Pain II Flashcards
What is the difference between primary and secondary hyperalgesia?
Primary = in the periphery Secondary = at the spinal cord
What are the two fibers that play a role in nociception?
A-delta
C fibers
What is the role that a-delta fibers play a role in? What do they respond to?
Sharp, first pain
Respond to intense mechanical
What is the role of the C fibers? What do they respond to?
Mediate poorly localized, diffuse secondary pain
Polymodal response
What are the three fiber types that are activated in response to pain, in order?
- A-alpha
- A-delta
- C fibers
What are the fibers that are found in the cutaenous tissue?
A-delta
C fiber
What are the fibers that are found in the joints?
A delta C fibers (more here)
Which are more prominent in joints: c fibers or a delta?
C fibers
What are the types of fibers found in muscles?
Similar to joint:
A-delta and C fibers, with x2 more C fibers
What are the types of fibers found in visceral structures?
C fibers
Where does spinal modulation occur?
Dorsal horn of the spine (substantia gelatinosa)
What is the route of innervation of pain (second and first order neurons)?
Spinothalamic pathway
DRG, then substantia gelatinosa, anterior white commissure, and up to the thalamus
What are the fibers found in lamina I and V? What type of pain is this associated with?
A-delta fibers–fast, acute pain
What are the fibers that are found in lamina V? What type of stimuli do these respond to?
Wide dynamic range fibers
Respond to noxious and non-noxious stimuli
What are the fibers that are found in lamina II and III? What type of pai is this associated with?
C fibers–slow, chronic pain
What are the wide dynamic range fibers? What fibers do they synapse with?
Polymodal neurons in lamina V that respond to A-alpha, A-beta, A-delta , and C fibers
What is the major neurotransmitter that is involved in pain transmission?
Glutamate
What are the receptors that respond to glutamate? Which response to substance P?
AMPA and NMDA receptors
NK1 for substance P
Which fiber type has the lowest threshold?
A-beta fibers
What is secondary hyperalgesia?
Prolonged and increased activation of nociceptors in the periphery and projection pathways at the spinal cord
What is the molecular basis for central sensitization or secondary hyperalgesia? (what is the primary neurotransmitter/receptor combination involved in the pain pathway? What happens to the receptor when the signal is prolonged/strong enough?)
Pain signal from neurons releases Glutamate, which activates AMPA receptor.
AMPA receptor will activate NMDA receptor, causing rush of Ca into cell, and “wind up”
What is neuronal plasticity?
Modulation of intracellular signaling and changes in gene expression
What is the chemical basis for chronic pain?
Exaggerated release of glutamate and substance P that results in increased gene expression of pain signals
What is allodynia?
Pain resulting from a non-noxious stimulus (sunburn)
What are the fibers in the DC/ML pathway? (1)
A-beta
What are the fibers in the AL system? (2)
C fibers and A-delta fibers
What is the major pathway that pain travels through? What type of fibers are utilized here?
Neospinothalamic tract–a-delta fibers
Where does the neospinothalamic tract arise from, and terminate?
Arises from lamina I, IV, V goes to VPL nucleus of the thalamus
Where does the VPL nucleus of the thalamus send projections to?
Primary somatosensory cortex
What type of information travels through the neospinothalamic tract?
Sharp pain, with sharp localization
What type of fibers are utilized by the paleospinothalamic tract?
C fibers
Where does the paleospinothalamic tract begin and terminate?
Begins in Lamina II, III, V
Ends in the limbic system
What type of pain information comes from the paleospinothalamic tract? What is the quality of pain sensed through this tract?
Emotional response to pain
Dull, throbbing pain
What is the function of the spinoreticular tract?
Descending pain control and motor response
What is the function of the spinomesencephalic tract?
Descending pain control
Regulates pain experience
What is the function of the superior colliculus with the spinomesencephalic tract?
eye movement toward site of injury
What is the tract that is utilized for the sensory/discriminative component of pain?
Neospinothalamic tract
What is the tract the is utilized for the emotional component of pain?
Paleospinothalamic tract
What is the route of innervation from the VPL nucleus of the thalamus to the prefrontal cortex? (5)
- Primary somatosensory
- Somatosensory association cortex
- Insular cortex
4, Anterior cingulate cortex - prefrontal cortex
What is the function of the anterior cingulate cortex in pain?
Attention part of the pain
Where do signals that go from the spinal cord to the amygdala go?
Prefrontal cortex
Where do signals that go from the spinal cord to the dorsomedual nucleus thalamus go?
Anterior cingulate gyrus to prefrontal cortex
What are the five things that the pain matrix contributes to pain?
- Threatening visual and auditory cues
- Memory of pain
3 Anticipation - Attention
- Empathy with others
What are the two areas in the brain that are most active during pain and are the main parts of the pain matrix?
Insula and anterior cingulate cortex
When is the ACC active in pain? (3)
Perception of pain
Imagining pain
Observation of pain
What is the function of the insula in pain?
Relay station to the limbic system and hypothalamus
What is the gate control theory? How does it work?
C fibers can be deactivated by competition from the A beta fibers
because A beta fibers are faster, and stimulate an inhibitory interneuron
What are the three areas of the brain that are a part of the descending pain control?
- Periaqueductal gray
- Rostral ventral medulla
- Locus coeruleus -pons in brainstem
What drugs utilized the descending pathway of pain control?
Opioids
What is the role of the amygdala in pain perception?
Assigning a negative context to pain
What is the role of the prefrontal cortex in the pain pathway?
Cognitive experience of pain
What is the nucleus in the pons that plays a role in descending pain control?
Nucleus raphe magnus
What is the role of the ventrolateral PAG?
Sympathetic inhibition
What is the role of the dorsal PAG?
Sympathetic excitation–prepares for fight or flight
Which is blocked by naloxone: the ventrolateral or the dorsal PAG?
Ventrolateral
What is the MOA of the ventrolateral PAG?
Nonselective inhibition of A and C fiber input
What is reflective pain?
Pain that is Perceived at a location other than the site of the painful stimulus
What is convergence of pain?
somatic and visceral pain fibers converge on the same secondary afferents in the dorsal horn, causing referred pain
What is projected pain?
Stimulation of a nerve along its path, causing pain in the areas that is innervates distally (hitting ulnar nerve at the medial epicondyle of the humerus
What is the MOA of phantom pain?
Reorganization of the neurons in the spinal cord or brain
What is complex regional pain syndrome?
Continuous burning pain long after seemingly trivial injuries
What is the treatment for complex regional pain syndrome?
Sympathectomy or sympathetic nerve block
What is central pain? What type of pain is this characterized as?
‘pain’ originating from a central process. A form of
neuropathic pain.
What are the symptoms of thalamic pain?
Severe pain to the entire contralateral side of the body
What are the nociceptive specific neurons?
Neurons in laminas I, II, and III that receive only noxious input
Which is wider: primary or secondary hyperalgesia?
Secondary
What is the “wind up” phenomenon?
Activation of the NMDA receptor, causing Ca to rush in and activate lots of pain stuff
What is the cause of allodynia?
WInd up effect
What is the MOA of opioids?
Release of met-enkephalin on the presynaptic spinothalamic neurons, to
reduce excitability
Which is more laterally located: the neospinothalamic tract, or the paleospinothalamic tract? Which has a smaller receptive field?
Neospinothalamic (for both)
True or false: the DC/ML pathway has nothing to do with pain, only discriminative touch and proprioception
False–carries visceral pain
The nucleus Raphe uses what neurotransmitter?
5HT
The locus ceruleus uses what neurotransmitter?
NE
What is the MOA of the locus ceruleus and Raphe nucleus in the descending pain control system?
Activate inhibitory neurons in the spine
What is the role the PAG plays in the descending pathway?
Activates the Raphe and Locus Ceruleus
What is the gate control theory of pain?
Fast conducting mechanoreceptor activation stimulates an inhibitory interneuron with the primary afferents (a-delta and C fibers) pathway
What is projected pain?
Pain produced by irritation of a axon at an ectopic site (like hitting funny bone)
What is the basis for phantom limb pain?
reorganization of the somatosensory cortex and probably other subcortical areas,
including the spinal cord
What is sympathetic mediated pain?
continuous burning pain that may develop following a
traumatic peripheral injury.
What is required to develop sympathetic mediated pain?
Intact SNS
What is the basis for Sympathetic Mediated Pain (SMP)?
tonic release of NE by a damaged sympathetic fibers can activate/sensitize the nociceptors
eliciting ‘pain’
