Somatosensory Function II: Pain

Question 1

Pain

Subjective experience

Answer 1

The subjective experience of pain is sculpted by psychological, social and biological factors.

Question 2

Pain Physiology

Answer 2

Many types of receptor provide many types of information, e.g. location, size and severity.

Question 3

Pain Purpose

Answer 3

To initiate an appropriate response

Question 4

Pain Definition

Answer 4

Unpleasant sensation in response to tissue damage.

Question 5

Pain Types

Answer 5

Acute and Chronic. Mechanical, chemical and thermal.

Question 6

Nociception

Answer 6

Nociception is the neural processes of encoding and processing noxious stimuli. Nociception refers to a signal arriving at the central nervous system as a result of the stimulation of specialised sensory receptors in the peripheral nervous system called nociceptors.

Question 7

Thermal pain:

Answer 7

• Triggered by extreme temperatures.
• TRP channels are involved in high noxious temperatures.
TRPV1 is activated at around 430C.
• TRPM8 channels are involved in low noxious heat.

Question 8

Mechanical pain:

Answer 8

• Triggered by mechanical stimuli that cause tissue damage.
• It is uncertain what channels are involved in mechanical pain but ASICs have been suggested to play a role in Aδ noxious mechanoreceptors.

Question 9

Chemical pain:

Answer 9

• Triggered by harmful chemicals.

* Capsaicin from chillies activates TRPV1 receptors

Question 10

Nociceptors: Threshold

Answer 10

Innocuous stimuli are coded differently than noxious stimuli.

1) Nociceptors possess a higher threshold for stimulation.
- Nociceptors have a higher activation threshold than non- nociceptive thermoreceptors
2) Nociceptorshaveanincreasingfiring rate in relation to intensity of heat.
- Nociceptors exhibit an increasing firing rate within noxious range whereas non-nociceptive thermoreceptors have a cap on their firing rate.

Question 11

Nociceptors: Summary

Answer 11

Nociceptiveneuronshavefreenerveendingsandthereceptor types expressed on their dendrites define the stimuli that they respond to.
• E.g.nociceptiveneuronsthatexpressTRPV1channelswillrespond to noxious heat.
• Manydifferentnociceptorscanbeononenociceptiveneuron allowing it to respond to a range of stimuli e.g. TRP receptors for various temperature ranges.
• Somenociceptorscanbecouplede.g.TRPV1hasbeenshownto act as a bradykinin-gated channel in response to B2 activation generating an influx of calcium.

Question 12

Nociceptive Fibres

Answer 12

Aδ fibers transmit information faster than C fibers and play a slightly different role because of this:
• Aδ fibres are first nociceptors and have small receptive fields on the skin which cause sharp localised pain.
• C fibres are secondary nociceptors and have large receptive fields which cause diffuse and long lasting dull aches.
Visceral nociceptors are also have large receptive fields and cause dull aches.

Question 13

Spinothalamic Tract

Answer 13

• Dorsal input enters via the dorsal root, synapses within the Dorsal horn (1st Order Neurone).
• Decussates, ascending via the Lateral spinothalamic tract (2nd Order Neurone).
• Synapses at the Thalamus before projecting to the sensory cortex (3rd Order Neurone).

Question 14

Spinal Cord Pain Circuit

Answer 14

• Nociceptive fibres enter the spinal cord through the dorsal horn.
• Synapse with interneurons within the Substantia Gelatinosa (Layer I) and Nucleus
Proprius (Layer II & III).
• Output via contralateral spinothalamic tract.

Question 15

Spinal Cord Pain Circuit: Gated Control

Answer 15

A mechanism to code the nociceptive component of sensory input.

• sensory afferents “gate” incoming information. This depends on the balance between these two inputs.
• sensory inputs converge on spinal neurons. Sensory information is transmitted to the forebrain.
• More recent experiments and have shown that the model is not correct in detail, however, this theory has transformed understanding of pain mechanisms.

Inhibitory neurons (yellow), found in the substantia gelatinosa (SG)
- Determine whether nociceptive (pain) input from the large or small diameter
fibre would be relayed through the spinal transmission system (red, T) to the higher CNS areas to consciously perceive pain.

Question 16

Ascending Pain signals travel from the spinal cord to the…

Answer 16

Thalamus and from the thalamus to the sematosensory cortex, the insula, the prefrontal cortex, the parabrachial nucleus and the peri aqueduct always grey.

Question 17

Descending pain signals travel from the ….. to the spinal cord

Answer 17

Frontal cortex, insula, hypothalamus, amygdala

Question 18

Neural Modulation of Pain Sensation

Answer 18

Negative emotional states alter pain-evoked cortical activation in brain regions and most consistently in the ACC.
Case study of mice that see cage mates in pain show increased pain behaviours.
EMPATHY
Simply observing another individual in pain activates pain-related brain regions.

Anticipation of pain relief activates descending pathways – primary contributor to placebo analgesia.
Imagining or anticipating a painful experience can lead to activation of pain pathways.

PRIMING

A patient with negative expectations may have a diminished response to pharmacotherapy

Question 19

As attention and emotion have opposing effects on pain perception and alter pain-evoked activation of different regions, this suggests

Answer 19

there are separate modulatory systems underlying their influence on pain.

a: Manipulating the attentional state primarily alters perceived pain intensity without significantly changing unpleasantness.
b: Altering the mood state alters perceived unpleasantness without changing the pain intensity.

IncreasednegativeemotionassociatedwithACC-fronto- PAG circuitry.
• Naloxone(mu-opioidantagonist)modulatespain- induced responsesinPAG/RVMandabolishesACC-PAG coupling – placebo analgesia pathways overlap with emotional modulation of pain pathways
• Attentional related alterations in pain-evoked activity in the insula correlated with SPL activity.
• Parts of the SPL have direct corticocortical projections to S1 / S2 and insula (attentional modulation of pain and descending pathways from IN to AMG - descending component?)

Question 20

Descending Control of the Spinal Cord Pain Circuit

Answer 20

Inhibitorypainmodulationatthespinalcordlevel
• Inhibitoryinterneuronsactivateduetotouch stimulus inhibiting nociceptor fibers presynaptically
• Gateclosed

Facilitatory or inhibitory
• PAG → Raphe nucleus (serotonergic); Locus coeruleus
(noradrenergic)
• Serotonergic modulation can be faciliatory or inhibitory depending on the receptor type
• Serotonin receptors in the dorsal root ganglion, afferent fibres as well as GABAergic interneurones