An introduction to pain

Question 1

What is pain?

Answer 1

An unpleasant sensory and emotional experience, associated with actual tissue damage to described in terms of such damage

Question 2

What are the three forms of pain?

Answer 2

Nocioceptive-adaptive
Inflammatory-adaptive
Patholgical-maladaptive

Question 3

What is a nociceptor?

Answer 3

Specific peripheral primary sensory afferent neurones normally activated by intense noxious stimuli(mechanical, thermal or chemical)- they relay information to second order neurones in the CNS by chemical synaptic transmission

Question 4

What is congenital insensitivity to pain (CIP) and what may occur?

Answer 4

A very rare condition due to loss of function mutations in a gene that encoded voltage-activated Na+ channel that is highly expressed in nociceptive neurones

May have lip and joint injury, bruises and cute, multiple scare, bone fractures, joint deformity and premature mortality due to multiple injuries

Question 5

Subtypes of nociceptor

Answer 5

Aδ- and C-fibres

Aδ- –> mechanical/thermal nocioceptors,thinly myelinated. Medaite first or fast pain

C-fibres –> Unmyelinated, collectively respond to all noxious stimuli. Mediate second or slow pain

Question 6

First and second pain

Answer 6

First pain- e.g. lancing, stabbing,prickling sensation

Second pain- e.g. burning, throbbing,cramping,aching sensation

Question 7

Peptidergic C-fibres have both afferent and efferent functions T/F

Answer 7

T

Afferent- transmit nociceptive information to the CNS via release of glutamate and peptides (substance P,neurokinin A) within the dorsal horn

Efferent- release pro-inflammatory mediators e.g. calcitonin gene-related peptide (CGRP),substance P from peripheral terminals. Contributes to neurogenic inflammation

Question 8

Define hyperalgesia

Answer 8

Heightened sensitivity to noxious stimuli.

Question 9

Describe the development of neurogenic stimulation

Answer 9

Free nerve ending

Axon of nociceptor (first order neuronese)

Soma within dorsal(posterior) root ganglion

Dorsal (posterior) horn of spinal cord

axon of projection (second order) neurone

Spinothalmic and spinoreticulothalamic tracts

Question 10

What is inflammatory pain caused by?

Answer 10

Activation of the immune system in injury or infection.

Question 11

How does inflammatory pain assist with the healing of a damaged body part?

Answer 11

discourages physical contact and movement

(However although adaptive nonetheless required reduction in ongoing inflammation (e.g. rheumatoid arthritis) to alleviate suffering

Question 12

What are the two types of pathological pain?

Answer 12

neuropathic-neural lesion, pos and neg symptoms

dysfunctional- no neural lesion, no inflammation, positive symptoms

Question 13

What receptor is particularly activated by noxious heat

Answer 13

TRVP1- greatly sensitised in inflammation to become active at body temperature

Question 14

What ion channels does H+ activate

Answer 14

acid sensing ion channels (ASIC)

Question 15

What receptors does ATP activate?

Answer 15

P2X and P2Y

Question 16

What receptors does bradykinin activate?

Answer 16

B2

Question 17

In the long term what does noxious stimulation increase

Answer 17

spinal excitability contributing to hyperalgesia and allodynia

Question 18

Brief outline of neurogenic inflammation

Answer 18

• Peptides (SP and CGRP) released from free nerve ending of peptidergic nociceptor due to tissue damage, or inflammatory mediators
• SP causes vasodilation and extravasation of plasma proteins (promotes formation of bradykinin and prostaglandins), release histamine from mast cells and sensitises surrounding nociceptors
• CRGP induces vasodilation
• Primary and secondary hyperalgesia and allodynia ensue

Question 19

What is the chain of events in neurotransmission between the primary afferent and second order neurone in the dorsal horn

Answer 19

Action Potential

Opening of voltage-gated Ca2+ channels

Ca2+ influx

Glutamate release

Activation of glutamate receptors

Membrane depolarisation

opening of voltage-gated Na+ channels

Action Potential

Question 20

What is the primary transmitter in the neurotransmission between the primary afferent and second order neurone in the dorsal horn?

Answer 20

Glutamate - fast e.p.s.p and neuronal excitation

(peptides- substance P and CGRP also participate particularly during high frequency stimulation causing a slow and prolonged e.p.s.p

Question 21

Where are primary afferent cell bodies located?

Answer 21

Dorsal root ganglia

The axons terminate centrally in the dorsal horn of the spinal cord in various laminae of Rexed

Question 22

Cells that receive input from only Ab-fibres are ______

Answer 22

Proprioceptive

Question 23

Wide dynamic range (WDR) neurones receive input from…

Answer 23

all three types of fibre ( C- and Aδ and Aβ) and thus respond to a wide range of stimuli

Question 24

Second order neurones ascend the spinal cord in the anterolateral system comprising mainly…

Answer 24

• The spinothalamic tract (STT)

- The spinoreticular tract(SRT)

Question 25

What projection neurones are involved in the STT?

Answer 25

STT
-Fast fibre Aδ pain. Originate lamina I, terminate in posterior nucleus of thalamus
-WDR neurones. Originate lamina V, terminate in posterior and ventroposterior nucleus of the thalamus
Pain perception required simultaneous firing in both pathways

Question 26

What in involved in the SRT

Answer 26

SRT

• slow C-fibre pain
• makes extensive connections with reticular nuclei in the brainstem
• Involved in autonomic response to pain, arousal, emotional responses, fear of pain