The relationship of nociceptine and anandamide levels in migraine withattack frequency and analgesic over use

Background: The aim of this study is to show whether the levels of anandamide and nociceptine change with chronicity of pain and their relationship with analgesic overuse. According to our hypothesis, since anandamide and nociceptine are peptides with analgesic effects; plasma levels are expected to be lower in chronic migraine compared to episodic migraine and to be lower in those with excessive use of analgesics compared to those who do not. Methods: In our study, 29 patients diagnosed with Episodic Migraine without Aura, 15 patients diagnosed with Chronic Migraine without Drug Overuse, 16 patients diagnosed with Drug Overuse Headache according to the International Classification of Headache Disorders 3 Beta diagnostic criteria were included. 31 volunteers without any illness or headache were included for the healthy control group. All patients and volunteers were selected from Akdeniz University Hospital Neurology and Emergency Clinics. For groups, forms including diagnostic criteria, demographic features and exclusion criteria were filled and all data were recorded. In all three patient groups, all patients were asked to keep Akdeniz University Neurology Department Headache Diary for one month. Migraine Disability Assessment (MIDAS) and Beck Depression Scale (BECK-D) were applied for all patient groups. After keeping Akdeniz University Neurology Department Headache Diary for one month, blood samples were taken between 8-11 a.m. from patients who did not have headache attacks and did not use analgesics in the last 72 hours. Venous blood samples taken into gel biochemistry tubes (Becton Dickinson and Company, New Jersey, United States) were centrifuged at 4000 rpm at +4°C for 4 minutes; serums were separated and stored at -80°C until analysis. Results: No statistically significant difference was found between migraine groups and the control group in terms of mean values of nociceptine. Looking at the median values of nociceptine (ng / L), the highest median value was seen in the Chronic Migraine group with 235.76 (7.63-391.4), while the lowest median 58 nociceptine value was 30.08 (6.96-339.11) in the Drug Overuse Headache group. The median value of the control group was 81.82 (2.13 384.69), and the median value of the Episodic Migraine without Aura group was 83.42 (7.41-396.87). There was no statistically significant difference between migraine groups and the control group in terms of mean values of anandamide. Considering the median values of anandamide (ng / mL), the highest median value was seen in the control group with 15.90 (1.12-192.92). Median values of anandamide were 3,90 (0,89-181,32) in Episodic Migraine without Aura group, while it was 7,64 (1,13-53,1) in Chronic Migraine and 5,18 (0,41-31,9) in Drug Overuse Headache groups. While no significant correlation was found between anandamide levels and headache duration, headache score, MIDAS score and degree in chronic migraine patients; a significant negative correlation was found with monthly headache frequency (r= -0.559; p= 0.030). No significant correlation was observed between anandamide levels and monthly headache frequency, headache duration, headache score and MIDAS score in the Drug Overuse Headache group. Conclusion: Although it could not reach statistical significance, the difference between the median values of anandamide and the lower levels of anandamide compared to controls when all migraine groups were combined, suggest that endo-cannabinoid system dysfunction and anandamide deficiency may have a role in migraine pathophysiology. The inverse correlation we found with the frequency of attacks also suggests that this dysregulation becomes more pronounced as the pain becomes chronic. We found low levels of anandamide and differences in nociceptine levels in our chronic headache groups. If the endo-opioid system is compensatory up-regulated in response to endocannabinoid system dysfunction, patients may be better able to control their analgesic needs. However, if the endo-opioid system cannot be up-regulated for some reason, Drug Overuse Headache may develop with an increase in analgesic intake of patients. Since our results do not have sufficient statistical support, it is not possible to make definitive inferences, but we think that our results can shed light on future studies to be conducted in a larger sample group.