Pain Physiology Flashcards
What is pain?
unpleasant sensory or emotional experience associated with actual, perceived, or potential tissue damage
- very subjective!
What is nociception? What are the 5 steps?
processing of pain from outside to inside by a system of neurons integrated with autonomic, endocrine, and musculoskeletal systems
- transduction
- transmission
- modulation
- projection
- perception
What are 4 causes of mild pain?
- superficial skin laceratino
- SQ mass removal
- lymph node aspiration
- routine dentals
What are 3 causes of moderate pain?
- OVH and castrations
- dental extractions and vital procedures
- pancreatitis, myocardial disease
What are 3 causes of severe pain?
- fracture and fixation
- cavitary pain
- abdominal trauma or exploratory
What are 4 causes of excruciating pain?
- multiple fracture trauma
- pleuritis
- head trauma
- abdominal organ capsular expansion
What are 4 potential sites for the generation of signals relevant for pain formation?
- transduction molecules at nerve injury site
- ectopic discharge from intact nerves distal to injury
- increase in spontaneous activity of dorsal ganglion
- ongoing dorsal horn inputs from sensitized nociceptors in the spinal cord
What are the 7 events following injury to peripheral tissues?
- acute injury provokes a barrage of impulses - seconds
- cut end of proximal fibers restract and swell - minutes
- distal segment degenerates and abnormally discharges - hours
- nucleus degenerates - days
- myelin and axon degenerate - week
- sheath provides conduit for regenerating neuron, aiming to target tissue - scar formation
- target tissue reached and growth stops or neuroma forms
What takes part in nociception transduction?
dendritic nerve terminals of sensory fibers —> A delta and C fibers
Where does peripheral sensitization occur? What does it result in?
site of inflammation and nearby tissues (due to inflammatory soup)
release of substances from damaged (affected) cells = further degranulation and local vasodilation
What is nociception transmission? What 2 parts of the spinal cord take part?
channeling of the action potential along the A delta and C nerve fibers
- dorsal root ganglia - somas of C fiber afferents
- dorsal root - afferent fibers encased in fascial covering
Classification of nerves:
What is nociception modulation? Where does it occur?
initial central amplification or suppression of a signal from the periphery
dorsal most grey matter —> dorsal horn
What must be balanced within dorsal horn cells for operation?
INPUT - neural sensory sympathetic motor neurons
OUTPUT - neural emotional autonomic CNS
What are the 4 states of dorsal horn pain? Which are considered normal? Pathologic?
- normal input, normal output
- normal input, suppressed output
- normal input, enhanced output
- subnormal input, grossly enhanced output - end stage of chronic pain, true pathologic pain
- modes 1 and 2
- modes 3 and 4
What is occurring in the normal function modes of dorsal horn cells?
MODE 1 - depolarization of peripheral neurons causes normal excitatory amino acids release with output proportional to stimulus received (initial response)
MODE 2 - output is inhibited by A beta fibers slowing C fiber activity and descending pathways from the limbic system slowing down transmission (how the body copes and drugs take care of pain)
What 5 things occur during Mode 3 in dorsal horn cells?
normal input, enhanced output due to consistent activity
- substance P dumping
- phosphorylation
- voltage-gated channel opening
- calcium influx
- excessive gene induction and expression
What 3 things occur during Mode 4 in dorsal horn cells?
subnormal input, grossly enhanced output
- sprouting processes
- activation of glial cells
- cell death of overexcited inhibitory neurons
What 4 things can alter normal dorsal horn cell function?
- insults that persist or aren’t suppressed well enough (poor pain control)
- massive pain input
- tissue functionally change due to central sensitization
- tissues structurally change (plasticity)
Where does central sensitization occur? What happens?
dorsal horn and ascending tracts
repetitive sensory input causes a release of glutamate from primary afferents, especially in dorsal root ganglia, NMDA receptor Mg stopper dislodgement, and Ca influx
What cascades are activated during central sensitization?
- nitric oxide production
- regulation of gene expression
What role do glial cells take in central sensitization? What additional role do they have?
generation and maintenance of pathologic pain due to activation in response to nerve trauma or proinflammatory mediators (IL-1 beta, TNF alpha, and IL-6)
compromise opioid efficacy for management of chronic pain
What is plasticity?
functional rewiring of pain circuitry where the pain signal changes over time due to differences in nature and intensity of pain
How does plasticity affect the dorsal horn?
decreases in tonic and inhibitory tone (excitability) due to upregulation of cFos and cjun
What are the 4 end results of plasticity and sensitization of the dorsal horn?
- dorsal horn cell exhaustion and death
- axon terminal degeneration
- new terminal appearance
- structural contact between DRG and DH cells monified
What affects the differences in acute and chronic pain?
time interval and healing evidence
What is the difference between acute and chronic pain?
ACUTE = signals actual or potential tissue damage and stops long before healing is complete due to normal dorsal horn cell function
CHRONIC = markedly disassociated from tissue damage and persists long beyond normal time of healing
What is chronic pain?
result of the body’s inability to restore its physiological functions to normal or pre-pain homeostasis levels
What neural pathways occur during acute and chronic pain?
ACUTE = nociception where pain is sensed
CHRONIC - body’s response to sensitization and plasticity where it cannot stop hurting due to altered dorsal horn interneuron cell structure and function
What is nociception projection?
process whereby nociceptive info is conveyed to the brain by bundles of white nerve fibers originating in the dorsal horns
- second order neurons
In what 3 regions of the brain does pain perception occur?
- cortex - integration and ultimate processing
- thalamus - link between incoming signals and cortex
- limbic system - couples input with emotion, autonomic activity, and behavior (motor activity)
What are some examples of acute and chronic pain?
ACUTE - myocardial pain, traumatic MS pain, headache
CHRONIC - oncologic pain, osteoarthritis, neurologic pain, nerve injury (ongoing, difficult to treat!)
What’s the difference between the pathophysiology of nociceptive and neuropathic pain?
NOCICEPTIVE = continued injury to structures
NEUROPATHIC = abnormal changes in PNS/CNS without continued injury
What are 2 types of nociceptive pain?
- somatic - aching, stabbing, throbbing, well-localized (slough from chemo extravasation, bone metastasis, dermal or muscular injury)
- visceral - cramping or aching due to viscus movement, but can be sharp with organ capsule stretching, waxing and waning, usually diffuse (ischemia of visceral muscle)
What are 3 types of neuropathic pain?
- nerve compression or infiltration - burning, pricking, electric, shocking located in areas of compressed nerves, nerve roots, or plexus (tumor invasion into nerve)
- deafferentation injury - prolonged nerve compression or infiltration damages nerve with loss of sensation and ectopic foci (phantom limb pain)
- sympathetically mediated cancer pain - CNS pathology due to sustained efferent activity
What are the 3 possible causes of sympathetically mediated cancer pain? How does it affect the patient?
- nociceptive visceral afferent link sympathetic fibers
- damaged nociceptors
- sympathetic nociceptor ephapses
- burning and swelling
- vasomotor instability
- abnormal heat and sweating
- trophic changes
How is pain categorized?
PQRST
- Provocation
- Quality or mechanism
- Radiation or Region
- Severity or Score
- Temporal (duration)
What are 6 immediate consequences of untreated pain?
- heightened metabolic rate
- increased sympathetic tone
- increased cardiac workload
- diminished pulmonary function
- decreased GI blood flow
- increased platelet aggregation
What are 6 long-term consequences of untreated pain?
- increased incidence of arrhythmias
- GI stress ulceration/translocation
- increased venous stasis = thromboembolism
- poor wound healing
- immunosuppression
- chronic pain states
How should a patient’s behavior be taken into consideration when assessing pain?
- if they are not displaying typical pain behavior, this doesn’t mean they aren’t painful
- no behavior in and of itself is pathognomonic for pain
What 6 things can affect behavior displayed by patients?
- species
- breed
- age
- personality
- environment
- duration and severity of pain
How often should pain be assessed based on severity?
ACUTE = more often
How are patients generally monitored for pain? What is the gold standard treatment?
ANTHROPOMORPHIZE —> if they appear painful, they probably are!
give an analgesic
How does acute and chronic pain assessment compare?
ACUTE - physiologic indicators, classic overt behavioral indicators
CHRONIC - few physiologic indicators, subtle behavior, QoL scores
What objective and subjective tools are available for diagnosing acute pain?
OBJECTIVE - objective scores, physiologic indicators
SUBJECTIVE - visual analog scale, numerical rating system, simple descriptive scale (pain scales)
What are 4 problems with simple pain score systems?
- uni-dimensional
- not great at detecting subtle or gradual signs of pain
- big picture is seen, but details that provide continual pain are missed
- variability in pain scoring among veterinary staff looking at the same patient can be high
What are the 3 objective scoring systems available?
- Glasgow composite pain scale
- Melbourne pain scale
- Botucatu feline pain scale
What are some disappointing physiologic parameters and serum biochemistry variables in pain diagnosis?
PHYSIOLOGIC - HR, pulse rate, RR, temperature, bP
BIOCHEM - cortisol, endorphins, neuropeptide substance P
What are 6 behavioral characteristics of acute pain?
- abnormal posture - haunched, prayer position, not able to rest
- abnormal gait - stiff, no to partial weight bearing, slight to obvious limp
- abnormal movement - thrashing, restless, no movement when not sleeping
- vocalization - screaming, whining, crying
- cocentration on painful area
- hyperesthesia, hyperalgesia, allodynia
What are 5 physiological signs indicative of acute pain?
- tachypnea or panting
- tachycardia
- dilated pupils
- hypertension
- sweating
What are some indications of acute pain in dogs?
- hunched or abnormal body position
- glazed facial expression
- attention-seeking and whining
- licking/hiding painful area
- constant movement
- inappetence, lameness, plegia
- nervous facial expression
- increased RR and abnormal character
- increased HR
- aggression, altered interaction
What are 8 key feline acute pain signs?
- vocalization
- reclusiveness
- decreased movement
- inappetence
- lack of grooming
- hunched posture
- tachypnea
- decreased eyelid aperture
What are some equine acute pain indications?
- restlessness
- head-lowering, teeth-grinding, head-turning
- flaring nostrils
- sweating
- rigid posture
- kicking at abdomen
- reluctance to be handled
- rolling
- tachycardia, tachypnea
- skin twitching
- lameness, pawing, looking at body parts
What are some ruminant acute pain indications? Is vocalization common?
- hunching posture
- lying down
- head-pressing, teeth-grinding, foot-stamping, tail-flicking
- lack of cuddling, isolation from herd
- falling and rolling when in severe pain
- tachypnea, expiratory grunting, tachycardia
NO - except in goats
How does pain compare to emergence delirium?
PAIN - non-consolable, consistent signs, escalating pain, acute pain
ED - often consolable with touch, voice, and food, waxes and wanes, can be accompanied by neuro changes (sight, position)
What are the 3 steps in differentiating pain from emergence delirium?
- opioid - Fentanyl
- sedative - Aceproazine, Medetomidine, Dexmedetomidine
- reversal agent/sedative - Butorphanol
What are some common sources of chronic pain in dogs and cats?
- trauma, injury
- osteoarthritis
- cruciate ligament injury
- patellar luxation
- hip laxity
- pancreatitis
- pleuritis
- cystitis
- IBD
- stomatitis
- glaucoma
- conjunctivitis
Modulation of the pain signal occurs in the:
a. Dorsal horn lamina cells
b. Nociceptors
c. Ventral horn cells
d.Motor nerves
e. thalamus
A
There is a distinct test for whether pain is occurring in a domesticated veterinary patient and it is known as:
a. Endorphin levels
b. CPL=canine pain litmus test
c. Norepinephrine levels
d. No such test exists currently
e. The pain gauge
D
Which of the following nerve fibers transmit a painful signal at 20-30m/sec and are myelinated?
a. Beta fibers
b. A alpha fibers
c. A delta fibers
d. A beta fibers
c. B fibers
C
All of the following classes of analgesics work to reduce transduction EXCEPT:
a. Opioids
b. Local anesthetics
c. Alpha agonist agents
d. Steroids
e.Nonsteroidal anti-inflammatories
C
Chronic pain is best defined (according to newer definitions) as
a. Anything but acute pain
b. Pain that is aching burning or pinching
c. An inability of the nociception system to return to lower, normal modes of functioning
d. Pain that lasts longer than 7 days
e. Pain that is old and longstanding
C
As the dorsal horn becomes changed secondary to either unmitigated pain impulses or unusually large (high intensity, large tissue damage area, etc) pain input, its “windup” makes altered states of functioning more likely. These “altered pathologic states of functioning” (largely due to changed cells in the spinal cord) are knowns as modes:
a. II and III
b. III and IV
c. I and V
d. II and V
e. I and II
B
True or false: Both allodynia and hyperalgesia occur because of sensitized peripheral nociceptors which are allowed ongoing transduction. Allodynia is an exaggerated response to a normally noxious stimulus.
TRUE
The five steps in the nociceptive process in their order of occurance from distal to proximal are:
a. Transduction, transmission, translation, perception and cognition
b. Transmission, transduction, translation, perception and cognition
c. Projection, perception, transmission, transduction and cognition
d. Transduction, transmission, modulation, projection and perception
e. Transmission, transduction, modulation, perception and projection
D
True or false: Serum biomarkers and physiologic parameters are able to confirm presence or absence of pain in both dogs and cats.
FALSE
Although pain score systems numbered from 1 to 10 are common in practice, all of the following are problems with why they frequently don’t work well for cats and dogs EXCEPT:
a. They are variable between staff
b. They are unidimensional and cats/dogs frequently exhibit pain on emotional/behavioral, physical, physiologic and evolutionary (multidimensional) basis
c. They miss the minor details (the trees of the forest) of pain in patients
d. They do not show the large picture (the forest for the trees)
e. They don’t propagate continued care of the patient like quality score systems do
E
What 5 drugs inhibit perception of pain?
- anesthetics
- opioids
- alpha-2 agonists
- benzodiazepines
- phenothiazines
What 8 drugs modulate the spinal pathway to inhibit central sensitization to pain?
- local anesthetics
- opioids
- alpha-2 agonists
- TCAs
- cholinesterase inhibitors
- NMDA antagonists
- NSAIDs
- anticonvulsants
What 2 drugs inhibit transmission and impulse conduction related to pain?
- local anesthetics
- alpha-2 agonists
What 4 drugs inhibit transduction and peripheral sensitization of nociceptors?
- local anesthetics
- opioids
- NSAIDs
- corticosteroids
