Background: Migraine is a common disease with a global prevalence of about 15%. Migraine is divided into two main types; migraine with aura or migraine without aura. Migraine symptoms include moderate or severe unilateral pulsating pain exacerbated by physical activity, nausea and vomiting as well as light and sound sensitivity. Headaches lasting ≥ 15 days per month of which ≥ 8 of the days are migraine are defined as chronic migraine. Episodic migraine is defined as less than 15 headache days per month. The full reasons for how and why migraine arises are not yet fully understood. The main hypothesis is that migraine is due to a hypersensitivity in the brain that involves activating and sensitizing the trigeminovascular system. Calcitonine-related peptide (CGRP) has been shown to be an important neurotransmitter in the pathophysiology of migraine that mediates pain through vasodilation of intracranial vessels and an increased sensitivity of A-δ fibers. New drugs in the form of monoclonal antibodies directed against CGRP or the CGRP receptor have been developed to try to stop the CGRP signaling. Currently, there are four approved drugs: galcanezumab, fermanezumab and eptinezumab, which are three monoclonal antibodies directed against CGRP and erenumab which is a monoclonal antibody directed against the CGRP receptor. Purpose: The purpose of this literature study was to investigate how effective treatment with the monoclonal antibodies erenumab, fremanezumab, galcanezumab and eptinezumab directed against CGRP or the CGRP receptor is as prophylaxis against episodic and chronic migraine versus placebo. Method: A literature study was performed by reviewing articles retrieved from the Pubmed database. A free text search was done in Pubmed with the keywords "fremanezumab" OR "eptinezumab" OR "galcanezumab" OR "erenumab". The studies should be randomized, double-blind and placebo-controlled with the aim of investigating the efficacy and tolerability of treatment with erenumab, fremanezumab, galcanezumab or erenumab. A total of eight studies were selected for review. Results: Two studies reviewed erenumab, three studies reviewed fremanezumab, two studies reviewed galcanezumab and one study reviewed eptinezumab. The results showed that all four substances significantly reduced the number of migraine days per month compared to placebo with a mean change of −2.1. Number needed to treat (NNT) to produce ≥ 50 % reduction in migraine frequency varied between 4 – 33 in the eight studies. Conclusion: The results of the eight studies showed that treatment with erenumab, fremanezumab, galcanezumab or eptinezumab in patients with chronic and episodic migraine significantly reduce the number of migraine days per month compared to placebo. The treatments have been well tolerated and there have been relatively few side effects that have been comparable to placebo. However, more long-term studies need to be done to detect any long-term side effects.

This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.

This study investigated the role of opioid, adenosine, bradykinin, and calcitonin-gene related peptide (CGRP) receptors, and potential ‘cross-talk’ among suspected G-protein coupled receptors in a humoral model of remote ischemic preconditioning (rIPC) cardioprotection. Compared to Control dialysate (from non-preconditioned donor rabbit blood), rIPC dialysate (from remotely preconditioned blood) reduced cell death in rabbit cardiomyocytes following simulated ischemia and reperfusion. Non-selective, δ-, or κ-opioid receptor blockade and non-selective adenosine receptor blockade abolished rIPC dialysate protection; whereas, bradykinin B2 and CGRP receptor blockade had no effect. Non-selective adenosine receptor blockade fully and partially abolished protection by κ- and δ-opioid receptors, respectively. Multiple reaction monitoring mass spectrometry detected low levels of adenosine, and other preconditioning substances, in the dialysate. An increase in extracellular adenosine was not detected during opioid-induced preconditioning to explain this cross-talk. These results suggest that δ-opioid, κ-opioid, adenosine receptors, and opioid-adenosine cross-talk are involved in rIPC of freshly isolated cardiomyocytes.