BB2 Revision7 Flashcards by patrick ellis

How can neuropathic pain occur due to C-fibre nociceptor pathway malfunctioning? [1]

Interneurons (lamina II) can spontaneously become active & fire pain

How well did you know this?

Not at all

Perfectly

Specifically, where do axons that transmit pain and form the spinothalamic tract decussate in the spinal cord? [1]

Anterior white commissure

How well did you know this?

Not at all

Perfectly

Label A

White anterior commissure

How well did you know this?

Not at all

Perfectly

Which of the folliwng numbers identify where the anterior and lateral spinothalamic tracts run in the spinal cord? [2]

5a: lateral spinothalamic tract
5b: anterior spinothalamic tract

How well did you know this?

Not at all

Perfectly

Transmission (Anterior Spinothalamic Tract)

Which fibres project within the Anterior STT?

Where does the Anterior STTT project to after travelling up the spinal cord / wheres the third order neurone? [1]

Ab, Ad and C fibres

Projects to ventral posterior lateral (VPL) and ventral posterior inferior (VPI) nucleus of the thalamus. (VPL/VPI) on the contralateral anterior STT tract

Third order neurones from VPL/VPI project to the somatosensory cortex (S1 and S2) - Provide exact localisation and physical intensity of noxious stimulus.

How well did you know this?

Not at all

Perfectly

Transmission (Lateral Spinothalamic Tract)

Which fibres project within the Lateral STT?

Describe its path

Ad and C fibres

Projects contralaterally via LSTT to mediodorsal nucleus of the thalamus (MDvc) and posterior thalamus (VPI and VMpo).

From mediodorsal nucleus of the thalamus (MDvc) innervates anterior cingulate cortex (ACC)

From posterior thalamus (VPI and VMpo) which innervates the rostral insula (unpleasant emotion of pain)

How well did you know this?

Not at all

Perfectly

Anterior STT: innervates the [] cortex via []

Lateral STT: innervates the [] & [] via the [] and []

Anterior STT
* Innervate the primary and secondary somatosensory cortex via VPL/VPI

Posterior STT:
* Innervates the anterior cingulate cortex and rostral insula via the mediodorsal nucleus of the thalamus (MDvc) and posterior thalamus (VPI and VMpo)

How well did you know this?

Not at all

Perfectly

Explain the mechansim of pain modulation at the dorsal horn via the Noradrenaline and serotonin neurons

Noradrenaline and serotonin neurons descend from locus coerulus and raphe nucleus respectively & exhibit excitatory repsonse on lamina II neurons

The lamina II neurons present here are inhibitory - so release GABA and ekephalins onto the INCOMING Aδ neurons, which reduces their activity

How well did you know this?

Not at all

Perfectly

The unpleasantness (painfull) character of pain is mediated via pain to which are the brain? [1]

Limbic systems

How well did you know this?

Not at all

Perfectly

Name three types of endogenous opoids and the receptors they can bind to [6]

Endogenous opoids:
* endorphins
* enkephalins
* dynorphins

Opoid receptors:
* Mu opioid receptor
* Delta opioid receptor
* Kappa opioid receptor

How well did you know this?

Not at all

Perfectly

How does binding of endogenous opiod to opiod receptor inhibit pain? [2]

Causes a decrease in Ca2+ release at pre-synaptic terminal

This inhibits release of glutamate and stops pain modulation

How well did you know this?

Not at all

Perfectly

How can you modulate pain via Abeta afferents? (e.g. if in pain - rubbing the area might help)

Ab afferent from skin also synapse excitably onto lamina II inhibitory cell body, that are used as interneurons from descending pain pathway (from noradrenaline and serotonin)

This causes more inhbitory GABA and enkephalins to be released on INCOMING Aδ neurons, which reduces their activity

How well did you know this?

Not at all

Perfectly

Chronic pain

What is allodynia and hyperalgesia?

Allodynia: a condition where pain is caused by a non-noxious (non-painful) stimulus (e.g. tickle with a feather).

Hyperalgesia: a condition where an abnormal increased pain sensitivity is caused by a noxious (painful) stimulus (e.g. hot water on sunburn).

How well did you know this?

Not at all

Perfectly

Chronic pain

Explain what causes peripheral sensitisation?

During injury (esp. inflammation), chemical mediators (i.e. cytokines, H+) can activate nociceptors and activate intracellular signalling mechanism, which can up regulate ion channels, thus increase membrane potential closer to depolarisation threshold.

This makes the sensory primary afferent fibres more sensitive to activation.

How well did you know this?

Not at all

Perfectly

Explain what causes central sensitisation

Continuous activation of the projection neurones can activate intracellular signalling mechanism, which can up regulate ion channels, thus increase membrane potential closer to depolarisation threshold.

This makes the projection neurones more sensitive to activation.

How well did you know this?

Not at all

Perfectly

Peripheral sensitisation

Explain what ectopic and ephatic activation of nocifibres are

In peripheral sensitisation:

Ectopic activation: spontaneous activation of fibres causing pain

Ephatic: lateral contact causes generation of AP on neighbouring fibre and cause pain

How well did you know this?

Not at all

Perfectly

Central sensitsation of pain

Explain what Abeta fibres collateral sprouting-induced pain is [1]

Abeta fibres (which dont normall cause paincan sprout in dorsal horn - which directly activates projection neurons which causes chronic pain

What is functional pain? [2]

no underlying lesion found despite investigation

pain is disproportionate to the degree of any clinically discernable tissue injury

Referred pain

Severe pain down a leg (sciatica) may be caused by a []

Hip problem may give rise to []

Gall bladder pain may be felt in the []

severe pain down a leg (sciatica) may be caused by a slipped disk in the back

a hip problem may give rise to knee pain

gall bladder pain may be felt in the right shoulder

[] & [] are the most common mental disorders associated with chronic pain.

What are the NTs that are involved in these mental disorders and how do the influence pain? [3]

Depression & anxiety are the most common mental disorders associated with chronic pain

Serotonin (5HT) & Norepinephrine (NE); generally suppress sensations of normal bodily functions

Dopamine (DA); modulates pain perception & dampens pain

Peripheral sensitization

How does Capsaicin reduce pain?

The relief of pain that may follow this topical treatment is thought to be related to the temporary deactivation of heat-sensitive epidermal nociceptors expressing the Transient Receptor Potential Vanilloid 1 (TRPV1)

Capsaicin excites pain and heat rececptors; but then desensitization the receptors and reduces pain

Explain the mechanism that causes peripheral sensitisation to pain

Primary afferent attracts substance P

Substance P attracts mast cells or neutrophils & releases histamines

Histamines, alongside other chemicals like prostaglandins, ATP, 5-HT, bradykinin

Substance P also dilates the blood vessels

This will excite the pain terminals

The nociceptor terminals become more sensitive to the same quantity of the chemical mediators.

What is the physiological effect of the molecule CGRP? [1]

CGRP is a highly potent vasodilator

Explain how Nav 1.7 sodium channel influences pain

When there is an injury, there is receptor potential in the primary afferent and if the potential is big enough it will create an action potential and pain (via Na & Ca2+ channels)

Nav 1.7 sodium channel is a threshold channel because it amplifies the receptor potential of DRG ganglions to reach the threshold for the Nav 1.8 channel found in DRG (which causes AP)

Describe the characteristics of primary erythromelalgia [2] What is the pathophysiology of behind primary erythromelalgia? [2]

Primary erythromelalgia is a rare **autosomal dominant** neuropathy characterized by the combination of **recurrent burning pain, warmth and redness of the extremities**. It is a channelopathy (genetic etiology) caused by **mutations of SCN9A,** the encoding gene of the voltage-gated sodium channel subtype **Nav1.7** - causes the channel to open with less depolarisation .

The difference between central and peripheral sensitization can be identified quite easily. How? [2]

The difference between central and peripheral sensitization can be identified quite easily, as **peripheral sensitization** becomes **heat**-**sensitive** whereas **central sensitization does not**

Explain the mechanism of how sensing pain in the face occurs

spinal **trigeminal nucleus** in the lateral medulla of the brainstem Incorporates sensory information principally from the three extracranial divisions of the **trigeminal nerve (V1, ophthalmic; V2, maxillary; V3, mandibular)** The SN projects both **contralaterally and ipsilaterally** to the ventral posteromedial nucleus of the **thalamus** (via the ventral and dorsal trigeminothalamic tracts) This sensory information will be relayed from the thalamus to the **primary motor cortex via the primary sensory cortex**, allowing response to stimuli of the face | (instead of the DRG, face uses trigeminal nucleus to conduct pain)

Which type of receptors is the midbrain periaqueductal gray full of? [1] Which nuclei does this receptor type influence? [4]

Opoid receptors - influences the: * parabrachial nucleus * medullary reticular formation * locus coerruleus * raphe nuceli

Describe the distribution of endocannabinoid receptors [3]

in the **pain pathway** at the **peripheral** and **central** (spinal and supraspinal) **levels** in areas of the brain and brainstem nuclei involved in nociceptive perception as **thalamus, amygdala, and periaqueductal grey matter**. Both CB1 and CB2 receptors have been detected in **non-neuronal cells participating in immune and inflammatory processes** in the **proximity** of the **primary afferent neurons nerve terminals.**

Explain the main function of the endocannabinoid receptors

Activate Via **retrograde transmission:** - Post synaptic neuron sends a message to pre-synaptic neuron to stop release of **GABA** and **glutamate** (e..g if GABA activated - will stop release of glutamate) E.g. Activation of GABA receptor causes release of endocannabinoid, which goes retrogradly (to the pre-synaptic terminal) and decrease release GABA)

What is important to consider about the symptoms of depression? [1]

symptoms may **present differently** in people with **different ethnic backgrounds** raising the issue of how best to assess depression cross-culturally for research purposes

Name a scale used to rate depression [1]

Hamilton Rating Scale for Depression

Which are the brain regions associated with depression? [6]

Amygdala Ventrolateral prefrontal cortex Dorsolateral prefrontal cortex Medial prefrontal cortex Striatal regions (ventral striatum) Hippocampus

Where is the subgenual anterior cingulate cortex ? [1] How is the subgenual anterior cingulate cortex effected during depression? [1] What structural implications does this have? [1]

Decreased metabolism: **significant reduction in glucose consumption** The **mean gray matter volume** of the **subgenual anterior cingulate cortex is reduced**

Describe a relationship between genetics and environments that causes depression: What occurs at a higher risk of major depression after significant life events? [1]

**5-HT transporter polymorphism** (impact on 5-HT signalling) is associated with a **higher risk** of **major depression after significant life events** The different alleles may lead to different levels of transcription of the transporter Therefore, the genetic variation modulates the response to stressful events

What is the DMD like in patients with depression? [2] In which particular areas? [2]

Major depression have an **increased functional connectivity within DMN** **increased** **connectivity** between **DMN and fronto-parietal** networks: **especially left subgenual cingulate area** involved in self-reference thoughts and negative recurrent thoughts = worse :(

# Neurotransmitter systems associated with mood disorders Which NT systems are implicated with depression? [2]

monoaminergic pathways: **noradrenergic** and **serotonergic** (but not the only players)

What happens to the hippocampus during stress in depression? [1]

Shrinks

Overview of changes to brain during depression [3]

* Decreased cortical thickness * Decreased mean grey matter in ACC due to decreased glucose metabolism * Volumes of hippocampal white matter decrease in patients with a first episode of depression

Between which two areas of the brain have a reduced connectivity in patients of depression who also **carry higher active MAO risk alleles?** [2]

**Amygdala–prefrontal** connectivity reduced may affect the course of major depression by disrupting cortico-limbic connectivity.

Describe interactions between key structures that involved in depression that cause an increase in **depressive ruminations**: Which areas of the brain become hyperactive? [4] Which areas of the brain become hypoactive

Hyperactive: * **amygdala** * **hippocampus** * **subgenual cingulate cortex** * **medial prefrontal cortex** Hypoactive: * **Dorsolateral prefrontal cortex** * **ventrolateral prefrontal cortex**