Pain

Question 1

define pain

Answer 1

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

Question 2

name the 3 forms of pain

Answer 2

(i) Nociceptive (acute) pain (e.g. pin prick, visceral distension)
(ii) Inflammatory (prolonged) pain (e.g. sunburn, inflamed wound)
(iii) Pathological pain

Question 3

nociceptive pain begins with the activation of ………

Answer 3

nociceptors
-> specific peripheral primary sensory afferent neurons normally activated preferentially by intense stimuli

Question 4

name 3 types of intense stimuli?

Answer 4

thermal, mechanical, chemical

Question 5

what are the cell bodies associated with nociceptive pain pathway?

Answer 5

• dorsal root ganglia
• trigeminal ganglia

Question 6

what are nociceptors?

Answer 6

they are primary afferent neurons innervating peripheral tissues—activated only by mechanical, thermal, or chemical stimuli that are noxious. Comprise Aδ- and C-fibres. Transduction begins in free nerve endings—mediated by numerous receptors and channels.

they are first order neurons that relay information to second order neurons in CNS by chemical synaptic transmission

Question 7

nociceptive pain is ….. and ……

Answer 7

nociceptive pain is adaptive and is high threshold

• i.e. serves as an early warning system to minimise contact with damaging stimuli (noxious events) and provoked only by intense stimuli that activate nociceptors

Question 8

inflammatory pain is ……. and ……..

Answer 8

• inflammatory pain is adaptive and protective
  -> produces pain hypersensitivity

activates immune system in response to injury, or infection

assists in healing of a damaged body part

Question 9

define allodynia

Answer 9

pain in response to a nonnocipetive stimulus e.g. cold temperature or light stroke

Question 10

Nociceptive pain diagram

Answer 10

Question 11

Inflammatory pain diagram

Answer 11

Question 12

Pathological pain diagram

Answer 12

Question 13

what is the condition congenital insensitivity to pain? (CIP)

Answer 13

results due to loss of function mutations (missense, or in frame, deletions) in the gene SCN9A that encodes a particular voltage-activated Na+ channel (Nav1.7) that is highly expressed in nociceptive neurons

can result in:
- lip and tongue injury
- bruises and cuts
- multiple scars
- bone fractures
- joint deformity
- premature mortality

Question 14

what do meissner corpuscles respond to?

Answer 14

touch

Question 15

what do pacinian corpuscles respond to?

Answer 15

pressure

Question 16

what do ruffini endings respond to?

Answer 16

pressure

Question 17

what do the terminals of nociceptor neurons transduce a stimulus into?

Answer 17

electrical activity

-> stimulus (mechanical, thermal or chemical) opens cation-selective ion channels in nerve terminal to elicit a depolarising receptor potential

Question 18

what do low threshold units do?

Answer 18

respond to low intensity (non-damaging and non-painful)

-> LTM (low threshold mechanoreceptors): mediate touch, vibration and pressure

Question 19

what do high threshold unit do?

Answer 19

• nociceptors: respond to high (noxious, potentially damaging) but not normally low intensity stimuli

-> HTM’s also called mechanical nociceptors respond to high intensity mechanical stimuli

Question 20

what are thermal nociceptors?

Answer 20

• respond to extreme degrees of head >45 degrees or cold <10-15 degrees

Question 21

what are chemical nociceptors?

Answer 21

respond to substances in tissue (as found in inflammation) e.g. prostaglandins, bradykinin, serotonin, histamine, K+, H+ and ATP and many others.

Question 22

what are polymodal nociceptors?

Answer 22

respond to at least 2 of the above

Question 23

what are the 4 of the axons of the primary sensory afferents from skin

Answer 23

• Aα
• Aβ
• Aδ
• C

Question 24

what sensory receptor is Aα?

Answer 24

propioceptors of skeletl muscle
- thick myelination

Question 25

what sensory receptor is Aβ?

Answer 25

mechanoreceptors of skin

Question 26

what sensory receptor is Aδ?

Answer 26

pain, temperature - thinly myelinated, responds to fast pain (stabbing)

Question 27

what sensory receptor is C?

Answer 27

temperature, pain and itch (all noxious stimuli therefore are polymodal) - unmyelinated, responds to slow pain (burning, throbbing)

Question 28

what is the bodys natural response after tissue damage?

Answer 28

- peripheral sensitisation -> mediated by nociceptors at site of innjury/tissue inflammation -> causes hyperalgesia and allodynia

Question 29

what tracts are involved in the nociceptive pathway?

Answer 29

- spinothalamic and spinoreticulothalamic tracts

Question 30

describe nociceptive pathway?

Answer 30

- noxious stimuli stimulates a free nerve ending (either Aδ or C-polymodal) - first order neurone relays information to DRG or trigeminal ganglion and synapses at dorsal horn of spinal cord - second order neuron then relays this info to the brain (in anterolateral system e.g. STT, SR, SM tracts) info travels to thalamus (VP nucleus) and third order neurone passes information to somatosensory cortex (S1)

Question 31

what is STT tract involved in in pain?

Answer 31

Acts as a ‘warning system’ by signalling the exact location and severity of the injury and the duration of pain. Also analyses the features of the pain – is it burning, sharp, pricking, aching? - projection neurones originating from lamina 1 (fast fibre Aδ pain) and terminates in post nucleus of thalamus - signals from thalamus are relayed to somatosensory cortex by thalamocortical neurons

Question 32

what is the spinoreticular tract involved in in pain?

Answer 32

Registers the emotional/motivational component of pain, its inherent unpleasantness. - largely transmits slow C fibre pain (poorly localised) - signals to intralaminar nuclei of thalamus indirectly to brainstem (reticular formation) via reticulothalamic tracts - ends up in limbic area of forebrain (cingulate and insular cortices)

Question 33

what is the spinomesenchepalic tract involved in in pain?

Answer 33

This pathway is therefore involved in the modulation of pain, and the emotional component of pain. - also involved in control and inhibition of pain!!! - afferents of this tract terminate in periaqueductal grey matter (PAG), and misbrain raphe nuclei. - both of which give rise to descending fibres that modulate nociceptive transmission - therefore when PAG is stimulated can activate a natural pain suppression system which involves the release of endogenous opiods

Question 34

name 3 analgesics in order of weakest to strongest in terms of clinical efficacy

Answer 34

- NSAID (aspirin, diclofenac, ibroprofen) - Weak opioid (codeine, tramadol) - Strong opioid (morphine, heroin, fentanyl) -> combinations of 1+2 or 1+3 are used in mod/severe pain

Question 35

what is an opiod?

Answer 35

- any agent (inc endogenous peptides,(endorphins/enkephalins) that act upon opioid receptors

Question 36

what is an opiate?

Answer 36

- substance extracted from opium

Question 37

how do NSAIDs act?

Answer 37

act to reduce nociceptor sensitization - inhibit synthesis and accumulation of prostaglandins by COX enzymes (COX-1 and COX-2)

Question 38

what is the descending supraspinal projections?

Answer 38

- pathway beginning at PAG (gray matter in midbrain) which relays inomayion to RVM. then travel down spinal cord and activate endogenous opiate system to suppress pain

Question 39

how do opioids work?

Answer 39

- bind to opioid receptors (usually μ-receptors (G protein-coupled receptor)). - small proteins/peptides named enkephalins are the endogenous agonists of opioid receptors. -

Question 40

cellularly how do opioiods work?

Answer 40

- inhibit opening of voltage-activated Ca2+ channels (suppressing presynaptic excitatory NT release) - opening of K+ channels (suppresses post-synaptic excitation of projection neurones)

Question 41

where is PAG found?

Answer 41

in the midbrain surrounding the cerebral aqueduct

Question 42

what else does the PAG do?

Answer 42

- regulates HR and BP - autonomic processes (bladder control and contraction) - fearful and defensive reactions - production of vocalizations best known for its role in analgesia