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
pain can be classified by:
- underlying etiology
- anatomic location
- temporal nature
- intensity
underlying etiology can be
- nociceptive
- inflammatory
- neuropathic
anatomic locations of pain:
- visceral
- somatic
duration of pain:
acute
chronic
acute on chronic
pain instensities
- mild (1-4 ratings)
- moderate (5-7 ratings)
- severe (8-10 ratings)
nociceptive pain
- the result of direct tissue injury from a noxious stimulus
- ex: bone fracture, new surgical incision, and acute burn injury
inflammatory pain
- the result of released inflammatory mediators that activates nociceptors
- ex: appendicitis, meningitis, rheumatoid arthritis, inflammatory bowel disease
neuropathic pain
- the result of injury to nerves leading to an alteration in sensory transmission
- can be central or peripheral
- ex: diabetic peripheral neuropathic pain, postherpetic neuralgia, chemotherapy induced pain, and sciatica
acute pain
- lasts less than 3 months
- neurophysiological response to noxious injury that should resolve with normal healing
- ex: post-op pain, fractured bones, appendicitis, crush injury to finger
chronic pain
- lasts more than 3 months
- beyond expected course of an acute disease or after complete tissue healing
- ex: low back pain, most neuropathic pain syndromes, and chronic pancreatitits
acute on chronic pain
- times of acute exacerbations of a chronic painful syndrome or new acute pain in a person suffering from a chronic condition
- ex: sickle cell exacerbation in a patient with sickle cell disease or an abcess in a patient with sickle cell disease
pain intensity is determined by
- pain assessment scores
- combined with history and physical exam
- subjective
pain is part of _________ sensation
normal
pain sensation
- sensory receptor detects stimulus
- sensory neuron conduct nerve impulse to spinal cord then to brain or straight to brain
- brain interprets
- brain’s interpretation of the info is a perception or understanding of the stimulus
nociceptors
cell bodies of pain sensing neurons
where are nociceptors located
DRG
A(theta) and C DRG neurons are types of
nociceptors
A(theta) and C DRG neurons
- pseudo-unipolar neurons which has one extension from the cell body and split into 2 branches
- peripheral branches send free nerve endings to end organs (skin, muscle,)
- central branches from dorsal roots entering spinal cord dorsal horn, synapse on secondary motor neurons
A(theta) nociceptors
- small-medium neurons
- thin myelinated axons
- respond to mechanical/mechanothermal stimuli
C nociceptors
- small neurons
- unmyelinated axons
- respond to mechanical, thermal, and chemical stimuli
A(theta) fiber has ________, _______ pain
fast, sharp
C fibers have ______, ___________ pain
slow, aching
A(theta) and C nociceptors send
peripheral branches (fibers) that form free nerve endings
free nerve endings (cutaneous nociceptors)
- receive directly external painful stimuli
cutaneous nociceptors are classified by responses:
- mechanical
- thermal (temp extremes)
- mechano-thermal
- polymodal (mechanical, thermal, and chemical stimuli)
fibers and nerve endings
transduction of pain signals
- noxious stimuli active cutaneous nociceptors
- signals transmitted to cell bodies of nociceptors in DRG to activate nociceptors
- AP are produced in nociceptors
- electrical signals are then transmitted through central branches to spinal dorsal horn to activate the secondary neurons
why cutaneous nociceptors can sense pain stimuli?
special receptors or ion channels expressing on cutaneous nociceptors respond to different external stimuli
2021 nobel prize in physiology or medicine was for
discovery of receptors for temp and touch
transmission of pain signals
- electrical signals are transmitted to secondary order neurons in spinal cord dorsal horn
- C afferent fibers mainly terminate in superficial gray matter laminae I-II of the spinal cord
- A(theta) afferent fibers terminate in both superficial and deep laminae
major neurotransmitters involved in transmission of pain signals
- EAA: glutamate, aspartate
- Substance P (neuropeptide)
- calcitonin gene related peptide (CGRP)
pain sensation: referred pain
- pain from visceral nociceptors is poorly localized
- can be felt on surface areas
- knowledge of referred pain maps important in clinical diagnosis
- somatic and visceral afferents may converge on same 2nd order neuron
transmission (cont)
- pain signals are carried out to different brain regions through ascending pathways
- lateral pathways
- medial pathways
lateral pathways
spinothalamic tracts
- transmits discriminative info about the location, quality, and intensity of input
medial pathways-
- spinoamygdalar tract
- spinohypothalamic tract
- medial spinothalamic
- spinoreticular
- other spinolimbic tracts
- activate affective, alerting, motivational, autonomic and escape responses in pain (suffering, anxiety, increased attention, arousal, memory, inc. heart rate, BP)
different cortical and subcortical areas are activated by noxious stimulation to produce:
- pain sensation
- emotional
- cognitive reactions
modulation: inhibition
- inhibitory mechanisms are activated during transmission of pain signals to terminate or reduce pain sensation
- descending pathways inhibit pain
how do descending pathways inhibit pain?
- originates in cortex, thalamus, midbrain (periaqueductal gray) and brain stem
- send axons to spinal dorsal horn and inhibit pain signal transmission
main neurotransmitters of pain inhibition
- norepinephrine
- serotonin
- dopamine
- endogenous opioids
descending inhibitory pain pathway
gate control
theory that offers a physiological explanation for the previously observed effect of psychology of pain perception
- inhibited pain signals by activating inhibitory pain neurons
orofacial pain
trigeminal nerve contributes to a lot of orofacial pain
trigeminal nerve
- largest CN
- sensory and motor
- 3 branches (opthalamic, maxillary, mandibular)
trigeminal ganglion
- site: occupies a depression in the middle cranial fossa
- importance: contains cell bodies whose dendrites carry sensations from the face and the axons form the sensory root of the trigeminal nerve
4 nuclei of trigeminal nerve
- mesencephalic
- principal
- spinal
- motor
mesencephalic nucleus
- midbrain and pons
- receives proprioceptive fibers form face
principal (main) sensory nucleus
- pons
- receive touch fibers from face
spinal nucleus
- pons, medulla, and upper 2-3 cervical segments of spinal cord
- receives pain and temp from face
motor nucleus
- pons
- 4 muscles of mastication
- other 4 muscles (ant. belly of digastric, mylohyoid, tensor tympani, and tensor palati)
ascending pathways for orofacial pain
- pain signals from face are carried to thalamus thru trigeminothalamic tract, mostly crossed
- thalamic projections go to sensory cortex corresponding to face area
- secondary axons from TN project to insula basal ganglia, anterior cingulate cortex, parabrachial area, amygdala, limbic circuitry
trigeminal neuralgia
- compression, degeneration or inflammation of 5th CN may result in this (tic douloureux)
- characterized by episodes of intense stabbing, excoriating pain radiating from angle of jaw along a branches of the trigeminal nerve
- usually involves maxillary and mandibular nerves
- rarely in ophthalmic division
trigeminal neuralgia image
treatment of trigeminal neuralgia
1st: pain meds
2nd: stronger meds
3rd: surgery
alternate: other meds
nerve innervation of teeth
- nerves originate from superior and inferior alveolar nerves
- innervate odontoblastic layer of pulp cavity
- enter tooth by apical foramen
- branch to form sub odontoblastic nerve plexus of raschkow
hydrodynamic theory
- explains dentine hypersensitivity
- different types of stimuli are on exposed dentine
- increase fluid flow through the dentinal tubules
- activate mechanoreceptors on the pulp nerves
special receptors and ion channels expressed on ____________ and _________ ___________ also respond to external stimuli
odontoblasts, nerve endings
pharmacological treatment of pain
- target peripheral nociceptors
- target pain transmission centrally
target peripheral nociceptors
- local anesthetics (lidocaines, bupivacaine): block sodium channels
- anti-inflammatory drugs (NSAIDS): inhibit cyclooxygenase (COX1 COX2) to reduce inflammatory mediators such as prostaglandins
target pain transmission centrally
- antidepressants (SNRI, SSRI, NRI, TCA): boosting serotonin and /or norepinephrine levels to activate descending inhibitory pathway
- opioids (morphine, oxycodone): activating opioid receptors to reduce pain transmission (spinal and supra spinal levels)
- anti-convulsant (carbamazepine, topiramate, valproic acid, gabapentinoid): block central Na or Ca channels
