Module 1 - Readings

Question 1

Irimia et al. 2020 - Interictal amylin levels

Answer 1

• Investigated amylin and CGRP levels in CM and EM patients
• Interictal amylin levels increased in CM not EM while CGRP increased in both
• Possible that amylin is involved in the transition from EM to CM = biomarker potential
• Levels measured via immunosorbent assay
• Limitation = some were on prophylaxis, all were female

Question 2

Walker et al. 2015 - AMY1 receptor expression

Answer 2

• Looked at the expression of CGRPR and AMY1R in the trigeminal system
• Rats vs post-mortem human tissue
• found CGRPR and AMY1R was expressed in the trigeminal system in human tissue
• co-localisation of CTR and RAMP1 in the TG and brainstem
• Rat TG neurones had cAMP signalling when induced by rat CGRP and amylin
• used an array of assays
• no direct evidence for migraines

Question 3

Ghanzida et al. 2021 - Pramlintide

Answer 3

• treatment of pramlintide induced migraine-like attacks
• mainly acting via AMY1R
• Less significant arterial dilation and facial flushing than CGRP
• Consistent results in mice
• limitations = no placebo, almost all patients female, facial flushing hindered blinding

Question 4

Hendrikse et al. 2022 - CTR expression

Answer 4

• looked at the expression of CTR in the rodent brain in areas which are migraine relevant
• used CTR specific antibodies
• all antibodies detected CTR with significant immunoreactivity in the brainstem and midbrain = migraine relevant areas
• only looked at CTR expression in rodents
• not directly linked to migraines

Question 5

Aydin and Baykan 2025 - CGRP and Amylin in pediatric migraines

Answer 5

• Investigated differences in CGRP and amylin levels between pediatric migraine patients and control groups
• also looked at changes during attacks
• They found no significant variation between groups and within groups
• Possible that pediatric migraines behave differently than adult migraines
• Limitations = small sample size and some patients were receiving prophylactic treatment

Question 6

Rea et al. 2018 - CGRP inducing spontaneous pain in mice

Answer 6

• investigated if CGRP induces spontaneous pain in mice measured via the mouse grimace scale (MGS)
• CGRP administration causes an increase in MGS scores and squinting in light and dark conditions while antibodies significantly lowered the scores
• Spontaneous pain matches initial mild headache reported in humans

Question 7

Labastida-Ramirez et al. 2020 - Lasmiditan inhibits CGRP release

Answer 7

• investigated the modulation of trigeminal CGRP release by lasmiditan in rodents
• KCl-induced CGRP release was significantly inhibited in trigeminovascular components with lasmiditan and sumatriptan
• lasmiditan didnt have an effect in blocking artery dilation with CGRP suggesting it doesnt directly act on CGRP but instead suppresses CGRP release before it can go to other tissues
• lasmiditan had no vasoconstrictive effects = good for CV

Question 8

Miller et al. 2016 - CGRPR in primate trigeminovascular system

Answer 8

• compared humans vs monkeys
• in humans antibodies could bind in the neurones of the TG tissue whereas in monkeys binding occurred in the neurones and satellite glia cells of the TG
• both confirm expression in the trigeminovascular system
• highlights differential binding between species

Question 9

Ho et al. 2008 - efficacy of telcagepant

Answer 9

• Phase III clinical trial assessing telcagepant = CGRPR antagonist
• treatment groups saw significant pain relief and decrease in phonophobia/photophobia/nausea
• highlights the role CGRP plays in migraines

Question 10

Goadsby et al. 1990 - CGRP release during migraine

Answer 10

• CGRP was elevated in the cranial circulation but not in peripheral blood during a migraine headache
• more significant in those with aura than those without aura

Question 11

Eftekhari et al. 2010 - expression of CGRP and receptor components in the human TG

Answer 11

• CGRP, CLR and RAMP1 showed immunoreactivity in the TG but there was rarely colocalisation with CGRP and receptor components
• receptor components but not CGRP were detected in satellite glial cells
• Suggests possibility of CGRP signalling in the TG = migraines?

Question 12

Kaiser et al. 2012 - CGRP induced light aversion and rizatriptan treatment

Answer 12

• CGRP administration induced light aversion in mice = symptom of migraine
• rizatriptan reduced light aversion
• reveals CGRP role in light aversion = implicated in migraines

Question 13

Hansen et al. 2011 - CGRP doesnt cause migraines in FHP

Answer 13

• Administration of CGRP did not cause a significant difference in migraine-like attacks between FHP and controls
• suggests lack of sensitivity
• FHP behaves differently to other migraine classifications

Question 14

De Logu et al. 2019 - exogenous substances evoking periorbital allodynia in mice

Answer 14

• injected substances including CGRP, amylin and ADM pre-orbitally
• measured nociception via how long mice spent rubbing injected area or head shaking
• CGRP induced pain but amylin and ADM did not