Pain

Question 1

What are the 3 forms of pain?

Answer 1

nociceptive
inflammatory
pathalogical

Question 2

Where are nociceptors found?

Answer 2

primary sensory afferent neurons which require intense stimuli that are noxious
they are fist order neurons

Question 3

What is the definition of nociceptive pain?

Answer 3

an adaptive form of pain that serves as an early warning system to detect and minimise contact with damaging stimuli.
it is high threshold and usually activates A-d and c fibres

Question 4

How does nociceptive pain overide other activities of the NS?

Answer 4

initiates a withdrawal reflex

is very unpleasant and engages emotional components of the brain serving to provide avoidance in the future

Question 5

What is the definition of inflammatory pain?

Answer 5

it is adaptive and protective caused by the activation of the immune system due to infection or injury

Question 6

What is the result of inflammatory pain?

Answer 6

hypersensitivity and allodynia

Question 7

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

Answer 7

it discourages physical contact and movement

Question 8

What is the definition of pathological pan?

Answer 8

it is maladaptive with no protective function and arises from abnormal nervous system function

Question 9

What two forms of pathological pain exist?

Answer 9

neuropathic - from neural lesions which provides both positive (hypersensitivity) and negative (weakness) symptoms
dysfunctional - no neural damage or inflammation and only positive symptoms

Question 10

In what condition is there an absence of pain and how does it affect the body?

Answer 10

Congenital Insensitivity to Pain (CIP) where there is an absence of Na1.7 and therefore the individual cannot feel pain. This can result in excessive injury and infections and most likely a premature death.

Question 11

Which nociceptive receptors correspond to first and second pain?

Answer 11

A-delta fibres correspond to first pain which is the immediate withdrawl and stabbing pain
C-fibres correspond to second pain causing the throbbing and aching sensation

Question 12

What different types of A-delta and C fibres can initiate different pains?

Answer 12

A-HTM - a fibres requiring strong mechanical stimuli
A-MH a fibres requiring heat or mechanical stimuli
C-PM - c polymodal - usually superficial cutaneous stimuli
C-MH c machine heat have receptors in deep cutaneous tissue
C-HTM - high threshold mechanical but not noxious heat

Question 13

Where are nociceptors present?

Answer 13

everywhere except the brain with the exception of the meninges

Question 14

At what temperatures will A-delta an C fibres respond?

Answer 14

43C - Adelta type II and C

53C - Adelta type I

Question 15

What are the methods of neurotransmission between primary afferent and second order neurons in the dorsal horn pain pathway?

Answer 15

Glutamate is the Neurotransmitter exciting AMPA and NMDA receptors
Peptides such as substance P and CGRP causing a slow and prolonged EPSP and facilitate the action of the NMDA by removing Mg block

Question 16

What are the peptidergic polymodal nociceptors?

Answer 16

A subset of C fibres which are bi-directional and have both afferent and efferent functions: the AP can go to the dorsal horn but also other dendrites

Question 17

What are some of the pro-inflammatory mediators released at the peripheral terminus?

Answer 17

Efferent end: Substance P, CGRP

Afferent end: neurokinin A and Substance P

Question 18

What is hyperalgesia and allodynia?

Answer 18

primary hyperalgesia - extra sensitivity at the site of injury
secondary hyperalgesia - slight sensitivity due to leak of inflammatory mediators
allodynia - pain from a stimulus which would not normally evoke pain

Question 19

What does Substance P do at the site of inflammation/?

Answer 19

Causes vasodilation and extraversion of plasma proteins promoting the formation of bradykinin and prostaglandins
Releases histamine form mast cells
Sensitises the surrounding nociceptors

Question 20

What does CGRP do at the site of inflammation?

Answer 20

causes vasodilation

Question 21

What receptors may be found at the tissue damage site?

Answer 21

ASIC
P2X
TRP
K2P
GPCRs
RTK

Question 22

What is the function of NSAIDs?

Answer 22

to reduce pain by inhibiting the production of PGE, specifically PGE2

Question 23

What is the pathway for the production of PGE?

Answer 23

arachandonic acid -> cyclooxgenase 1/2(COX1/COX2) -> endoperoxides-> prostaglandin PGE2 or Prostacyclin PCI2

Question 24

Why are Coxibs important?

Answer 24

they serve to block the production of PGE2 which is activated by COX2 as COX1 is constituitively active

Question 25

What is the problem with taking NSAIDs for a while?

Answer 25

PGE2 helps preserve the stomach lining in response to acid so can cause stomach ulcers

Question 26

What is the problem with Coxibs?

Answer 26

they are prothrombotic

Question 27

What is the nociceptive pathway to the brain for A beta fibres?

Answer 27

show layers III,IV,V in the dorsal horn and innervate the wide dynamic range neuron
projects via spinothalamic, spinoreticular and spinomesencephalic tracts

Question 28

What is the pathway to the brain for the c and Adelta fibres?

Answer 28

tend to start in layers I and II and then project to the wide dynamic range neuron however the c fibre does this via an interneuron
Adelta and c fibres also connect with the nonciceptive specific neuron and project mostly from layers I and V

Question 29

How do the the descending pathways regulate spinal excitability?

Answer 29

serotonergic responses increase

noradrenergic responses decrease

Question 30

Where does the spinothalamic tract go?

Answer 30

starts in the contralateral side of the spinal cord and then rises through the medulla pons and into the thalamus where is projects to the primary sensory cortex

Question 31

Where does the spinoreticular tract go?

Answer 31

starts contra-laterally and then flows to the medulla and the reticular formation of the medulla and then to the pons and also forms a synapse at the reticular formation of the pons before travelling to the thalamus and the sensory cortex

Question 32

Where does the spinomesencephalic tract go?

Answer 32

only goes to the midbrain and not thalamus or cortex

Question 33

What is the gate control theory?

Answer 33

the idea of gate like control using interneurons. in this case the spinothalamic tract is innervated by Ab and c fibres and also an interneuron which sends inhibitory signals to the spinothalamic projection. the c-fibre will maximally stimulate the projection neuron while inhibiting the interneuron ensuring the maximum response occurs where the Ab fibres will stimulate the interneuron causing inhibition and smaller signals on the projection neuron. this is why by rubbing the painful area you stimulate the Ab fibres and the pain might feel less.

Question 34

How is the descending pathway from the brain regulated in pain?

Answer 34

several brain regions including the periventricular and peraqueductal grey (PAG) area may send signals down causing a profound analgesic effect when electrically stimulated. These PAG neurons project to the serotinergic raphe nuclei which in turn project down the dorsolateral white matter. This may stimulate an interneuron containing enkephalins which are the endogenous agonists of the opioid receptors