Pain Flashcards
What is pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage
What are the two aspects pain can be divided into
Sensory-discriminative aspects: the location, intensity, and quality of the noxious stimulation.
Affective-motivational aspects: the unpleasant feeling, the fear and anxiety, and the autonomic activation that accompany exposure to a noxious stimulation
How can hypnosis affect pain?
It might alleviate pain by decreasing the activity of brain areas involved in the experience of suffering
What is pain without unpleasantness called?
Asymbolia
What is asymbolia?
Patients with lesions in the anterior cingulate or insular cortex who perceive noxious stimuli as painful and can distinguish sharp from dull and identify the location and intensity but fail to display the appropriate emotional response
They perceive the noxious stimuli but fail to display the emotional response
what is the false alarm theory of Ramachandran
When the insular cortex is damaged, patients giggle in response to pain, presumably because they can still sense the pain (‘danger’) but the pain is no longer aversive (‘false alarm’), thereby fulfilling the two key requirements for laughter.
what is social pain
The unpleasant experience that is associated with actual or potential damage to one’s sense of social connection or social value
what region of the brain mediates the emotional distress of pain
anterior cingulate cortex
Does social rejection cause similar reactions as physical pain?
yes, social rejection activates the anterior cingulate cortex which mediates emotional distress of pain from physical damage
What is nociception? What are nociceptors? Free nerve endings?
Nociception: the sensory neural processes of encoding and processing noxious stimuli, depends on specifically dedicated receptors and pathways distinct from the sensory processing of ordinary mechanical stimulation
Nociceptor: The unspecialized free nerve cell endings that respond to stimuli that produce tissue damage and initiate the sensation of pain
Free nerve ending: an axon that terminates in the skin without any specialized cell associated with it and that detects pain and/or changes in temperature
What is a receptor cell
A specialized cell that responds to a particular energy or substance in the internal or external environment and converts energy into a change in the electrical potential across its membrane
What are labeled lines
the concept that each nerve input to the brain reports only a particular type of information
What is sensory transduction
The process in which a receptor cell converts the energy in a stimulus into a change in electrical potential across its membran
What is a receptor potential
Also called generator potential. A local change in the resting potential of a receptor cell that mediates between the impact of stimuli and the initiation of action potentials.
Describe the receptor type, axon type, diameter, and conduction speed of proprioception
Receptor type: Muscle spindle
Axon type: A alpha
Diameter: 13-20
Conduction speed: 80-120
Describe the receptor type, axon type, diameter, and conduction speed of touch
Receptor type: Pacinian corpuscles, Ruffini’s endings, Merkel’s discs, Meissner’s corpuscles
Axon type: A beta
Diameter: 6-12
Conduction speed: 35-75
Describe the receptor type, axon type, diameter, and conduction speed of pain and temperature
Receptor type: Free nerve endings
Axon type: A delta
Diameter: 1-5
Conduction speed: 5-30
Describe the receptor type, axon type, diameter, and conduction speed of temperature, pain, and itch
Receptor type: Free nerve endings
Axon type: C
Diameter: 0.2-1.5
Conduction speed: less than 1
Which primary afferent fibres carry first pain? Which one carries second pain?
Thinly myelinated fibres carry first pain (A delta)
Unmyelinated fibres carry second pain (C fiber)
Describe the pathway of transduction of nociceptive signals
Noxious stimuli are transduced into electrical activity at peripheral terminals of nociceptors by specific receptors. This activity is conducted to the spinal cord and after transmission to the cortex where the sensation of pain is experienced
Describe the TRP channel activation pathway
Bradykinin (BK) binds to G protein-coupled receptors on the surface of primary afferent neurons to activate phospholipase C (PLC), leading to the hydrolysis of membrane phosphatidylinositol bisphosphate (PIP2), the production of inositol 1,4,5-trisphosphate (IP3), and the release of Ca2+ from intracellular stores. Hydrolysis also results in the activation of protein kinase C (PKC) which regulates TRP channel activity. The TRPV1 channel is sensitized, leading to channel opening and Ca2+ influx.
Order the following channels from lowest temperature to highest
TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, TRPM8
TRPA1:
TRPM8:
TRPV4:
TRPV3:
TRPV1:
TRPV2:
What activates TRPV1
Capsaicin
What temperatures do TRPM8, TRPV1, and TRPM3 detect? Which fibres do they transmit over?
TRPM8: temperatures below normal body temperature, C fibres
TRPV1(Capsaicin): Moderate heat, C fibres
TRPM3: High temperatures, myelinated A-delta fibres
Transient receptor potential vanilloid type 1 (TRPV1) Also called vanilloid receptor 1. A receptor that binds capsaicin to transmit the burning sensation from chili peppers and normally detects sudden increases in temperature.
Transient receptor potential type M3 (TRPM3) A receptor, found in some free nerve endings, that opens its channel in response to rising temperatures.
TRPM8 Also called cool-menthol receptor 1 (CMR1). A sensory receptor, found in some free nerve endings, that opens an ion channel in response to a mild temperature drop or exposure to menthol.
What is range fractionation?
A hypothesis of stimulus intensity perception stating that a wide range of intensity values can be encoded by a group of cells, each of which is a specialist for a particular range of stimulus intensities.
What is hyperalgesia?
Increased sensitivity, resulting from sensitization of nociceptors
Describe the pathway of peripheral sensitization
Tissue injury and inflammation lead to the release of numerous chemicals from non-neuronal and neuronal cells such as mast cells and macrophages. These cells release mediators such as protons, purines, and cytokines. These may directly or indirectly alter sensitivity of peripheral nociceptors.
Mast cell degranulation
What is allodynia, hyperalgesia, and hypoalgesia
Allodynia: Pain caused by a normally non-painful stimulus
Hyperalgesia: A heightened experience of pain caused by a noxious stimulus
Hypoalgesia: A decreased perception of pain caused by a noxious stimulus
Describe the efferent actions of nociceptors
A noxious stimulus leads to action potentials in nociceptive fibers that propagate not only to the central nervous system but also antidromically into peripheral branches. These antidromic action potentials lead to the release of neuropeptides such as substance P, calcitonin gene–related peptide (CGRP), and neurokinin A (NKA). These substances can stimulate epidermal cells (1) and immune cells (2) or lead to vasodilatation (3), plasma extravasation (4), and smooth muscle contraction (5)
What are CGRP
Potent vasodilators
Describe neurogenic inflammation
Injury or tissue damage releases bradykinin and prostaglandins, which activate or sensitize nociceptors. Activation of nociceptors leads to the release of substance P and CGRP (calcitonin gene–related peptide). Substance P acts on mast cells in the vicinity of sensory endings to evoke degranulation and the release of histamine, which directly excites nociceptors. Substance P produces plasma extravasation, and CGRP produces dilation of peripheral blood vessels; the resultant edema causes additional liberation of bradykinin. These mechanisms also occur in healthy tissue, where they cause secondary or spreading hyperalgesia.
Which channels are particularly important in the transformation of generator potentials to action potentials?
NaV 1.7 in the pacemaker zone
Why do grasshopper mice not show pain in response to bark scorpion venom?
The bark scorpion toxin activates Nav1.7 channels in grasshopper mice and lab mice. But in grasshopper mice, the toxin potently inhibits the Nav1.8 channel in the same sensory neurons, tipping the balance to inhibit action potential firing in nociceptors. This evolutionary adaptation allows grasshopper mice to feed on bark scorpions with impunity. In contrast, the lab mouse Nav1.8 channel is not blocked by the toxin and the scorpion sting excites nociceptors, causing intense pain
describe the organization of the dorsal horn. A-delta, A-Beta, and C fiber?
Neurons in lamina I of the dorsal horn receive direct input from myelinated (Aδ) nociceptive fibres and both direct and indirect input from unmyelinated (C) nociceptive fibres via interneurons in lamina II. Lamina V neurons receive low-threshold input from large-diameter myelinated fibres (Aβ) of mechanoreceptors as well as inputs from nociceptive afferent fibres (Aδ and C fibers). Lamina V neurons send dendrites to lamina IV, where they are contacted by the terminals of Aβ primary afferents. Dendrites in lamina III arising from cells in lamina V are contacted by the axon terminals of lamina II interneurons. Aα fibres innervate motor neurons and interneurons in the ventral spinal cord (not shown).
What is referred pain? How does it happen? Describe the pain in myocardial infarction and angina?
Signals from nociceptors in the viscera that can be felt elsewhere in the body.
Convergence of visceral and somatic afferent fibers may account for referred pain. Nociceptive afferent fibers from the viscera and fibers from specific areas of the skin converge on the same projection neurons in the dorsal horn. The brain has no way of knowing the actual site of the noxious stimulus and mistakenly associates a signal from a visceral organ with an area of skin
Myocardial infarction and angina can be experienced as deep referred pain in the chest and left arm. The source of the pain can be readily predicted from the site of referred pain
What are the two classes of synaptic vesicles and which neurotransmitters to they transport?
small electron-lucent vesicles contain glutamate
Large dense-cored vesicles hold neuropeptides.
how does pain reach the brain?
Through the anterolateral system aka spinothalamic system
what is the anterolateral system
Also called spinothalamic system. A somatosensory system that carries most of the pain and temperature information from the body to the brain
describe the anterolateral pathway
Primary afferent axons terminate in dorsal horn –> secondary axons cross the midline –> ascend contralateral anterolateral column to thalamus
Describe the doral column pathway
Primary afferent axons enter spinal cord –> ascend ipsilateral dorsal columns –> synapse in medulla –> secondary axons cross the midline –> ascend to contralateral thalamus.
Describe Brown-Sequard syndrome
Hemicord lesion
What will a lesion restricted to the left half of the spinal cord result in?
Results in dissociated sensory loss and mechanosensory deficits in the left half of the body, with pain and temperature deficits on the right
What is naloxone
A potent antagonist of opiates that is often administered to people who have taken drug overdoses. It blocks receptors for endogenous opioids
What is analgesia
Absence of or reduction in pain
What are opiates
A class of compounds that exert an effect like that of opium, including reduced pain sensitivity
What are endogenous opioids
A class of peptides produced in various regions of the brain that bind to opioid receptors and act like opiates.
What are endorphins, enkephalins, and dynorphins?
three kinds of endogenous opioids, substances that reduce pain perception
What are opioid receptors
A receptor that responds to endogenous and/or exogenous opioids
What is periaqueductal gray
The neuronal body–rich region of the midbrain surrounds the cerebral aqueduct that connects the third and fourth ventricles. It is involved in pain perception
Describe the regulation of nociceptive signals at dorsal horn synapses. How do opiates affect it?
- Activation of a nociceptor leads to the release of glutamate and neuropeptides from the primary sensory neuron, producing an excitatory postsynaptic potential in the projection neuron.
- Opiates decrease the duration of the postsynaptic potential, probably by reducing Ca2+ influx and thus decreasing the release of transmitter from the primary sensory terminals. In addition, opiates hyperpolarize the dorsal horn neurons by activating a K+ conductance and thus decrease the amplitude of the postsynaptic potential in the dorsal horn neuron.
What are electroencephalograms?
Offers a window into brain function
Describe how the very small electrical fields are generated by synaptic currents in pyramidal cells
the active synapse is on the upper part of the dendrite. When the afferent axon fires, the presynaptic terminal releases glutamate, which opens cation channels. Positive current flows into the dendrite, leaving a slight negativity in the extracellular fluid. Current spreads down the dendrite and escapes from its deeper parts, leaving the fluid slightly positive at those sites.
How are large EEG signals generated?
If the inputs fire within a narrow time window, the pyramidal cell responses are synchronized, resulting in a large EEG
Describe delta rhythms
<4 Hz large in amplitude, a hallmark of deep sleep
