Exam 2: Lecture 15/16: Pain Mechanisms and Targets Flashcards
what is the definition of pain
an unpleasant sensory and emotional experience associated with or resembling that associated with actual or potential tissue damage
T/F: An inability to communicate does not negate the possibility that a human or nonhuman animal experiences pain
TRUE!!
what is sensory physiology
detection mechanisms for specific stimuli
what are the pathways of sensory physiology
transduction, transmission, modulation, projection, and perception
what is nociception
the sensory nervous systems process of encoding noxious stimuli
what nerve fibers carry pain
A-delta and C fibers
are A-delta myelinated or unmyelinated
myelinated
are c fibers myelinated or unmyelinated
unmyelinated
what pain information specifically do A-delta fibers carry
mechanical and thermal
what pain information specifically do C fibers carry
mechanical, thermal, and chemical
T/F: Nociceptors have a very high threshold compared to touch fibers
TRUE!
where are nociceptors found
in the skin, muscle, and all inner organs
what are the stimuli nociceptors specialized at in detecting
changes in the environment like mechanical forces and chemical changes like inflammatory cytokines, pH, and temp
What type of receptors do nociceptors activate
either a g-protein coupled receptor or a specialized ion channel
what is plasticity
changes at the nervous tissue which amplifies pain signal transmission to the brain
Where are highly plastic neurons found
in the spinal dorsal horn
what are wide dynamic range neurons
neurons that respond to a range of innocuous and noxious mechanical stimuli and exhibit a frequency-dependent, progressive increase in neuronal excitability and ectopic activity
what sensory are wide dynamic range neurons responsible for
touch, itch, pain
what are the 2 biggest players for perception of pain in the brain
amygdala and locus coeruleus
what does the limbic cortex control
behavior
what does the hippocampus control
fear and behavior
what does the septal area control
emotion
what does the hypothalamus control
homeostasis, sympathetic modulation
what does the locus coeruleus control
primary source of NE which is inhibitory
T/F: nociceptors are a protective warning system
true!
Why are stimuli sensed by nociceptors perceived as a warning system to the body
glutamate in increased concentrations activate NMDA receptors to perceive the stimuli as potential tissue damage/painful
What are the 3 things that can happen from prolonged pain
- amplified response to non-painful stimuli
- create and amplify the response to pain stimuli
- create a chronic pain state
what are the 7 pain processes that promote, intensify, and prolong pain
- peripheral sensitization
- central sensitization (activation of NMDA-R)
- activation of silent nociceptors
- disinhibition
- neuroinflammation via glial cell activation
- stress and pain (PTSD)
- collateral sprouting
what is peripheral sensitization
an increased sensitivity of fibers at the site of tissue injury or inflammation which causes a low threshold for pain and greater response to stimuli
WBCs are involved in peripheral sensitization. How?
when there is an injury, WBCs flood the site to clean up the injury but all of the things that WBCs release activates the nociceptors which lowers the threshold
T/F: Macrophages have 3 different types so they are considered plastic
true!
T/F: because macrophages are “plastic” they can increase or decrease pain depending on the surrounding
true!!!!
What cells are involved in pro-inflammatory mediators
T-cells, mast cells, macrophages, and neutrophils
how does central sensitization happen
an increased tissue damage = increased input to CNS = decreased threshold = decreased amount of stimuli to activate
T/F: Central sensitization can not be in a chronic hypersensitized state
False, it can be put into a hypersensitized state due to chronic or prolonged injury
what is the definition of central sensitization
an enhancement neuronal function and nociceptive pathways caused by increased in excitability, synaptic efficacy and reduced inhibition
T/F: Central sensitization is a manifestation of somatosensory plasticity in response to activity, inflammation, and neural injury
true
T/F: central sensitization is linked to acute pain
false, it is linked to development of CHRONIC pain
What are silent nociceptors
receptors that are normally unresponsive to noxious mechanical stimulation but become active to mechanical stimulation during inflammation and tissue injury
where are silent nociceptors located
in the skin and deep tissues with nociceptors
what are the targets of silent nociceptors
TRPV1, TRPV3, TRPV4, TRPV8
What is disinhibition
a temporary loss of normal function/inhibition due to anesthetic medications. The patient is not in full control of their actions
Where do peripheral glial cells live
surround the cell bodies of the neurons and along the axons
what are the main type of cells in neuro-inflammation
schwann cells and satellite cells
If you have acute pain or acute glial activation, what cells respond to the pain intensity
microglia cells are activated
If you have chronic pain or chronic glial activation, what cells respond to the pain intensity
astrocyte activation
T/F: Stress alters the CNS microenvironment and disinhibits the immunoregulatory mechanisms
True!!
what does stress cause when it alters the CNS
it constrains microglial and neuro-inflammatory processes to produce a primed state of activation
what are alarmins
danger signals
what are DAMPs
damage-associated molecular pattern molecules
what is HMBG1
a stress protein and cytokine mediator of inflammation
Do we know a lot about collateral sprouting
we sure dont… it is a topic that is not that studied
what is collateral sprouting for fibers
sprouting of collateral A-beta fibers from sensory axons into superficial dorsal horn laminae
T/F: T and B cells are lymphocytes but have a small job in the activation of nociceptors
false! They are a key component of the adaptive immune system for activating nociceptors
T/F: T and B cells contribute to the inflammatory response and influence the transition from acute to chronic pain
TRUE!! Pain chronification
T/F: T cells attack infected cells but do not increase pain
false, they attack infected cells and increase pain by releasing pro-inflammatory cytokines
T/F: B cells produce antibodies to fight pathogens which causes nociceptor sensitization and altered membrane trafficking
true!!
When does acute pain become chronic
when we do not properly treat the pain when it happens
why does persistent post surgical pain happen
because we are not the best at treating pain when it happens :(
what the definition of pain chronification
a maladaptive form of neuropathic pain involving peripheral and central sensitization, CNS plasticity, and a loss of inhibition
what can pain chronification also be called
transient pain progressing to persistent pain
what is maladaptive pain
pain that doesn’t promote healing and repair
what is the evidence of nociceptive pain state
evidence of noxious insult
what are the symptoms of nociceptive pain state
pain localized to area of stimulus/joint damage
what are the signs of nociceptive pain state
on imaging will see mechanical pathology/altered joint architecture such that normal movements will likely produce excessive forces sufficient to activate nociceptors
what is the evidence of inflammatory pain state
sterile or infectious inflammation
what are the symptoms of inflammatory pain state
redness, warmth, or swelling of infected area
what are the signs of the inflammatory pain state
on imaging will see signs of inflammatory changes
will also detect pathogens/response to abx
what is the evidence of neuropathic pain state
evidence of sensory nerve damage
what are the symptoms of neuropathic pain state
decreased pinprick pr vibration sense, straight leg raise, and mechanical and cold allodynia
what is the evidence of dysfunctional/nociplastic pain state
pain the the absence of detectable pathology
what are the signs/symptoms of dysfunctional/nociplastic pain state
no identifiable noxious stimulus, inflammation, or neural damage, evidence of increased amplification or reduced inhibition with abnormal excitability and connectivity
what is hyperesthesia
increased sensitivity to stimulation
what is hyperalgesia
increased pain from a stimulus that normally produces pain
what is hyperpathia
an abnormal reaction to repetitive painful stimulus
what is allodynia
pain due to a stimulus that does NOT normally produce pain
what is adaptive pain
pain that produces behavior that promotes healing and recovery
what is maladaptive pain
pain that is out of proportion to tissue damage or which persists after tissue healing
T/F: Maladaptive pain promotes and supports healing and repair
FALSE it does not
what is pain chronification
the process of transient pain progressing into persisten pain
what are the classifications of pain
location, severity, and mechanism
how can you describe pain location
is it somatic or visceral
how can you describe severity of pain
mild, moderate, or severe
what are the different mechanisms of pain
inflammatory, neuropathic, and idiopathic
what are the 6 ways we can assess pain
- visual analogue scales (behavior)
- simple categorical descriptive scales
- numerical rating scales
- time/activity analysis
- compositie pain scales
- grimace scale (the WORST WAY in muirs opinion)
what are the routes of pain therapy
- pharmacologic
- Physical therapy
- electrical
- complimentary
- herbal/nutraceutical
- environmental
what are the goals of multimodal analgesia
additive or synergistic analgesic effects
what is synergism
the interaction or cooperation of two or more substances to produce a combined effect greater than the sum of their separate effects
list some of the routes of drug administration
- oral (PO)
- IV
- IM
- SQ
- topical (transdermal, TD)
- intra-articular (IART)
what are the names of local anesthetics we use
lidocaine, mepivacaine, bupivacaine, ropivacaine
what is this a picture of
lidocaine patch
what NSAIDs are salicylic acid
aspirin
what NSAIDs are para-aminophenol
acetominiphen
what NSAIDs are fenamic acids
flunixin megulamine
what NSAIDs are pyrazolones
dipyrone
what NSAIDs are acetic acids
ketorolac
what NSAIDs are proprionic acids
carprofen, ketoprofen, naprozen
what NSAIDs are oxicams
piroxicam and meloxicam
what NSAIDs are coxibs
deracoxib, firocoxib, robenacoxib
What type of drug is galliprant
a non-steriodal, non-cyclooxygenase inhibitor of PGE2 EP4 receptor antagonist
what is galliprant used for
pain and inflammation
how do opioids cause sedation
inhibition of adenylyl cyclase, closure of voltage-gated Ca channels, and opening of K channels and membrane hyperpolarization
what is opioid induced neurotoxicity
euphoria or excitement
what drugs are opioid agonists
morphine, hydromorphone, methadone, and fentanyl
what drugs are partial opioid agonists
butorphanol, buprenorphine, nalbuphine
what drugs are opioid antagonists
naloxone, naltrexone
what drugs are alpha-2 agonists
xylazine, clonidine, detomidine, romifidine, medetomidine, dexmedtomidine, zenalpha
what are alpha-2 antagonists
yohimbine, tolazoline, atipamazole
what is zenalpha made up of
medetomidine and vatinoxan
how do ketamine and magnesium work
block NDMA receptors to decrease perception
is there any evidence that homeopathic meds work? What are 2 examples
traumeel and cannabis….no evidence
what are some nutraceuticals used for osteoarthritis (supplements)
hyaluronic acid, ascorbic acid, chondroitin sulfate, collagen hydrolysate, vitamin D, vitamin E
