Lecture 12 Flashcards
What is pain?
Pain:
Feeling or perception
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Complex sensory modality
Nocicpetion:
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
Nociceptors are free nerve cell endings that initiate the sensation of pain
Slide 1 lecture 12
What are the 3 major classes of nociceptors in the skin?
- Aδ mechanosensitive nociceptors -> mechanical
Myelinated axons! - Aδ thermal nociceptors -> (>45oC or <5oC)
Myelinated axons! - C fiber polymodal nociceptors -> mechanical, chemical, thermal
Unmyelinated axons!
The 3 often work together contributing to the perception of pain
Slides 2-3 lecture 12
What are the 2 categories of pain perception?
Which axons mediate each type?
- First pain (fast, sharp)
Mediated by fast Aδ axons - Second pain (delayed, diffuse, longer-lasting, dull)
Mediated by slow C fibers
Slide 4 lecture 12
Explain the transduction of nociceptive signals.
What are TRPV1 channels?
Noxious stimuli depolarize free nociceptor endings and generate action potentials that are propagated centrally
Membrane of the nociceptor contains unique receptors that subserve the transduction of the thermal, mechanical or chemical energy of noxious stimuli into a depolarizing electrical potential
TRPV1 expresses selectively by nociceptive neurons and transduce sensation of lingual heat, mediated pain action of capsaicin
Variety of TRP channels underlie perception of wide range of temps
Slide 5-6 lecture 12
What is voltage gated sodium channel NaV1.7?
Voltage gated sodium channel selectively expressed in sensory neurons
Important for transduction of noxious stimuli
Slide 7 lecture 12
Are there pain fibers in the dorsal root ganglia?
Yes, pain fibers have cell bodies in the dorsal root ganglia
Slide 8 lecture 12
Where do nociceptive afferent fibers terminate?
Nociceptive afferent fibers terminate on projection neurons in the dorsal horn
Slide 9 lecture 13 diagram
What is referred pain?
Condition in which pain from injury to a visceral structure is displaced to other areas of the body surface
Convergence of somatic and visceral nociceptive input to the substantia gelatinosa -> a single projection neuron receives input from both regions
Slide 10 lecture 12
What is the gate control theory of pain?
Local interactions between mechanoreceptive affferents and neural circuits within dorsal horn can modulate the transmission of nociceptive information to higher centres
These interactions are thought to explain the ability to reduce sharp pain by activating low-threshold mechanoreceptors
Slide 11 lecture 12
What are the 2 major classes of neurotransmitters released by nociceptive neurons that activate neurons in the dorsal horn of the spinal cord?
Glutamate is the primary neurotransmitter
Neuropeptides released as cotransmitters (substance P, calcitonin gene-related peptide, etc)
Substance P is concentrated in the terminals of primary sensory neurons in the superficial dorsal horn, it’s receptor is NK1
Slide 12 lecture 12
How are transmitters stored?
Transmitters stored in afferent synaptic terminals
Glutamate is stored in small, electron-lucent vesicles, whereas peptides are sequestered in large, dense-core vesicles at the central terminals of nociceptive sensory neurons
Separate storage sites permit 2 classes of transmitters to be released under different physiological conditions
Neuropeptides released with intense stimulation
Slide 13 lecture 12
What is sensitization?
What is hyperalgesia?
What is allodynia?
Sensitization- upon repeated application of noxious stimuli, nearby nociceptors that were previously unresponsive to stimuli now become responsive
Hyperalgesia- stimuli in area of an injury and the surrounding region that would ordinarily be perceived as slightly painful are perceived as significantly more so
Allodynia- the induction of pain by what is normally an innocuous stimulus
Slide 14 lecture 12
What is peripheral sensitization?
Results from interaction of nociceptors with the substances released when tissue is damaged
Plenty things (extracellular protons, bradykinin, histamine, serotonin, nucleotides, etc) can interact with receptors or ion channels of nociceptive fibers, augmenting their response by decreasing the threshold for activation
Example slide 16
Comparison slide 17
Slides 14-17 lecture 12
What are analgesics?
Compounds that reduce pain intensity
Nonsteriodal anti-inflammatory drugs (NSAIDs) that include aspirin, ibuprofen act by inhibiting cyclooxygenase (COX), enzyme important in the biosynthesis of prostaglandins
Slide 18 lecture 12
What is neurogenic inflammation?
Tissue inflammation that results from release of the neuropeptides substance P and CGRP from peripheral terminals of C fibers
Cardinal signs of inflammation are heat (calor), redness (rubor), and swelling (tumor)
Heat and redness result from dilation of peripheral blood vessels
Swelling results from plasma extravasation (proteins cells and fluids are able to eoentrare post capillaries vessels)
Slide 19-21 lecture 12
