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PMCOL 412 > PAIN II > Flashcards

PAIN II Flashcards

1
Q

Pathway to brain

A

Most axons of lamina I and IV projection neurons cross midline and ascend in the anterolateral quadrant of SC

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2
Q

Terminations of pain pathways and their tract

A
  • Reticular Formation (Spinoreticular Tract)
  • Midbrain (Spinomesencephalic Tract)
  • Thalamus (Spinothalamic Tract)
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3
Q

Spinoreticular Tract projects to

A

reticular neurons (alerts to pain) in brainstem

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4
Q

Does the Spinoreticular Tract have topographical organization

A

NO–Lacks topographical organization

reticular neurons have wide receptive field

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5
Q

What aspects of pain are signalled by the Spinoreticular Tract

A

general aspects of pain perception

e.g. alerts onset of pain–doesn’t say what or where BUT ALERTS to pain

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6
Q

reticulothalamic tract

A

Projection from reticular formation to thalamus (second to the spinoreticular tract)

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7
Q

Spinomesencephalic tract–projects to

A

midbrain periaqueductal gray matter (PAG)

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8
Q

Role of the PAG

A

interaction between ascending pain signals and descending analgesic information from `emotional centres’ such as amygdala

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9
Q

Spinomesencephalic tract–additional projections

A

to hypothalamus (lateral parabrachial area), nucleus of solitary tract and amygdala

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10
Q

Role of Spinomesencephalic tract

A

Autonomic, affective and neuroendocrine responses to pain

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11
Q

Spinothalamic tract: 2 divisions

A

Lateral–NEW; to VPL

Medial–OLD: to intralaminar thalamic neurons

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12
Q

Spinothalamic tract (lateral division) is ___ (new or old)

A

NEW; Phylogenetically recent = neospinothalamic tract

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13
Q

Lateral Spinothalamic tract projects to

A

ventroposteriolateral (VPL) nucleus of thalamus–only 10% of these neurons are nociceptive

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14
Q

Role of the lateral spinothalamic tract

A

somatotopically organized

localization and discriminative aspects of pain

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15
Q

Further projections of the lateral spinothalamic tract

A

somatic sensory cortex and parietal lobe

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16
Q

Spinothalamic tract (medial division) is ___ (new or old)

A

OLD; Phylogenetically old = paleospinothalamic tract

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17
Q

Medial Spinothalamic tract projects to

A

intralaminar thalamic neurons

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18
Q

Medial Spinothalamic tract organization and input

A

NOT somatotopic organization

input comes from dorsal horn cells have large receptive fields

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19
Q

Further projections of the Medial Spinothalamic tract

A

project widely to association and prefrontal cortex

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20
Q

Role of the Medial spinothalamic tract

A

affective and alerting aspects of pain

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21
Q

This tract alerts you to pain

A

Spinoreticular tract

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22
Q

This tract is repsonsible for the autonomic, affective and neuroendocrine responses to pain

A

Spinomesencephalic tract

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23
Q

This tract is somatotopically organized and is responsible for localization and discriminative aspects of pain

A

Lateral division of the spinothalamic tract

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24
Q

This tract has affective and alerting aspects to pain and projects to the prefrontal and association cortices

A

Medial division of the Spinothalamic tract

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25
Pain Matrix is made up of:
ACC (anterior cingulate) PFC Insular cortex Somatosensory cortex
26
Role of pain matrix (higher centers)
Imparting salience and valence of noiceptive stimuli
27
If pain signals tissue damage, why have endogenous analgesic mechanisms?
Central Mechanisms to suppress pain have significant survival value Stop the pain while you escape a dangerous situation
28
Endogenous mechanisms of analgesia need to have ____ so they don't inhibit pain's survival value
HIGH threshold of activation
29
Endogenous opioids
``` Met Enkephalin (delta), Leu Enkephalin, (delta ) Dynorphin, (kappa) Endorphin, (mu) Orphanin FQ (Nociceptin) (ORL1), Endomorphin 1 and 2 (mu) ```
30
Met Enkephalin receptor
delta opioid (DOR)
31
Leu Enkephalin receptor
delta opioid (DOR)
32
Dynorphin receptor
kappa opioid (KOR)
33
Endorphin receptor
mu (MOR)
34
Orphanin FQ/Nociceptin
ORL1
35
Endomorphin 1 and 2
mu (MOR)
36
Mechanism of opioid receptors (simple)
All opioid receptors are Gi/Go coupled
37
How opioid receptors work (complicated mechanism)
Inhibit adenyl cyclase --> decreased cAMP --> activate GIRK --> hyperpolarization --> N-type Ca channels close --> less NT release
38
Opioid receptors are (inhib or excit)
INHIBITORY (but effect depends on what type of cell they are on) Decreased Neurotransmission
39
Descending analgesic pathways (structure overview)
Amygdala --> PAG --> RVM --> spinal opioid interneurons | pathway held in check by tonic GABAergic inhibition in RVM and PAG
40
When GABA isn't on RVM and PAG
descending analgesic pathways can release endogenoys opioids to suppress pain transmission in the dorsal horn of the SC
41
Under normal physiological conditions the descending analgesic pathways are held in check by
tonic GABAergic inhibition on PAG and RVM
42
How to trigger analgesia in the descending analgesic pathway
electrical stim of PAG releases endogenous opioids --> these Opioids inhibit inhibitory neurons --> release the inhibition of the RVM and PAG (disinihbition) and allowing the release of endogenous opioids to suppress pain transmission = analgesia
43
Two cell types in RVM (rostral ventrolateral medulla)
'ON' cells = turned on by noxious stim --> pain | 'OFF' cells = turned off by noxious stim -->analgesia
44
'ON' cells are _____ by noxious stimuli and ____ by opioids; effect:
excited by noxious; inhibited by opioids | = turn off descending pathways and allow you to feel pain
45
'OFF' cells are _____ by noxious stimuli and ____ by opioids; effect:
inhibited by noxious; excited by opioids | = turn on descending analgesic pathways
46
How do opioids act at the spinal dorsal horn
opioids act presynaptically to inhibit Ca2+ channels and reduce glutamate release from C-fibres and A-delta fibers
47
Pathways of analgesia at the spinal cord via opioid interneurons
Descening pathways end on opioid interneuron --> opioid released onto presynaptic terminal of afferents --> inhibit Ca2+ channels (less Ca conductance) --> decreased NT release --> reduced EPSP
48
How opioids worrk on post-synaptic neurons
opioids act to incrrase K+ conductance in post-synaptic neuron --> hyperpolarized --> decreased NT release helps decrease firing
49
Mu receptors are found in the...
``` PAG RVM (rostral ventral medulla) Dorsal horn (substantia gelatinosa) VTA LC Pre-Botzinger region Enteric nervious system ```
50
Effects of Mu opioid receptors in the PAG, RVM, and dorsal horn
analgesia
51
Effects of Mu opioid receptors in the VTA
``` reinforcing effects (dopaminergic) ADDICTION ```
52
Effects of Mu opioid receptors in the LC
somatic effects of physical dependence | LC is an autnomic centre
53
Effects of Mu opioid receptors in the pre-botz region
respiratory depression | this area sets the resp. rhythmn
54
Effects of Mu opioid receptors in the enteric nervous system
constipation
55
Effects of opioids
* Morphine, Heroin, Fentanyl etc. * Analgesia * Euphoria * Sedation (Narcotic) * Respiratory depression * Constipation * Tolerance, dependence, ‘addiction’ * Hypotension * Pin point pupils (parasymp)
56
Opioid Interactions with the Immune system may explain
* Sweating and itching responses * Paradoxical hyperalgesia (more pain with inflammatory response) * Analgesic effect of naloxone
57
How can naloxone have Analgesic effects
At low doses has analgesic effect likely due to inhibition of opioid effects on the immune system
58
Drug addiction is:
* Continued use of drugs despite serious negative consequences * Compulsive drug seeking activity * Evidence of withdrawal when drug is unavailable (usually opposite of drug effect)
59
Behaviours can also be addictive because they are
Rewarding | Reinforcing
60
Rewarding effects can be (2 possibilities)
positive (e.g. euphoria) or relief of negative symptoms (e.g. pain, anxiety, depression)
61
Mesolimbic reward pathways
VTA --> NAc VTA --> basal forebrain/amygdala VTA --> medial PFC
62
Micking or potentiating DA in the mesolimbic DA pathway is...
rewarding and reinforcing
63
All potnetially addictive drugs produce _____ in animals
self administration
64
Importance of natural reinforcement
Dopaminergic reinforcement is important biologically --promotes activities that allow you to survive and reproduce (food, water, sex, warmth) AND drugs
65
Long-term drug treatment leads to
tolerance and dependence/withdrawal
66
Tolerance
need more drugs for same effect
67
Dependence
physiologicaly only normal when drug is in system
68
Animals will self stimulate _____ which activates reward pathway from ___. this is enhanced by ____.
Self stim medial forebrain bundle, activates VTA reward pathway effect enhanced by addictive drugs (amphetamines, opioids, cocaine, nicotine, PCP, benzodiazepines and ethanol)
69
Addicitve drugs increase ___ in the ___
DA in the NAc (as seen in microdialysis studies) | DA inhibits GABAergic spiny projection neurons in nucleus accumbens but how this relates to reward is unknown.
70
How cocaine creates reward
inhibits DA reuptake (more DA --> more inhibition of spiny neurons in NAc = reward)
71
How amphetamines create reward
reverse reuptake transporter to export DA and inhibits DA storage (so DA is pumped out not stored)
72
Cocaine and amphetamine _____ increase ___ transmission. Rewarding effects can be blocked by...
directly; DA | Rewarding effects blocked by DA antagonists or by the DA synthesis inhibitor a-methylparatyrosine
73
Opioid mechanism of reward
2 ways: disinhibition of VTA (inhibit gaba interneurons --> more DA release) Direct inhibition of spiny projection neurons in the NAc by DA (inhibition -> reward)
74
Nicotine reward
not generally behaviourally reinfocring | Directly stimulate VTA --> DA release --> DA inhibits NAc
75
Ketamine
effectively inhibit neurons in NAc Blocks NMDA receptors and excitatory glut drive to spiny projection neurons (when spiny projection neurons are inhibited = addiction)
76
'On' cell neuron type/NT type
GABAergic interneuron on cells are GABAergic interneurons excited by pain --> turn off descending pathway --> allow pain perception
77
'Off' cells function
pain/noxious stim --> inhibit OFF cell --> inhibit spinal inhibitory interneuron (disinhibition of pain)--> no analgesia therefore pain is felt opioids --> excite off cell (RVM neuron) --> stimulate spinal inhib interneuron --> inhibit pain (= analgesia)
78
descending analgesic pathway end on ______ which release _____ unto _____ terminals of _____ RESULT:
opioid interneurons, release opioids onto presynaptic terminals of afferents entering the SC resulting in decreased Ca conductance and therefore decreased NT release
79
Opioid modulation of K+
opioids directly interact with post-synaptic neurons in the SC --> increase K+ conductance --> hyperpol --> decrease NT release
80
DA ____ (inhibits/excites) ____ (neuron type) in NAc
inhibits GABAergic spiny projection neurons unsure how this relates to rewards
81
Increased DA onto the Nac -->
inhibition of NAc spiny projection neurons = reward
82
How increased DA creates reward
increased DA onto NAc --> da inhibits spiny projection neurons = addiction/reward

PMCOL 412 (35 decks)

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