nociception and pain

Question 1

What are nociceptors?

Answer 1

nociceptors = free nerve endings (dendrites) of Ad & C fibres (sensory neurons)

Question 2

What stimulates the nociceptors?

Answer 2

intense mechanical, thermal or chemical stimuli

Question 3

Which types of afferent neurons are involved in fast pain and in slow pain?

Answer 3

FAST: A delta fibre free nerve endings
= intense mechanical or thermal timulus *threshold
Can precisely localised
SLOW:
C fibre free nerve endings
= intense mechanical, thermal or chemical stimulus
difficult to localise

Question 4

Where are the cell bodies of the 1st order neurons located?

Answer 4

Pain afferents synapse
in the dorsal horn:
- A delta fibres & C	fibres synapse	mostly in superficial	Rexed laminae (I &	II)
• Layer II	= substantia gelatinosa
= predominantly interneurons

Question 5

Name the two types of 2nd order neurons – where are their cell bodies located & from where do they receive input?

Answer 5

1. Nociceptive Specific (NS) neurons / Lamina I neurons:
   - respond exclusively to nociceptive afferents (A beta & C neurons)
2. Wide, Dynamic Range (WDR) neurons/ Lamina V neurons
   - receive input from Adelta & Ab fibres (& C fibres via dendrites or interneurons)
   - also receive visceral nociceptive input = convergence = 1 explanation for visceral nociception being referred to body surface (incorrectly attributes source)

Question 6

What are the precise locations of the synapses between 1st & 2nd order neurons? (laminae)

Answer 6

lamina V

Question 7

Name the 2 pain ‘systems’ and state the function of each.

Answer 7

FAST: 0.1 sec sharp
A delta fibre free nerve endings
= intense mechanical or thermal stimulus *threshold
Can precisely localised

SLOW: >/= 1 sec, aching, tissue destruction C fibre free nerve endings
= intense mechanical, thermal or chemical stimulus difficult to localise
INITIALLY BOTH ARE ACTIVATED SIMULTANEOUSLY

Question 8

SPINORETICULAR PATHWAY:

Answer 8

Reticular formation in brainstem:
• Output to dorsal horn, spinal cord ⇒modulation of pain
• Output to ventral horn, spinal cord ⇒motor response to pain
• Output to cortex, basal nuclei, cerebellum, thalamus, ⇒arousal, attention to stimuli

Question 9

Define ‘somatotopy’. How does it relate to pain?

Answer 9

point-for-point correspondence of an area of the body to a specific point on the central nervous system.
- neospinothalamic pathway: Organised
somatotopically and permits localisation of the source

Question 10

What is peripheral sensitisation? Explain the mechanism.

Answer 10

⇒ decreased threshold for activation of nociceptors
⇒ activation of previously inactive nociceptors
Results from repeated application of noxious stimuli
⇒ the release of chemicals in the area by the:
1. C fibres
• Substance P & CGRP
2. Damaged cells
• Bradykinin & Prostoglandin

Question 11

What is central sensitisation? Explain the mechanism.

Answer 11

a lowering of the threshold / increased sensitivity of the WDR 2nd order neuron
WDR firing rate is graded proportional to the amount of input from the C fibres
1. Severe or persistent injury
2. Increased C fibre discharge of CGRP & Substance P neurotransmitters
3. Decreases the threshold of the WDR neuron so that it fires more easily

• Decreases the threshold for the production of pain
• Can lead to spontaneous pain
• phantom limb pain – general anaesthesia + spinal +/ local anaesthesia

Question 12

What is pain modulation? Where can it occur

Answer 12

Aim is to decrease stimulation of the nociceptor
Aspirin & non-steroidal anti-inflammatories (NSAIDs)
block prostoglandin production

also at dorsal horn

Question 13

Explain ‘descending inhibition of pain’.

Answer 13

at dorsal horn
2. Descending inhibition /facilitation:
The	activity of the	2nd order neurons	(NS	& WDR) is affected by the sum of	inputs into the substantia gelatinosa (lamina	II) dorsal	horn
INPUTS:
• Abelta &C neurons
• descending	neurons from	PAG	& RF

Question 14

SPINOMESENCEPHALIC PATHWAY:

Answer 14

Periaqueductal gray:
• Output – descending fibresto dorsal horn ⇒modulation of pain
• Superior colliculus: ⇒reflex eye movements toward source of pain
• Mesencephalic reticular formation - amygdala – emotional aspects of pain

Question 15

SPINOHYPOTHALAMIC PATHWAY:

Answer 15

• hypothalamus controls neuroendocrine response to pain

- alpha and c fibres input

Question 16

PALEOSPINOTHALAMIC PATHWAY:

Answer 16

Dorsomedial & intralaminar nuclei, Thalamus
• project to cortical association areas including limbic ⇒ emotion & memory
* pain can be emotional
* autonomic response 2 pain: HR change, sweat