neurobiology of pain Flashcards
what is pain
An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage or described
in terms of such damage.
what is pain classified by (4)
- underlying etiology
- anatomic location
- temporal nature
- intensity
what is included in underlying etiology
- nociceptive: tissue damage/injury ( incision post op fracture)
- inflammatory: infection and inflammation
- Neuropathic: nere damage/injury
what is included in anatomic location
somatic visceral
what is the duration of accute and chronic pain
acute < 3 month
chronic >= 3 months
what are the different classification of pain intensity
Mild:1-4
Moderate 5-7
Severe 8-10
what is nociceptive pain
- examples
- the result of direct tissue injury from a noxious stimulus.
- Examples include bone fracture, new surgical incision, and acute
burn injury
what is inflammatory pain
- examples
result of released inflammatory mediators that activates nociceptors
* Examples include appendicitis, meningitis, rheumatoid arthritis, inflammatory bowel disease
what is neuropathic pain
-examples
- the result of injury to nerves leading to an alteration in sensory transmission. It can be central or
peripheral in nature. - Examples include diabetic peripheral neuropathic pain, postherpetic neuralgia, chemotherapy induced pain, and ”sciatica
what is acute pain
- examples
- lasting less than three monthss and is a neurophysiological respone to noxious injury
- resolves with natural healing
-post-operative pain, fractured bones, appendicitis,
crush injury to finger
what is chronic pain
- examples
is defined as lasting more than 3 months(usually beyond the expected course of an acute
disease or after complete tissue healing).
* Examples include low back pain, most neuropathic pain syndromes,
and chronic pancreatitis.
what is acute on chronic pain
- examples
times of acute exacerbations
of a chronic painful syndrome or new acute pain in a person
suffering from a chronic condition.
- Examples include a sickle cell exacerbation in a patient with sickle
cell disease or an abscess in a patient with sickle cell disease.
how is pain intensitydetermined
- by pain assesment scores in combination with history and physical exam
- is subjective
what are pain scales used for
Pain Scales are used to assess and quantify the intensity of a patients pain.
Remember that each scale has its’ own scoring range and levels
for mild, moderate or severe pain intensity.
pain is part of ______ ______
normal sensation
what is the pain pathway
where the cell bodies of pain sensing neurons ( nociceptors)
- in the DRG
Aδ and C DRG neurons are ____
nociceotors
what type of neurons are Aδ and C nociceptors
They are Pseudounipolar neurons which has one extension
from its cell body and split into two branches.
what do the peripheral and central branches of Aδ and C DRG neurons do
Peripheral branches send free nerve endings to end organs
such as skin, muscle, joints, viscera, dura and blood vessels.
* Central branches form dorsal roots entering spinal cord dorsal
horn, synapse on Secondary sensory neurons.
what is the size of Aδ nociceptors, do they have mylintions?
what do they respond to
- Aδ nociceptors are small-medium neurons with thin myelinated
axons (fibers) - Aδ nociceptors respond to mechanical or mechanical/thermal
stimuli
what is the size of C nociceptors, are they mylinated?
- what do they respond to
- C nociceptors are small neurons with unmyelinated axons
- C nociceptors respond to mechanical, thermal and chemical stimuli
what dype of pain is the A and C noniceptors
- A: fast and sharp pain - high conduction velocity
- C: slow, aching pain - slow conduction velocity
both A and C nociceptors send ______ branches which eventually form _____ _____ _____ in end of organs such as ___ ____ ____
- peripheral branches
- free nerve endings
- skin, muscle , joints
what are free nerve endings called and why
Free Nerve Endings are called “cutaneous nociceptors” since they are
the ones who directly receive external painful (noxious) stimuli.
what are the classificatons of of cutaneous nociceptors
- Mechanical Nociceptors: respond to mechanical damage, Aδ
- Thermal Nociceptors: respond to temperature extremes, Aδ
- Mechano-thermal Nociceptors: respond to both mechanical and
temperature stimuli, Aδ - Polymodal Nociceptors: respond to mechanical, thermal and
chemical stimuli, C
transduction of pain signals
- Noxious stimuli activated cutaneous nociceptors.
- Signals are transmitted to cell bodies of nociceptors located in DRG
to activate nociceptors. - Action potentials are produced in nociceptors.
- Electrical signals are then transmitted through central
branches to spinal dorsal horn to activate the secondary
neuron
why can cutaneous nociceptors sense pain stimuli
special receptors or
ion channels expressing on cutaneous nociceptors respond to
different external stimuli.
what are the VR1, CMR1 , ASIC receptors and what do they respond to
transmission of pain signals
-* Electrical signals are transmitted to the secondary order neurons
in spinal cord dorsal horn
* C afferent fibers mainly terminate in superficial gray matter
laminae I-II of the spinal cord
* Aδ afferent fibers terminate in both superficial (I) and
deep (V) laminae.
what are the major transmitters involved in pain signal transmission
- EAA: glutamate, aspartate
- Substance P (neuropeptide)
- Calcitonin gene related peptide
(CGRP)
pain sensation: reffered pain
how is pain from visceral nociceptors localized
- how it can it be felt as
- poorly localized
- felt as pain on surface areas
how are pain signls carried out to different reigons through the brain
- asceding pathways
what are the 2 different ascending pathways
Lateral Pathways – Spinothalamic tract (to contralateral lateral
thalamus, then SI and SII cortex) transmits discriminative
information about the location, quality, and intensity of noxious
input.
* Medial Pathways – Spinoamygdalar, spinohypothalamic, medial
spinothalamic, spinoreticular and other spinolimbic tracts. They
activate affective, alerting, motivational, autonomic and escaperesponses to pain (suffering, anxiety, increased attention and
arousal, memory, increased heart rate and blood pressure).
which aras of the brain are activated by noxious stimulation
- different cortical and subcortial areas
Modulation: inhibition
when are inhabiatory mechanisms activated
during transmission of pain
signals to terminate or reduce pain sensation.
what do descedning pathways do
- where do they originate
Descending pathways inhibit pain activation. The system
originates from cortex, thalamus, midbrain (periaqueductal grey)
and brainstem (rostral ventromedial medulla, dorsolateral pons).
They send axons to spinal dorsal horn and inhibit pain signal
transmission.
what are the neurotransmitters of modualtion/inhibition
Main neurotransmitters: norepinephrine,
serotonin,
dopamine
endogenous opioids
gate control - spinal mechanism
what is the trigeminal nerve
- what type of fibers does it contain
- the largest cranial nerve, resposible for sensation in the face
- contain sensory and motor fibers
what are the three branches of the trigeminal nerve
V1: Ophthalmic branch, sensory
V2: Maxillary branch, sensory
V3: Mandibular branch, sensory and motor
where is the trigeminal ganglion located
- depression in the middle cranial fossa
what is the importance of the trigmeinal ganglion.
contains cellbodies:
1) whose dendrites carry sensations from the face
2) whose axons form the sensory root of the trigeminal nerve
how many niclei in the trigeminal nuclei
- 4 ( 3 sensory and 1 motor)
what are the general somatic affernt nuclei
what are the special viceral effernt nuclei ?
- what does it supply
what is the ascending patheay for orofacial pain
- pain signals from the face are carried to thalmis through the trigeminothalamic tract
- thalmic projections to sensory cortex corresponding to face area
- secondary axons from TN project to insula basal ganglia, anterior cingulate cortex, parabrachial area, anygdala,limbic circuitry
what is trimenial neuralgia
what is trigeminal neuralgia charecterized by?
- what nerves does it involve
nerve innervation of teeth :
what innervates the odontoblastic layer of the pulp
- how do they enter
-what do they further branch into
Sensory nerve fibers originating from Superior and Inferior
alveolar nerves innervate the odontoblastic layer of the pulp
cavity
* These nerves enter the tooth through the apical foramen
* They further branch to form sub odontoblastic Nerve Plexus of
Raschkow
what do the nerve plexus of Raschkow contact
odontobalsts
what do the apical extentsions of odontoblasts enter
the dentinal tubules
what is the hydrodynamic theory
the most popular theory to
explain dentine hypersensitivity.
what is included in the hydrodynamic theory
- Different types of stimuli ace on exposed dentine
- Increase fluid flow through the dentinal tubules
- Activate mechanoreceptors on the pulp nerves
Special receptors and ion channels expressed on Odontoblast and
nerve endings also respond to _______ _______
external stimuli
what are target peripheral nociceptors
local anesthetics
anti-inflammatory drugs
what is included in local anesthetics
– lidocaine, bupivacaine – blocking sodium
channels
what is included in anti-inflammatory drugs
NSAIDS – inhibiting cyclooxygenase
(Cox1 and Cox2) to reduce inflammatory mediators such as
prostaglandins
Target pain transmission centrally by:
- anti depressants
- opiods
- anti convulsants
examples of antidepressants and what do they do
SNRI, SSRI, NRI, TCA – boosting
serotonin and/or norepinephrine levels to activate descending
inhibitory pathway
what are examples of opioids and what do they do
morphine, oxycodone – activating opioid receptors to
reduce pain transmission (spinal and supra spinal levels)
what are examples of anti convulsants and what do tbey do
carbamazepine, topiramate, valproic acid,
gabapentinoid – blocking central sodium or calcium channel
