L14 Sensory Processing and Pain

Question 1

Describe the divisions of the peripheral nervous system.

Answer 1

PNS divides into afferent (sensory) NS and efferent (motor) NS.
Motor NS further divided into somatic nervous system and autonomic nervous system.
Autonomic NS divided into sympathetic, parasympathetic and enteric.

Question 2

How many segmental spinal nerves are there?

Answer 2

30 pairs.

Question 3

What is the origin of the segmental spinal nerves?

Answer 3

Form from the coaleescence of the dorsal and ventral roots of the spinal cord.

Question 4

Where are most of the pain sensing neurons found?

Answer 4

In the dorsal root ganglia.

Peripheral axons of DRG project to the skin, viscera and muscle.

Question 5

Which plexus innervates the arms?

Answer 5

Brachial plexus (C3-T2)

Question 6

When plexus innervates the legs?

Answer 6

Lumbosacral plexus (L3-S4)

Question 7

What are the 3 major functional sub-classes of adult DRG neurons?

Answer 7

• Proprioceptive neurons
• Low threshold mechanoreceptors
• Temperature, itch responsive and nociceptive neurons

Question 8

Describe proprioceptive neurons.

Answer 8

• Very large cell bodies
• Large calibre, heavily myelinated axons
• Terminate in the intermediate zone and ventral horn in spinal cord
• Peripheral axons innervate skeletal muscles, joint capsules, Golgi tendon organs
• Provide spatial awareness of limbs

Question 9

Describe low threshold mechanoreceptors.

Answer 9

• Medium to large cell bodies
• Heavily myelinated
• Terminate deep in the dorsal horn of the spinal cord
• Peripheral axons innervate specialised end organs e.g. hair follicles, Ruffini endings, Pacinian corpuscles
• Function is to detect light touch, vibration, surface texture etc (tactile senses)

Question 10

Describe temperature, itch responsive and nociceptive neurons.

Answer 10

• Mainly small cell bodies
• Either not myelinated axons (called c-fibres) or lightly myelinated (called A𝛿-fibres)
• Nociceptive = pain transmitting
• Terminate in superficial dorsal horn region
• Axons branch profusely and terminate as naked nerve endings in the dermis of the skin, naked endings contain variety of ion channels and receptors which detect noxious stimuli
• Function is to detect painful stimuli, temperature and itch

Question 11

What are the 3 main ascending fibre tracts which carry nociceptive signals to the brain and where are they found?

Answer 11

Ascending fibre tracts, all found in the anterolateral region of the spinal cord.

• Spinothalamic tract (direct anterolateral pathway)
• Spinoreticular tract (indirect anterolateral pathway)
• Spinomesencephalic tract (indirect anterolateral pathway)

Question 12

Describe the spinothalamic tract.

Answer 12

• The nociceptive neurons (axons composed of C-fibres or A𝛿-fibres) synpase with projection neurons found in laminas I and V of the doral horn in the spinal cord
• The axons cross the midline, travel up spinal cord through the medulla, pons and terminate in the thalamus
• Make synaptic connection with a thalamic neuron (either in the ventral posterior lateral nuclei or ventral posterior inferior nuclei)

Question 13

Is pain received via the spinothalamic tract localised or not?

Answer 13

Yes, the pain is localised and precise because the thalamus is somatotopically mapped.

Question 14

Describe the spinoreticular tract.

Answer 14

• C-fibre nociceptive neurons make indirect contact with projection neurons in laminas I and V through excitatory interneurons found in laminas II and III
• Long axons cross the midline, travel up through medulla and pons
• Makes synaptic connections with neurons in the reticular formation
• Neurons in the reticular formation project to neurons in the intralaminar nuclei of the thalamus

Question 15

Is pain recieved via the spinoreticular tract localised or not?

Answer 15

No, the pain is dull, persistent and poorly localised.

Question 16

What is the purpose of the spinoreticular tract?

Answer 16

• Carries info on dull, persistent and poorly localised pain
• Produces arousal response allowing us to engage the fight or flight response in reaction to the nociceptive input

Question 17

Describe the spinomesencephalic tract.

Answer 17

• C-fibre nociceptors make indirect contact with dorsal horn projection neurons via excitatory lamina II interneurons
• Axons cross midline, travel up anterior lateral pathway, make synpatic connections with neurons in the parabrachial nucleus
• Neurons in the nucleus project to the hypothalamus, amygdala and cingulate cortex
• Neurons continue up to the periaqueductal gray (PAG) which controls descending pain modulation

Question 18

What is the purpose of the spinomesencephalic tract?

Answer 18

• Engages with autonomic nervous system, allowing response form system to stimuli
• Creates emotional response to painful stimuli
• Provides input to centres within the brain (PAG) which control the descending modulation of pain

Question 19

What is the benefit of pain?

Answer 19

A protective mechanism to minimise tissue damage and aid survival.

Question 20

What is pathological pain?

Answer 20

• Persistent pain
• Prolonged hyperalgesia caused by central sensitisation of the projection interneuron and/or the peripheral sensitisation of the primary nociceptor, causes debilitating persistent pain
• E.g. osteoarthritis, interstitial cystitis, pancreatitis
• Nerve damage can lead to prolonged, severe neuropathic pain that does not respond to analgesics

Question 21

What is the spinal pain reflex?

Answer 21

• Reflex which induces automatic response to pain
• A𝛿 nociceptive neurons detect stimuli, e.g. extreme heat, sends AP to dorsal horn
• Synaptic connection with excitatory interneuron in the dorsal horn
• Interneuron projects to motor neurons in the ventral horn
• Motor neurons innervate hand and arm muscles, to move the hand away from the heat source

Question 22

How is temperature percieved?

Answer 22

• Ion channels in temperature responsive and nociceptive neurons change conformation and open when temperature changes
• This allows sodium and calcium ions to pass through, causes depolarisation, creates AP

Question 23

What are the 6 main temperature detecting ion channels?

Answer 23

Main heat detecting ion channels:

• TrpV4
• TrpV3
• TrpV1
• TrpV2

Main cold detecting ion channels:

• TrpM8
• TrpA1

Question 24

Describe the chemical changes that occur in response to skin damage.

Answer 24

1) Skin is cut, dead and dying cells release potassium and hydorgen ions, and ATP
2) Potassium directly depolarises nociceptor terminals
3) Hydrogen depolarises nociceptors by activating acid sensing ion channels
4) ATP binds to P2X3 ion channels on nociceptor terminals causing depolarisation

Question 25

Describe the response of enzymes to skin damage.

Answer 25

1) Cyclo-oxeygenase enzymes make prostaglandins from lipid membranes e.g. PGE2
2) Bradykinin is generated from kininogen
3) PGE2 increases the sensitivity of nociceptors to other painful stimuli
4) Bradykinin binds to a specific GPCR on nociceptive neurons to depolarise them and also sensitises TrpV channels

These enzymes cause hyperalgesia (heightened response to painful stimuli).

Question 26

What is substance P?

Answer 26

• A neuropeptide which diffuses into the skin when nociceptor axon terminals depolarise
• Increases capillary blood flow
• Causes fenestrations leading to localised oedema
• Induces mast cells to degranulate, empty their contents into ECF e.g. histamine, prostaglandins, bradykinin
• Sensitises nociceptors to be activated by lower intensities of noxious stimuli

Question 27

Describe the role of nerve growth factor in peripheral sensitisation.

Answer 27

• NGF is released when tissues are damaged
• NGF binds to receptros on nociceptive nerve neuron endings and phosphorylates TrpV1
• Enhances sensitivity of nociceptive neurons to noxious stimuli
• Increases degranulation of mast cells, and increases expression of acid sensing ion channels, substance P etc.

Question 28

Describe the role of nerve growth factor in central sensitisation.

Answer 28

• NGF promotes synthesis of brain derived neurotrophic factor, and its release from the central terminalis in the dotsal horn
• NGF upregulates substance P expression
• BDNF and subP promote long term potentiation at the DRG neuron/projection neuron synapse making projection neurons more sensitive to nociceptive input
• Overall induces a state of hyperalgesia

Question 29

What are the 3 in-built mechanisms for regulating the intensity of pain perception?

Answer 29

• Pain gating in the dorsal horn
• Serotonergic and noradrenergic descending control
• Endogenous opioids

Question 30

What is pain gating in the dorsal horn?

Answer 30

1) AP along nociceptor axon induces release of glutamate
2) Acitvity-induced glutamate depolarises an interneuron causing the AP to be sent to the thalamus
3) Low threshold mechanoreceptors (LTMs) branch in the dorsal horn and synapse with local inhibitory interneurons
4) Activity in LTMs causes the release of the inhibitory neurotransmitter GABA (presynaptic inhibition)
5) LTM branches also synapse with inhibitory interneurons making synaptic contact with projection interneurons (postsynaptic inhibition)

Question 31

What is serotonergic descending control?

Answer 31

• Pathway originates in the nucleus raphe magnus
• Seretonergic raphe neurons project to the dorsal horn
• Either synapse with DRG neuron terminals, local interneurons or projection neurons
• Descending raphe neurons either inhibit or facilitate nociceptive transmission in the dorsal horn, dependent on the serotonin receptor type

Question 32

What is noradrenergic descending control?

Answer 32

• Noradrenergic neurons project to dorsal horn
• Either synapse with DRG neuron terminals, local interneurons or projection neurons
• Always inhibit nocicpetive transmission in the dorsal horn

Question 33

What are endogenous opioids?

Answer 33

• Small peptides produced by cells in the hypothalamus and pituitary gland in response to physical exertion, pain, excitement and sexual pleasure
• Have analgesic effects
• E.g. endorphins, met enkephalin, dynorphins A and B, nociceptin