Physiology of Pain Flashcards
2 Types of Pain:
Acute (somatic and visceral)
Chronic
Acute Pain
- caused by noxious stimuli (nociceptive pain) and is a SYMPTOM
- self-limited, resolves in days-weeks
- Somatic: superficial (skin = sharp)
Visceral: internal organ (hard to identify = referred)
Chronic Pain
- persists beyond “normal” time for pain
- starts 6 weeks to 3 months post op
- lasts 1-6 months or longer
- nociceptive; neuropathic; cancer; unk etiology
Acute Pain 2
Result of tissue damage and is a symptom.
- well defined onset, clear pathology
- protective from tissue damage, allows healing time
- observable tissue damage present
- tx w pharmacologic means
- acute pain is useful and protective… chronic pain is NOT!
Risk Factors for Increased Post Op Pain
- poor pain control w prior surg
- pain lasting >1 month
- psychologically vulnerable
- young pts
- female
- workman’s comp
- genetics (cultural, pharmacogenomic issues)
- diffuse noxious inhibitory control issues
- chronic opioid use
- physical dependence tolerance
Diffuse Noxious Inhibitory Control Issues (DNIC)
- noxious stimuli activate C and A delta fibers
- DNIC is where WDR neurons responsive to pain signals from one area may be inhibited by stimuli from another location
Compared to Opioid-Naive Patients, Pain is…
- pain is 3x higher
- post op opioid use is 3x higher
- if epidural is placed, it stays in for 3 extra days
Independent Predictors for Development for Persistant Postsurgical Pain (PPP)
- preop pain (those on opioids require more pain mgmt)
- age (younger is worse)
- type of surgery
- preop anxiety
- severity of immediate post op pain
- size of incision (larger = more pain)
- gender (femals > males)
- need for information
Independent Predictors that do NOT indicate Development for Persistant Postsurgical Pain (PPP)
- BMI has inconsistent effects
- duration of surgery
- type of anesthesia (regional vs general has no effect on pain)
Problems w poorly treated post-op pain
- increased risk of PPS (persistant postsurgical pain)
- increased CV complications
- increased pulm complications
- delays discharge
- prolongs convalescent leave and return to work
- increased risk of admission after ASC procedures
Model of Pain Transmission
- Pain impulse enters dorsal horn
- Glutamate or Substance P allow transmission (intrathecal morphine inhibits release of Sub. P into CSF)
- Transmission may be modulated by a descending inhibitory pathway that inhibits excitatory neurotransmitter (opioid receptors in substantia gelatinosa are probalby on Sub. P terminals and block its release, producing analgesia!)
NE is an ______ transmitter in the pain pathways
inhibitory
Non-Opioid Inhibitory Transmitters
- endorphins
- serotonin
- NE
- glycine
- GABA
Clonidine is a _______ and produces ______ _______.
Clonidine is an alpha-1 agonist and produces spinal analgesia.
Neurotransmitters: Neuropeptides
- substance P and calcitonin
- opioids
- glutamate
- ion channels
Substance P and Calcitonin
neuropeptide neurotransmitters
- Calcitonin Gene Related Peptide (CGRP)
- inflammatory response = arthritic pain
Opioids
Neuropeptide Neurotransmitters
- after peripheral inflammation there is an unregulation of the opioid receptors on the peripheral terminals of primary afferents
- macrophages, monocytes, and lymphocytes all contain endogenous opioids
Glutamate
Neuropeptide Neurotransmitter
- excitatory neurotransmitter
- receptors found on primary afferent nociceptor terminals
- injection of glutamate = hyperalgesia
- upregulated in joints after inflammation
- blockade of receptors = reduces pain and hyperalgesia
Injection of glutamate = ______
Blockade of gluatmate receptors = _______
Injection of glutamate = hyperalgesia
Blockade of gluatmate receptors = reduces pain and hyperalgesia
Ion Channels
Neuropeptide Neurotransmitters
- acid sensing channels = low pH in inflamed tissues
- vanilloid rexeptor activated by capsaicin and mediates hyperalgesia
Excitatory Neurotransmitter Effects on Pain:
Gluatmate
- located in hippocampus, cerebral cortex, and substantia gelatinosa
- learning and memory (recall)
- central pain transduction
- excitotoxic neuronal injury
Ionotropic Gluatmate Receptors:
NMDA
- ligand operated channel opens, influx of cation Na+, membrane depolarization
Inhibitory Neurotransmitters
- GABA
- ACh
- Dopamine
- Epi and NE
- Glycine
- Endorphins
- Serotonin
- Histamine
GABA
- inhibitory NT
- located in cortex, basal ganglia, cerebellum and SC
- increase Cl- which HYPERpolarizes
Glycine
- inhibitory NT
- located in SC
- increases Cl- which HYPERpolarizes
- strychnine and tetanus antagonize glycine’s postsynaptic inhibition which = sz activity
- glycine solution used in TURPs may result in visual disturbances post-op d/t retinal inhibition
ACh
Inhibitory NT
- increased K+ conductance in peripheral PNS
Dopamine
- inhibitory NT by working on adenylate cyclase
NE
inhibitory NT in RAS & hypothalamus
EPI
inhibitory NT in hypothalamus
Endorphins
- inhibitory NT by being excitatory for th edescending pathways that inhibit pain transmission
Serotonin
- inhibitory NT in brain (ketamine may act on serotonin)
Histamine
Inhibitory NT in hypothalamus and RAS
Where do pain receptors (nociceptors) originate?
- skin
- skeletal structures
- viscera
3 Neuron System
- primary afferent
- spinothalamic tract
- thalamocortical neuron
Excitatory Neurotransmitters
- substance P (NK-1 receptors)
- bradykinin
- glutamate (NMDA and AMPA receptor)
- calcitonin gene related peptide (CGRP)
A-Delta fibers
myelineated, fast pain!
- primarily releases glutamate which binds to AMPA and NMDA receptors
- usually incisional pain or pain that causes rapid withdrawal of extremity from stimuli
C-fibers
non-myelineated, slow, nagging pain
- primarily relase substance P** which binds to **NK-1 receptors in the postsynaptic membrane
- punch in the thigh, aching days later
- slow in intensity, guarding effect
Transmission of Pain
Flaccid paralysis and absent stretch reflex indicate….
lower motor neuron lesion/injury
Spastic paralysis with accentuated stretch reflex in the absence of skeletal muscle paralysis indicates…
upper motor neuron injury/destruction
1st Generation Na+ channel blockers (fast pain, A-delta fibers)
disrupt transmissin
carbamazepine (Na)
Phenytoin (Na, K, GABA, Ca)
Valproic Acid (Na, K, GABA, Ca)
2nd Generation Na+ channel blockers (fast pain, A-delta fibers)
oxcarbazepine (Na, Ca, K)
lamotrigine (Na, Ca, K, GABA)
topiramate (Na, Ca, GABA, glutamate)
Drugs that block Ca+ Channels (slow pain, C-fibers)
gabapentin
pregabalin
How do opioids block the VGaCa++ Channels?
- enhance K+ efflus and enhance noradrenergic activity at the dorsal horn
- alters the perception of pain (not blocking pain)
- modulates nociceptive pathways and enhances endogenous opioids
- mesolimbic dopamine system = reinforcing and rewarding properties
Common Dermatome Levels
C4 - clavicle
T4 - nipples (and chemo. trigger zone)
T6 - xiphoid
T10 - umbilicus
T1 - T12 - SNS (sympathetic chain)
S2-4 - perineum
L4-5 - tibia
