Analgesia and Pain Flashcards
pain versus nociception
pain includes perception, nociception does not
what is neuropathic pain
pain caused by a lesion or disease of the somatosensory nervous system.
what is nociplastic pain
pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain.
types of physiologic pain
nociceptive/inflammatory
types of pathophysiologic pain
neuropathic and nociplastic
acute pain is carried by:
Carried by large diameter myelinated Aδ fibers
chronic pain is carried by:
Carried by small diameter non-myelinated ‘C’ fibers
somatic pain involves which fibres? which tissues and what characteristics?
(fibres A-delta)
* Skin, musculoskeletal
* Superficial or deep
visceral pain involves what fibres?
(fibres C)
* Organs
origin of innervcation for visceral vs somatic pain
visceral: spinal and vagal
somatic: spinal
noxious stimulus for visceral vs somatic pain:
visceral: stretch, inflammation, ischemia
somatic: damage (mechanical)
localization of visceral pain vs somatic pain
visceral: poor
somatic: precise
is visceral pain referred? somatic?
visceral: yes
somatic: no
1st ORDER NEURONS go from:
- From NOCICEPTORS to the SPINAL CORD
1st ORDER NEURONS go from:
- From NOCICEPTORS to the SPINAL CORD
TYPES OF STIMULI THAT EXCITE NOCICEPTORS
- Thermal
- Mechanical
- Chemical
fast pain stimuli? what fibres is it carried on?
- Thermal , Mechanical
- A-delta Fibers
slow pain stimuli? what fibres is it carried on?
- All three
- C Fibers
difference in conduction rate between A-delta and C fibres
A-delta are fast, C are the slowest (non-myelinated, very thin)
- A-delta (A-δ) fibers characteristics? what is the neurotransmitter?
- Myelinated
- Fast
- 12-30 meters/sec
- Fast, First pain
- Neurotransmitter is glutamate
C fibers characteristics? what is the neurotransmitter?
- Unmyelinated
- Slow
- 0.5-2 meters/sec
- Slow, Second pain
- Neurotransmitter is substance P and glutamate
where do pain fibres go in the spinal cord?
Dorsal horn:
Aδ fibers
* Laminae I (II is also mentioned)
C fibers
* Laminae I and II
what neurotransmitters are used for transmitting pain information? what is the difference between them?
Glutamate
* Excitatory
* Lasts only for few milliseconds
* Acts very rapidly
Substance P
* Excitatory
* Released slowly over period of seconds or minutes
what is the double pain sensation?
- Glutamate transmitter gives a faster pain
sensation - Substance P transmitter gives more lagging sensation
2nd ORDER NEURONS path:
- From DORSAL HORN of spinal cord, THROUGH TRACTS, to THALAMUS
3 classes of second order neurons. What are they and which are involved with pain?
- Low threshold mechanosensitive neuron (LT)
* Light touch, pressure, proprioception - Nociceptive specific neuron (NS)
* Noxious stimuli (This are the Aδ and C fibers) - Wide dynamic range neuron (WDRN)
* Respond to a wide range of stimulus intensities
from non noxious to noxious
* They respond like C fibers
what is the neospinothalamic tract? what path do the neurons follow? where do they terminate?
What fibres are involved, and what type of pain do they carry?
- 2nd order neurons
- Synapses at Lamina I and some in II
- Long fibres which cross the midline through the anterior commisure and pass upwards in the contralateral anterolateral columns
- Terminate at the ventral area of the thalamus
- This is the classic lateral Spinothalamic tract
- Involves the A-δ fibers
- Sharp/fast/localized pain
- “Direct path” from nociceptor to thalamus, without additional synapses besides the 1st to 2nd order neuron
what tracts are contained in the paleospinothalamic tract umbrella?
- 1) Spinoreticular tract
- 2) Spinotectal or spinomedullary tract
- 3) Spinothalamic tract
type of neurons in the paleospinothalamic tract? where do they synapse and where do they go? what kind of fibres?
- 2nd order neurons
- Synapse in laminae I and then project to IV-VIII (V is most relevant)
- The innervation of these three tracts is bilateral because some of the ascending fibers do not cross to the opposite side of the cord
- Ipsi- and contralateral
- Involves the C fibers
- Slow/dull/diffuse pain
- Multiple synapses along the spinal cord
where do neurons in the archispinothalamic tract synapse? where do they go? what type of fibres are present?
2nd order neurons
* Synapse at laminae II (substantia gelatinosa)
* Then project to laminae IV-VII and ascend to synapse at the mesencephalic reticular formation (MRF) and the periaqueductal gray (PAG)
Involves the C fibers
* Slow/dull/diffuse pain
* Multiple synapses along the spinal cord
of the 3 spinal tracts that carry pain: which carry fast pain, and which carry slow pain?
Neospinothalamic tract for fast pain Paleospinothalamic tract for slow pain Archispinothalamic tract for slow pain
visceral pain is carried in what fibres? in what tracts?
VISCERAL PAIN = C FIBERS
* Paleospinothalamic tract
* Archispinothalamic tract
However, note
* C fibers = Somatic and visceral pain
somatic pain is carried in what type of fibres? in what tract?
- Pricking or fast pain
- Neospinothalamic tract
- Aδ fibers
- Burning pain
- Paleospinothalamic tract * C fibers
- Archispinothalamic tract * C fibers
what tract carries pain from the head, face, and intraoral structures? what is the pathway?
Trigeminal tract
Is also a Neospinothalamic tract
Noxious stimulus is transmitted to trigeminal ganglion
Trigeminal fibers enter the pons, descend to the medulla and synapse in the spinal trigeminal nucleus
Cross midline and ascend as trigeminothalamic tract
what type of fibres are present in the trigeminal tract? where do they go?
Aδ fibers go to ventral thalamus and from there to the somatosensory cortex
Awareness of exact location of pain
C fibers terminate in the parafasciculus and centromedian thalamus (Intralaminar nuclei)
what is the pathway of 3rd order neurons?
- From the THALAMUS to the SOMATOSENSORY CORTEX
where do 3rd order neurons of the neospinothalamic tract go? what do they allow us to do?
- From the thalamus, they communicate with the somatic sensory cortex
- Fast pain can be localized
where do 3rd order neurons of the paleospinothalamic tract go? what do they allow us to do?
- From the parafasciculus and centromedian thalamus (Intralaminar thalamic nuclei), these fibers synapse bilaterally in the somatosensory cortex
- Emotional response to pain
- Visceral response to pain
- Also activates brain stem nuclei which are the origin of descending pain suppression pathway regulating noxious input at the spinal cord level
where do 3rd order neurons of the archispinothalamic tract go? what do they allow us to do?
Ascend to the PF-CM complex (IL) areas of the thalamus and also send collaterals to the hypothalamus and to the limbic system nuclei
* Mediate visceral, emotional and autonomic reactions to pain
what is pain transduction? what affects it?
- Transforms environmental stimuli into an electrical event and generates action potential
- Chemical, thermal, physical noxious stimuli
- Characterized by a stimulus threshold
- Strength and duration of stimulus affects action potential character
do nociceptors adapt to continued pain?
- Adapt very little OR not at all
- Excitation of the pain fibers, becomes progressively greater, as the pain stimulus continues
- Increased sensitivity = hyperalgesia
Nociceptors Aδ and C fibers are carried as SNS or PNS components?
both SNS and PNS nerves have these fibers
what is pain signal modulation? where does this occur?
Peripheral sensory impulses are modified (amplified or suppressed) in the spinal cord by several neurotransmitters
Peripheral ascending, interneurons, descending pathways
Excitatory receptors- facilitate excitatory transmission
* ATP, substance P, prostanoids, glutamate (AMPA, KAI, NMDA)
Inhibitory receptors- inhibit excitatory transmission
PROJECTION AND PERCEPTION of pain signals occurs how? what structures are involved?
- Nociceptive information conveyed to the brain by projection nerve tracts (2nd order neurons)
- RAS (reticular activating system- brainstem) and thalamus are central integrating and transmission points for pain perception and responses
> Cerebral cortex believed vital in integrating pain perception
PAG (periaqueductal gray is key descending modulatory pathway)
* Opioid activation
* Adrenergic activation
* Gabaergic activation
ALLODYNIA
Pain due to a stimulus which does not normally provoke pain
HYPERALGESIA
An increased response to a stimulus which is normally painful
how does peripheral pain sensitization occur?
From tissue damage and inflammation
Neurochemical alterations
how does central pain sensitization arise?
- From frequent (chronic) or severe peripheral nociceptor input
- Spinal and higher CNS uninhibited neuromodulation
> Alterations in dorsal horn excitability
> Long-lasting depolarizations of neurons- “Wind-up” - Recruitment of A-beta fibers
> Normal low-threshold and innocuous stimuli
how does central pain sensitization arise?
- From frequent (chronic) or severe peripheral nociceptor input
- Spinal and higher CNS uninhibited neuromodulation
> Alterations in dorsal horn excitability
> Long-lasting depolarizations of neurons- “Wind-up” - Recruitment of A-beta fibers
> Normal low-threshold and innocuous stimuli
WIND-UP
-SEQUENCE OF EVENTS
Wind-up can happen anywhere in the spinal cord or brain. It means that the pain signal that comes into the central nervous system becomes stronger and longer lasting. This is a physiologic process that involves activation of receptors that are normally dormant on post synaptic nerve endings.
- Build-up of Ca2+ in presynaptic terminal
- Increases neurotransmitter release of aa and Substance P
- Activation of adenosine monophosphate acid (AMPA) postsynaptic receptors and subsequent depolarization releases block of N-methyl-D-aspartate (NMDA) receptors
- Activation of NMDA and NK1 receptors induces long-lasting cumulative depolarization
- Cytosolic Ca2+ increases due to entry through the NMDA ionophore.
- Enhanced performance of NMDA receptors through the increased Ca2+ concentration and the activation of NK1 receptors through second messenger systems
- All induced changes result in production of action potentials and wind-up
FIBERS AFTER NERVE INJURY
Aβ transmission is coupled with C fibers
> Touch stimulus is interpreted as noxious
* Allodynia
Due to:
1. sprouting of fibers into laminae II and/or
2. Loss of fiber sheath allows contact with denuded fibers facilitating electrical and chemical cross-excitation, and/or
3. During healing Aβ fibers connect with C fibers
Result at the dorsal root ganglion for Aβ :
Express substance P in lamina II and activation of NK1 receptor
NEUROPATHIC PAIN is what? arises from what?
- Sharp, shooting, devastating, persistent pain
- Arises from functional changes occurring in the CNS secondary to peripheral nerve injury
- Once the nerve is damaged, the damaged nerve elicits sustained activation of nociceptors and/or nociceptive afferents
- The neuropathic pain is due to an abnormal activation of the nociceptive system without specifically stimulating the nociceptors
