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what are nociceptors
receptors that terminate free nerve endings and respond to noxious stimulus and generate nerve impulses that the brain perceive as pain signals
what do nociceptors respond to
noxious stimulus
what do nociceptors generate
nerve impulses that the brain perceive as pain signals
what stimuli do nociceptors respond to
thermal-mechanical and chemical
what are the 4 neural steps in the processing of pain signals
transduction, transmission, modulation, and perception
transduction
noxious stimuli are converted to electrical signals in sensory nerve endings
transmission
neural events which relay the information from the periphery to the cortex
modulation
the nervous system can selectively inhibit the transmission of pain signals
perception
subjective interpretation by the cortex of the noxious stimulus
what are the 2 components of perception
sensory component and affective component
what is the therapeutic goal for pain
eliminate abnormal pain without interfering with normal - protective pain
nociceptive pain processing
Noxious stimuli (Heat, cold, intense mechanical force, chemical irritants) -> nociceptor -> spinal cord -> adaptive, high-threshold pain early warning system (protective)
what is the response to nociceptive pain
autonomic response withdrawal reflex
inflammatory pain processing
peripheral inflammation & tissue damage -> spinal cord -> adaptive, low-threshold pain; tenderness promotes reapari (protection)
what are the 4 potential
macrophage, mast cell, neutrophil, and Granulocyte
name the 2 paths for pathological pain processing
neuropathic pain and dysfunctional pain
neuropathic pain pathway
neural lesion, positive and negative symptoms -> peripheral nerve damage -> abnormal central spinal processing -> stroke OR -> maladaptive , low-threshold pain disease state of nervous system
dysfunctional pain pathway
no neural lesion, no inflammation, positive symptoms -> normal peripheral tissue and nerves -> abnormal central spinal processing -> maladaptive, low-threshold pain disease state of nervous system
what kind types of pain and their central processing goes with spontaneous pain & pain hypersensitivity
inflammatory and pathological pain
what is familial erythromelalgia
autosomal-dominant condition with painful spontaneous burning pain of feet and/or hands, increased skin temp
what mutation causes Erythema
mutations in SCN9A - encoding a sodium channel alpha subunit
characteristics of Aß-fibers
Myelinated Non-nociceptive; Vary Fast conduction; convey light touch and vibration; may become nociceptive after nerve injury
what do Aß-fibers convey
light touch and vibration
what can afferent nerve fiber can become nociceptive after injury
Aß-fibers
characteristics of Aδ-fibers
Myelinated Nociceptors; fast conduction; convey fast "picking" pain, punctate stimuli, cold, thermal
what do Aδ-fibers convey
fast "picking" pain, punctate stimuli, cold, thermal
Characteristics of Nociceptive C-fibers
UNmyelinated nociceptors; slow conduction; convey slow "burning" and "aching" pain - polymodal (high-threshold mechanical, thermal, cold)
what afferent nerve fibers are nociceptors
Aδ-fibers and C-fibers
what do Nociceptive C-fibers convey
slow "burning" and "aching" pain - polymodal (high-threshold mechanical, thermal, cold)
TRP channels (transient receptor potential)
respond to a number of strong stimuli
what does TRPM8 stimulated by
cool temperature and menthol
what happens when TRPM8 is stimulated by menthol
since TRPM8 responds to both cool temp and menthol - response is same as cold temp
what does TRPV1 stimulated by
capsaicin and noxious heat
what happens when TRPV1 is stimulated by capsaicin
a noxious heat is felt
what kind of surface receptors can nociceptors also express? and what does it lead to
GPCRs and Try receptors - sensitization of the nerve endings
what is allodynia
perception of pain from a normally non-painful stimulus
what is hyperalgesia
exaggerated perception of pain from a normally painful stimulus
where is the Dorsal Root Ganglion (DRG)
spinal cord
ascending pain system
transmits information from nerve endings to the brain (peripheral -> CNS)
Descending pain system
allows the brain to modulate incoming information by sending projections down to the spinal cord (CNS -> peripheral)
what are opioids
Highly effective analgesics
what do presynaptic opioids do
block Ca++ influx; open K+ channels - K+ efflux (leave cell making more negative); decrease excitatory neurotransmitter release
what do postsynaptic opioids do
open K+ channels; hyper polarize 2 degree - order neuron; inhibit action potential generation
what does Acetaminophen do
inhibits COX, But different from NSAIDss
side effects of Acetaminophen overdose
kidney and liver failure
what do NSAIDs do
inhibit COX1 and COX2
what does inhibiting COX enzymes do
stop the process of converting Archidonic acid to Prostaglandins
some notable NSAIDs
aspirin, diclofenac, ibuprofen, naproxen, ketorolac, celecoxib, ketoprofen, and indomethacin
side effects of NSAIDs over usage
nausea, vomiting, diarrhea/constipation, rash, ULCERS, kidney failure, liver failure, and prolonged bleeding
what can aspirin in children and teenagers with chickenpox or influenza do
develop Reye's syndrome - acute pressure in the brain and massive accumulations of fat on the liver
What are the 3 types of opioid receptors
Mu, Delta, and Kappa
Morphine
Mu opined agonist (codeine is less potent morphine)
fentanyl
100 times more potent than morphine
methadone
orally available, long half life
buprenorphine
partial Mu opioid agonist
Pentazocine
Kappa and Mu opioid agonist
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