Final prep

Question 1

What Nav1.3 study indicated that it was involved in pain generation?

Answer 1

Hains and colleagues,2004 -> antisense knockdown of NaV1.3 expression attenuated pain-related behaviour associated with both spinal cord injury and chronic constriction injury.

Question 2

What does low does TTX show?

Answer 2

inhibits thermal and mechanical hypersensitivity in a chemotherapy-induced neuropathic pain model

Question 3

What did Fertleman find in PEPD?

Answer 3

Eight distinct mutations in NaV1.7

three of these mutations shows attenuation of fast inactivation of NaV1.7 resulting in persistent sodium currents

Question 4

What are the implications of Fertleman’s findings?

Answer 4

• Deficit in inactivation may promote a prolonged action potential and repetitive firing in response to a stimulus

Question 5

What did Yeoman’s show with siRINA knockdown of Nav1.7 encoded by a viral vector?

Answer 5

attenuates inflammatory hyperalgesia

Question 6

What does faster re-priming of Nav1.8 indicate?

Answer 6

likely to contribute to continuous firing activity during sustained depolarisations

Question 7

What did Joshi show with knockdown of Nav1.8?

Answer 7

antisense oligonucleotides attenuate the development and maintenance of neuropathic pain (Joshi et al., 2006)

Question 8

What does siRNA knockdown of Nav1.8 show?

Answer 8

siRNA selective knockdown of NaV1.8 reverses mechanical allodynia (Dong et al.,2007)

Question 9

What did Ostman 2008 show?

Answer 9

Nav1.9 underlies the TTX-R persistent current present in sensory neurons

Question 10

What does activation of PKC pathways do?

Answer 10

potentiates NaV1.9-like currents in sensory neurons

Question 11

What did Martinez and Melgar show?

Answer 11

NaV1.9 knockout mice also show a reduction in the development of visceral mechanical hypersensitivity associated with acute inflammation compared with wild type mice

Question 12

Moyer’s 2 compounds

Answer 12

AM-8145 and AM-0422

Question 13

Early Nav1.8 blocker

Answer 13

A-803467

Question 14

What did Oddiah and Woolf show about NGF?

Answer 14

concentration of NGF in the skin increases in response to inflammation

Question 15

What did Svennson find after injecting NGF into the masseter muscle?

Answer 15

local mechanical allodynia and hyperalgesia

Question 16

What did Kawamoto show about NGF and mast cells?

Answer 16

Exposure of isolated mast cells to NGF -> 5-HT

Question 17

What did blocking NGF show in Zahn’s model of post-operative pain?

Answer 17

reduces thermal hypersensitivity and resting pain

Question 18

What do peptibodies consist of?

Answer 18

fusion proteins composed of the heavy chains of IgG and peptides that bind to NGF

Question 19

Who showed that NSAIDS caused gastric ulcers?

Answer 19

Peskar, 2001

Question 20

Who showed that COX 2 inhibitors caused heart problems?

Answer 20

Solomon, 2005

Question 21

Who showed that the efficacy of Tapentadol could be predicted by CPM?

Answer 21

Niesters, 2014

Question 22

What studies were done in monkeys and humans to show that hyperalgesia spreads beyond peirpheral sensitizaiton?

Answer 22

noxious mechanical and chemical stimuli produce extensive spreading hyperalgesia without producing the same degree of spreading sensitization of primary afferent nociceptors in monkeys (Campbell et al. 1988) or humans (LaMotte et al. 1992).

Question 23

Who showed that the dorsal horn expands its receptive field to incorporate a site of injury?

Answer 23

McMahon and Wall, 1984

Question 24

Who used imaging to show topographical changes in PLP patients?

Answer 24

Karl et al.,2001

Question 25

Which regions in CBP show reduced grey matter density? and who showed this?

Answer 25

somatosensory cortex, PFC, thalamus and brainstem in comparison to control (Schmidt-Wilcke et al., 2006)(Apkarian et al., 2009)

Question 26

Which regions in fibromyalgia show reduced grey matter density? and who showed this?

Answer 26

medial PFC, anterior cingulate cortex (ACC), insular cortex, amygdala and parahippocampal gyri

Schmidt-Wilcke et al., 2007

Question 27

Why would early injury affect pacemaker neurons?

Answer 27

pacemaker activity is highly responsive to sensory experience

Question 28

What are tactile and noxious inputs targeted to in the neonatal cord?

Answer 28

Targeted to low-threshold

Targeted to high-threshold

Question 29

How many rodent postnatal weeks for descending inhibition to develop and who showed this?

Answer 29

4

Hathaway 2009

Question 30

How does glycinergic inhibitory maturation occur?

Answer 30

Activity, in terms of sensory influence from the physical environment, provides tactile and noxious input in postnatal life and drives the maturation of high-threshold connectivity and synaptic transmission in the dorsal horn (in addition to endogenous pacemaker activity), which, in turn, drives glycinergic inhibitory maturation

Question 31

What are the implications of early injury?

Answer 31

endogenous spinal inhibitory tone is reduced and less effective

balance of descending facilitation and inhibition may be disrupted

Question 32

What did changes in amygdala volume correlate with?

Answer 32

degree and directionality of thermal sensitivity

Question 33

What does neonatal hindpaw inflammation do to adult supraspinal circuitry and who showed this?

Answer 33

long-term alterations in supraspinal circuitry and enhanced inhibition from the RVM (Zhang et al.,2010)

Question 34

What does neonatal hindpaw inflammation do to adult PAG and who showed this?

Answer 34

alterations in opioid- mediated responses in the periaqueductal grey (Laprairie and Murphy, 2009)

Question 35

What did minocycline prevent?

Answer 35

prevent persistent mechanical and thermal hyperalgesia following secondary incision in adult male rats