensory messages up the spinal cord to the brain. They receive input only from Aδ and C fibers. All of these neurons synapse with third-order neurons, which carry information to various brain centers where the input is integrated, interpreted, and acted upon.  Neural afferent transmission. Sensory (pain) information from free nerve endings is transmitted to the sensory cortex in the brain via first-, second-, and third-order neurons. Pain Perception: Three types of stimuli can activate pain receptors in peripheral tissues: mechanical (pressure, pinch), heat, and chemical. Pain is initiated when there is injury to a cell causing a release of three chemicals, substance P, prostaglandin, and leukotrienes, which sensitize the nociceptors in and around the area of injury by lowering their depolarization threshold. This is referred to as primary hyperalgesia, in which the nerve’s threshold to noxious stimuli is lowered, thus enhancing the pain response. Over a period of several hours secondary hyperalgesia occurs, as chemicals spread throughout the surrounding tissues, increasing the size of the painful area and creating hypersensitivity.  Peripheral sensitization of pain fibers. First-order neuron: Pain receptors: Specialized receptors called nociceptors signal actual or potential tissue damage. The nociceptors are actually three distinct types of free nerve endings that respond to different stimulus modalities (Table1). The nociceptors do not normally respond to sensory stimuli in nondamaging ranges. Table 1: types of nociceptors  The nociceptive message is transmitted from the periphery to the central nervous system by the axon of the primary afferent nociceptor. This neuron has its cell body in the dorsal root ganglion and a long process, the axon, that divides and sends one branch out to the periphery and one into the spinal cord. The primary afferent nociceptor Nociceptors initiate electrical impulses along two afferent fibers toward the spinal cord. Aδ and C fibers transmit sensations of pain and temperature from peripheral nociceptors. The majority of the fibers are C fibers. Aδ fibers are myelinated large diameter fibers with fast conduction velocities. It transmits acute pain. Acute pain is sharp, localized and short, lasting only as long as there is a stimulus, such as the initial pain of an unexpected pinprick. Aδ-fibers are also the smallest myelinated nerves and have a relatively fast conduction velocity of 30 m/s. The diameter of Aδ-fibers is about 2–5 µm and is responsive towards short-lasting and pricking pain. C fibers are unmyelinated afferent neurons and originates from both superficial skin tissue and deeper ligament and muscle tissue. It transmits chronic pain. This pain is an aching, throbbing, or burning sensation that is poorly localized and less specifically related to the stimulus. There is a delay in the perception of pain following injury, but the pain will continue long after the noxious stimulus is removed. C-fibers nociceptors are polymodal, unmyelinated neurons. This lack of myelination is the cause of their slow conduction velocity, which is on the order of no more than 2 m/s. C fibers are on average 0.2– 1.5 μm in diameter. They are activated by thermal, mechanical and chemical stimuli. The activation of C-fibers is from poorly localized stimuli, such as burning sensation of the skin. Second-order neuron: Primary afferent nociceptors transmit impulses into the spinal cord dorsal horn. Bror Rexed (1950s) identified layers, or laminae, within the grey matter of the dorsal horn of the spinal cord where cells were grouped according to their structure and function, rather than solely on location. In the spinal cord, the primary afferent nociceptors terminate near second-order nerve cells in the dorsal horn of gray matter. Some Aδ and most C afferent neurons enter the spinal cord through the dorsal horn of the spinal cord and synapse in the substantia gelatinosa with a second- order neuron. The primary afferent nociceptors release chemical transmitter substances from their spinal terminals i.e. substance p. “The dorsal horn of the spinal cord acts like a computer that processes the incoming sensory signals rearranging and modulating them before sending them on to the next higher level.” Within the dorsal horn, A-delta and C fibers communicate with several different types of neurons in different layers of the gray matter. These include nociceptive-specific neurons that receive input only from A-delta and C fiber (pain fibers) and wide-dynamic-range neurons that receive input from A- beta mechanoreceptive (nonpainful) fiber as well as from A-delta and C fibers. Nociceptive-specific neurons assist in discrimination of the specific type of pain that is, thermal, mechanical, or chemical, but do not localize the pain sensation well. The wide-dynamic-range cells contribute to the localization of burning or pricking pain as well as the discrimination between touch and noxious pinching. These cells receive input from both the viscera and the skin. It is thought that this convergence of noxious stimuli may be the basis for referred pain, because the brain may be unable to discriminate between a visceral and a cutaneous source of stimuli. Wide-dynamic-range cells are also called T (transmission) cells that were proposed to be in the substantia gelatinosa of the dorsal horn of the spinal cord and form the basis for the gate control theory. The axons of some of these second-order cells cross over to the opposite side of the spinal cord and project for long distances to the brain stem and thalamus. The pathway for pain transmission lies in the anterolateral quadrant of the spinal cord. There are two major targets for ascending nociceptive axons in the anterolateral quadrant of the spinal cord: the thalamus and the medial reticular formation of the brain stem. PAIN PATHWAYS Ascending For an individual to be aware of pain, the noxious input to the dorsal horn of the spinal cord must travel to the brain. Several ascending tracts are responsible for the transmission of pain signals: Neospinothalamic pain pathway:  The axons of most of the transmission cells cross over and ascend via the spinothalamic tract. This tract transmits the pain signal to the thalamus. The thalamus acts as a general relay station for sensory information and has precise projections to the portion of the brain called the somatosensory cortex. Once the signal reaches the cortex, it is perceived as a sharp, discriminative, and relatively localized sensation. Paleospinothalamic Pathway: The second pathway is called the spinoreticulothalamic pathway. As the name implies, signals travel from the spine to the reticular formation of the brainstem and to the thalamus. Signals are also thought to connect to nuclei in the periaqueductal gray area of the midbrain and to areas of the limbic system. The information that this pathway conveys is perceived as diffuse poorly localized somatic and visceral pain. Slow pain always keeps a person awake. The pathway evokes the emotional experience of pain and mediates autonomic responses. N.B. In the midbrain, the reticular formation plays a key role in wakefulness. It consists of a network of neurons that extend throughout the brainstem and help regulate arousal and attention. When the reticular formation is activated, it increases alertness and promotes wakefulness. N.B. The periaqueductal gray (PAG) is a key structure in the propagation and modulation of pain, sympathetic responses as well as the learning and action of defensive and aversive behaviors. N.B. Limbic system is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain. The structures and interacting areas of the limbic system are involved in motivation, emotion, learning, and memory. The limbic system is where the subcortical structures meet the cerebral cortex. "Gate control" theory:  Ronald Melzack and Patrick Wall introduced their "gate control" theory of pain in the 1965 Science article "Pain Mechanisms: A New Theory". The authors proposed that both thin (pain) and large diameter (touch, pressure, vibration) nerve fibers carry information from the site of injury to two destinations in the spinal cord: Transmission cells that carry the pain signal up to the brain, and inhibitory interneurons that impede transmission cell activity. Activity in both thin and large diameter fibers excites transmission cells. Thin fiber activity impedes the inhibitory cells (tending to allow the transmission cell to fire) and large diameter fiber activity excites the inhibitory cells (tending to inhibit transmission cell activity). So, the more large fiber (touch, pressure, vibration) activity relative to thin fiber activity at the inhibitory cell, the less pain is felt. The authors had drawn a neural "circuit diagram" to explain why we rub a smack. They pictured not only a signal traveling from the site of injury to the inhibitory and transmission cells and up the spinal cord to the brain, but also a signal traveling from the site of injury directly up the cord to the brain (bypassing the inhibitory and transmission cells) where, depending on the state of the brain, it may trigger a signal back down the spinal cord to modulate inhibitory cell activity (and so pain intensity). The theory offered a physiological explanation for the previously observed effect of psychology on pain perception. The firing of the transmission neuron determines pain. The inhibitory interneuron decreases the chances that the transmission neuron will fire. Firing of C fibers inhibits the inhibitory interneuron (indirectly), increasing the chances that the transmission neuron will fire. Firing of the Aβ fibers activates the inhibitory interneuron, reducing the chances that the projection neuron will fire, even in the presence of a firing nociceptive fiber. Descending Pain Control (endogenous opiate theory): Emotions (such as anger, fear, stress), previous experiences, sensory perceptions, and other factors coming from the thalamus in the cerebrum stimulate the periaqueductal grey (PAG) matter of the midbrain. The pathway over which this pain reduction takes place is a dorsal lateral projection from cells in the PAG to an area in the medulla of the brain stem called the raphe nucleus. When the PAG fires, the raphe nucleus also fires. Serotonergic efferent pathways from the raphe nucleus project to the dorsal horn along the entire length of the spinal cord where they synapse with enkephalin interneurons located in the substantia gelitanosa. The activation of enkephalin interneuron synapses by serotonin suppresses the release of the neurotransmitter substance P from Aδ and C fibers used by the sensory neurons involved in the perception of chronic and/or intense pain. Additionally, enkephalin is released into the synapse between the enkephalin interneuron and the second-order neuron that inhibits synaptic transmission of impulses from incoming Aδ and C fibers to the second-order afferent neurons that transmit the pain signal up the lateral spinothalamic tract to the thalamus