Exam 4 Quiz gecko.docx

Define the following and identify the areas where each occurs: - **Transduction** = heat, cold, mechanical distortion is sensed by receptor and then converted into electrical impulses - **Transmission** = conduction of electrical impulses through the dorsal horn and thalamus to the hig...

Define the following and identify the areas where each occurs: - **Transduction** = heat, cold, mechanical distortion is sensed by receptor and then converted into electrical impulses - **Transmission** = conduction of electrical impulses through the dorsal horn and thalamus to the higher brain centers - **Modulation** = inhibitory or excitatory alteration of the pain transmission - Modulation occurs before movement to cerebral cortex for perception of pain - **Perception** = thalamus acts as the relay station for signals traveling to the somatosensory cortex - Thalamus is the site of conscious pain Identify fiber types - **C fibers** respond to heat and sustained pressure - **A fibers** - Type 1 (A-b) respond to heat, mechanical, and chemical stimulation (i.e. polymodal) - Type 2 (A-d) respond only to heat Nociceptor Sensitization = nociceptor fires at a lower level of stimulation resulting in an exaggerated response or spontaneous firing - Nociceptors are normally at rest - Inflammatory cells then release cytokines potentiating nociceptor responses & leading to sensitization - Sensitization leads to transition from acute to chronic pain when inflammatory processes do not resolve - **Hyperalgesia = increased pain sensations to painful stimuli** - **Primary hyperalgesia** = occurs at the site of injury and is the result of increased sensitivity to nociceptors at the injury site - **Secondary hyperalgesia** = manifested at the uninjured skin surrounding the original injury (mechanical stimuli only) - Pain increased by facilitating nociceptor signal transmission - Can occur as a result of windup - **Allodynia = perception of pain from normally non-painful stimuli** Peripheral inflammation and nerve injury can cause central sensitization in the dorsal horn neurons, which can cause chronic pain Discuss the manifestations and causes of Windup - Windup is a type of sensitization where repeated, low frequency stimulation of pain pathways leads to an increased response to pain due to increased excitability of neurons in the spinal cord which process pain signals -- pain sensation is amplified with minor or moderate stimuli causing chronic pain - Causes = accumulation of glutamate and substance P causing prolonged activation of NMDA receptors and therefore increased excitability of the dorsal horn neurons - Heterosynaptic activity-dependent plasticity is a type of sensitization where after a period of intense stimulus, normally subthreshold stimulus causes activation - Pain synapse undergoes intense stimulation - Stimulation ends, but surrounded receptors are plastic and therefore more sensitized to pain - Subthreshold stimulus occurs and other pain synapses are activated causing amplification and spreading of pain Difference between hyperalgesia and heterosynaptic activity dependent plasticity - Hyperalgesia is a normal and adaptive response to protect from further injury - Heterosynaptic activity dependent plasticity is an abnormal and maladaptive response Differentiate substances contributing to nociceptor sensitization and other neurotransmitters - **Direct activators** contribute to pain by **activating actual receptor i.e. nociceptors** and/or inducing the sensitization of the nociceptor response to painful stimuli - **Indirect activators activate the inflammatory cells to release cytokines** to induce **primary hyperalgesia** - **Cytokines** are **both direct and indirect activators** of nociceptor sensitization - Direct activators = bradykinin, protons, prostaglandin E, purines - Indirect activators = serotonin, histamine, arachidonic acid metabolites Identify the role of the following in CNS pain physiology - Spinal dorsal horn = relay center for nociception - Superficial dorsal horn (lamina I and II) serve as the main target for C fibers - Lamina V is the site of wide dynamic range neurons, which play a role in perception in pain intensity and modulation of pain signals - Wide range because it receives input from A-d and C fibers - Convergence of A-d and C fibers allow integration of different types of sensory information - Somatosensory cortices (i.e. S1 and S2) in the forebrain = process where the pain is coming from and how intense it is - Anterior cingulate cortex, insular cortex, prefrontal cortex, and thalamus = provide an interpretation of the pain and the emotional response to the pain **Ascending pathways** = provide rostral (i.e. superior) transmission to the brain - Pain is perceived via nociceptors located at the free nerve endings of primary afferent neurons - Signal is transmitted via A or C fibers to the dorsal horn of the spinal cord - At dorsal horn, signal synapses with interneurons - Interneurons make up the majority of the dorsal horn neurons and communicate with other neurons in the dorsal horn laminae - Inhibitory interneurons communicate via GABA or glycine - Excitatory interneurons communicate via glutamate - **Projection neurons and interneurons = 2^nd^ order neurons = neurons that originate in the spinal cod** - Anterolateral pathway is composed of the neospinalthalamic tract for A-d fibers/fast pain and the paleospinalthalamic tract for C fibers/slow pain - Neospinothalamic tract = fast pain via A-d fibers - **A-d fibers synapse in lamina I (marginal zone)** and transmit signal to second order/interneurons - Second order neurons/interneurons cross/dessucate to the opposite side of the spinal cord then ascend via neospinalthalamic tract to **thalamus** - At thalamus, second order neurons synapse with third order neurons - NT involved in signal transmission = glutamate - Third order neurons project to the primary somatosensory cortex of the brain - Paleospinothalamic tract = slow pain via C fibers - **C fibers synapse in lamina II and III (substantia gelatinosa**) and transmit signal to second order/interneurons - Second order neurons/interneurons cross then ascend via paleospinalthalamic tract - Paleospinathalamic tract has projections for second order neurons to synapse with the **reticular formation** in the brain stem and projects to the **cingulate gyrus** and the **insular cortex** in the cerebral cortex - NT involved in signal transmission = glutamate instantly and substance P slowly - It is impossible to sleep when in severe pain due to the termination of c fibers in the reticular areas and intralaminar nuclei of the thalamus - Reticular areas and intralaminar nuclei play a role in arousal **Descending pathways** via the periaqueductal grey (i.e. PAG), rostral ventromedial medulla (i.e. RVM) = provide depression of pain or facilitate integration of pain at the dorsal horn - Pain signal arrives at brain from the spinothalamic tract via the ascending pathway - Prefrontal cortex, insula, amygdala, and hypothalamus transmit signal to the PAG - PAG transmits signal to the RVM and Locus ceruleus - RVM transmits signal down spinal cord releasing serotonin to inhibit/excite ascending pain pathways - Locus ceruleus transmits signal down spine releasing NE to inhibit pain in the ascending pain pathways - Descending signal also stimulates interneurons in dorsal horn to release endogenous opioid, enkaphalin - Enkaphalin inhibits release of substance P from presynaptic neuron and inhibit transmission of pain signal from the postsynaptic neuron Stimulation of the PAG, RVM, and locus ceruleus inhibit nociceptive dorsal horn neurons producing analgesic effects Locus cereleus is the main source of the brain's NE - NE inhibits the release of substance P from presynaptic neurons - Locus ceruleus modulates pain via NE and pain perception Discuss the components and mechanism of the Gate Theory - The faster transmission of the Aβ fibers essentially overrides input form the slower Aδ and C fibers. - Rubbing injured skin (A-B fibers) causes sensation that is transmitted faster than A-D or C Define the course and role of: - **Spinothalamic tract** directly projects into thalamus - Most closely associated with pain, temperature, and itch sensation - 85-90% are contralateral - **Spinomedullary and spinobulbar projections** direct project into homeostatic regions in medulla and brainstem - Travel to more primitive parts of brain and allow integration of pain and processes of homeostasis and behavior - **Spinohypothalamic tract** directly projects into the hypothalamus and ventral forebrain Compare and contrast: - Acute pain - Pain ceases when nociceptors no longer detect tissue damage - Lasts days to weeks after injury - Protects injury rom re-injury - Chronic pain - Occurs after injury has healed - Pain receptors continue to fire in the absence of tissue damage - Sensitization forms the neurological basis for the development of chronic pain, but psychological response also plays a role Define and discuss the common features of neuropathic pain - Neuropathic pain is that which persists after injury has healed and characterized by allodynia and hyperalgesia - Common features of neuropathic pain = abnormal myelination/demyelination and axonopathy - After axon injury, an end bulb forms with processes seeking the original neural tube - This results in blocked forward growth causing ectopic firing in the sprouts and the dorsal root ganglia Compare and contrast the features, transmission, and responses to visceral pain - Visceral organs are innervated by vagus/spinal nerves and pelvic parasympathetic nerves - Visceral nerves are A-d, A-b, and C fibers that ascend through contralateral STT or ipsilateral dorsal column - Visceral pain is diffuse and poorly localized with stronger emotional and autonomic reactions - Visceral sensations are transmitted via 2 pathways = visceral pathways and parietal pathways - Visceral pathway via autonomic nerve bundles that lead to referred pain - Parietal pathway allows conduction directly into the spinal cord resulting in more precise localization - Pathways are tied to the embryologic origin of the organ - Parenchyma of the liver and alveoli of lungs are insensitive to pain of any type Compare and contrast Complex Regional Pain Syndrome - Complex regional pain syndrome = CRPS = type of chronic pain that is disproportionate to the initial injury characterized by spontaneous pain, allodynia, hyperalgesia, edema, and movement impairment - Type I = develops after a noxious event but no nerve injury - Type II = develops after nerve injury - Define and describe Brown-Sequard Syndrome - One-sided transection of the spinal cord - Injuries to the spinal cord will cause ipsilateral dysfunction in dorsal column and motor pathways with preservation in ipsilateral anterolateral pathways - Injuries to the spinal cord will cause contralateral dysfunction in anterolateral pathways with preservation in contralateral dorsal and motor pathways - Compare and contrast the pathways and information transmitted by: - Dorsal column-medial lemniscal system - Information = fine touch, 2 point discrimination, vibration, and proprioception - Enter dorsal horn and divide into medial and lateral branches - Enter dorsal horn, ascend, and cross at the level of the medulla - Medulla transmits signal to thalamus - Thalamus transmits signal to somatosensory areas 1 and 2 - Anterolateral system - Information = pain, temperature, crude touch (tickle and itch), and sex sensations - Enter dorsal horn, cross at lamina 2/substantia gelatinosa and ascend to medulla - Medulla transmits signal to thalamus and reticular formation - Thalamus transmits signal to somatosensory areas 1 and 2 - Slower than dorsal column system with less ability to convey rapidly changing or repetitive signals - Motor pathway - Same pathway as dorsal column system -- signal originates at primary motor cortex, crosses at medulla, then descends - Signal originates in motor cortex via upper motor neuron - Upper motor neuron crosses at medulla and signal descends down spinal cord to lower motor neuron and ventral horn of spinal cord - Lower motor neuron exits ventral horn and carries signal to nerve fiber - Compare and contrast: - Warm receptors = c fibers - Cold receptors = A-d fibers - More cold fibers than warm fibers - **Sensory Receptors & Neural Circuits** - List the types of stimuli provoking a response in: - Mechanoreceptors = compression or stretch - Thermoreceptors = temperature - Nociceptors = pain - Electromagnetic receptors = light - Chemoreceptors = taste, smell, PaO2, osmolality - Define the "Labeled Line" Principle = receptor pathways are specific e.g. nociceptor cannot transmit light information - Specificity of nerve fibers only transmitting one modality of sensation - Discuss the relationship between: - Increasing or decreasing ion flow alters the transmembrane potential - Receptor potential must exceed the threshold potential to generate an action potential - The greater the receptor potential exceeds threshold potential, the greater the frequency of action potentials generated - Describe the mechanism responsible for receptor adaptation - All receptors adapt partially or completely to constant stimulation - Adaption mechanisms vary by receptor type - Chemoreceptors and pain receptors never completely adapt - Define "tonic" receptors and list the four types of tonic receptors - Slowly adapting, tonic receptors constantly transmit information to the brain as long as stimulus is present - Tonic receptors = Vestibular apparatus, Pain receptors, Baroreceptors, Chemoreceptors - Rate/movement/phasic receptors adapt rapidly and respond to changes in stimulus strength - These types of receptors are vital in movement and proprioception - Categorize nerve fibers types by - A fibers -- large, myelinated, faster transmission - C fibers -- small, unmyelinated, slower transmission - Define - Spatial summation = increased signal strength spreads to a progressively greater number of nerve fibers - Temporal summation = increased frequency of firing results in a stronger signal in the nerve fiber - Discuss the role of neuronal pools - Neuronal pool = functional group of neurons that play a role in sensory integration - Discharge zone = neurons that are closely associated with the presynaptic fiber (in the middle) and thus receive more NT and have a greater likelihood of depolarizing - Facilitated zone = neurons on the outer edges of the presynaptic fiber that have a lower likelihood of depolarizing - Discuss: - Divergence = one input goes into many neurons - Convergence = multiple inputs and just one output - Sensory information travels to brain via convergence - Reciprocal Inhibition - If we're going to flex our biceps, we need our triceps to relax - Incoming signal generates excitatory in one direction and an inhibitory signal in the other - Reverberating/Oscillatory circuits - Positive feedback loop - Input signal goes to output neuron. Output neuron sends collateral nerve fiber to go back on itself to restimulate itself - Control rhythmic and repetitive actions e.g. breathing and walking - **Somatic Sensation**: - List the three main somatic senses - Mechanoreceptive = tactile (touch, pressure, and vibration) and position - Thermo-receptive = heat and cold - Pain/Nociceptive = tissue damage - List the functions of the Somatosensory Area I - Functions = 2 point discrimination, pressure, weight, shapes, textures - Receives information from the opposite side of the body - Discuss the mechanism responsible for two-point discrimination - The ability to differentiate between two adjacent stimuli referred to as two point discrimination - Strength of stimulus is greatest down the middle - Lateral inhibitions facilitates two-point discrimination because it diminishes sensation at the edge of the field - Increased density of receptor fields is what allows two point discrimination in some places vs others (e.g. can discriminate in fingertips better than back of leg) - Discuss the mechanism and role of proprioceptive sense - 2 types = static position sense and rate of movement sense (kinesthesia/dynamic proprioception)