Monitoring of inflammatory biomarkers

Oct 13, 2025 by wbrum.org 56 views

**Correlation of Metalloproteinase-9 Matrix, High Sensitivity C-Reactive Protein, and Serum Glutamate with Pain Intensity After Giving Funarizine in Patients with Tension-Type Chronic Headache**

Background

Tension-Type (TTH) headache is a common and debilitating condition that affects millions of people worldwide. Despite extensive research, the exact cause of TTH remains unclear. However, it is believed that inflammation plays a significant role in the development and maintenance of TTH. Pro-inflammatory mediators, such as cytokines and neurotransmitters, are thought to contribute to the emergence of pain and the sensitization of nerve structures. This assumption is supported by previous studies that have shown that pro-inflammatory mediators are involved in the pathophysiology of primary headache disorders.

The Role of Inflammation in TTH

Inflammation is a complex process that involves the activation of immune cells, the release of pro-inflammatory cytokines, and the production of inflammatory mediators. These mediators can contribute to the development of pain and the sensitization of nerve structures, leading to the assumption that inflammation plays a significant role in the pathophysiology of TTH. Previous studies have shown that pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), are elevated in patients with TTH. These cytokines can contribute to the activation of immune cells, the release of pro-inflammatory mediators, and the production of inflammatory mediators.

The Effectiveness of Flunarizin in TTH

Flunarizin is a calcium channel blocker that has been shown to be effective in the prevention of migraine. However, its effectiveness in the treatment of TTH has not been well studied. Previous studies have shown that flunarizin can reduce the frequency and severity of migraine attacks, but its effectiveness in TTH has not been well established. This study aims to investigate the effectiveness of flunarizin in the treatment of TTH and to explore the correlation between serum levels of metalloproteinase-9 (MMP-9), high sensitivity C-reactive protein (HS-CRP), and glutamate with pain intensity.

Objective

The objective of this study is to explore the effect of flunarizin and amitriptyline on serum levels of MMP-9, HS-CRP, and glutamate in patients with TTH and to investigate the correlation between these levels with the intensity of pain measured using the Numeric Rating Scale (NRS) score.

Method

This experimental study was conducted with a random clinical test design, multiple disguised, and using the pre and post test method. The TTH diagnosis was carried out based on the criteria for the Diagnostic International Classification of Headache Disorders, the second edition (ICHD-II, 2004). Patients who meet the criteria were recruited from H. Adam Malik General Hospital Medan, Green Putri Hospital, and Medan Johor Health Center during the period April to August 2016. Three intervention groups were formed to receive flunarizine 5 mg or 10 mg per day, or amitriptyline 12.5 mg per day for 15 days. Serum levels of MMP-9, HS-CRP, glutamate, and pain intensity were measured before and after treatment.

Results

Of the total 73 patients participating in the study, the majority were women (82.8%), were married (78.1%), and were in the age range of 31-60 years (71.2%). The results showed that after 15 days of treatment, there was a significant decrease in serum levels of MMP-9 and glutamate in all intervention groups. However, there was no significant difference in HS-CRP levels in the flunarizin group of 5 mg and 10 mg. There was a negative correlation between the intensity of pain and HS-CRP levels after the administration of 10 mg flunarizine, while a positive correlation was found between the intensity of pain and glutamate levels after the use of amitriptyline 12.5 mg.

Analysis and Explanation

From the results obtained, it can be concluded that flunarizine and amitriptyline have a significant role in reducing pain intensity in TTH patients. Amitriptyline was proven to be more effective in reducing pain intensity compared to flunarizin, while 5 mg flunarizin was more effective in reducing serum glutamate levels. The relationship between pain intensity and inflammatory marker, especially HS-CRP, shows that inflammation has the potential to play a role in the pain process in TTH patients.

This finding highlights the importance of monitoring inflammatory biomarkers in the management of headache treatment and shows the potential of flunarizin in headache therapy, although more studies are needed to understand their mechanisms and effectiveness more deeply. This study also supports the need for integrated therapy in handling TTH conditions effectively, given the diversity of drug responses in each individual.

Conclusion

In conclusion, this study provides evidence that flunarizine and amitriptyline have a significant role in reducing pain intensity in TTH patients. Amitriptyline was proven to be more effective in reducing pain intensity compared to flunarizin, while 5 mg flunarizin was more effective in reducing serum glutamate levels. The relationship between pain intensity and inflammatory marker, especially HS-CRP, shows that inflammation has the potential to play a role in the pain process in TTH patients. This finding highlights the importance of monitoring inflammatory biomarkers in the management of headache treatment and shows the potential of flunarizin in headache therapy.

Recommendations

Based on the findings of this study, the following recommendations are made:

Monitoring of inflammatory biomarkers: Monitoring of inflammatory biomarkers, such as HS-CRP, should be included in the management of headache treatment to assess the effectiveness of treatment and to identify potential biomarkers for TTH.
Use of flunarizin: Flunarizin should be considered as a potential treatment option for TTH, especially in patients who have not responded to other treatments.
Integrated therapy: Integrated therapy, including the use of flunarizin and amitriptyline, should be considered as a potential treatment option for TTH, given the diversity of drug responses in each individual.
Further studies: Further studies are needed to understand the mechanisms and effectiveness of flunarizin and amitriptyline in the treatment of TTH.

Limitations

This study has several limitations, including:

Small sample size: The sample size of this study was relatively small, which may limit the generalizability of the findings.
Short duration: The duration of this study was relatively short, which may not be sufficient to assess the long-term effectiveness of flunarizin and amitriptyline.
Limited biomarkers: This study only measured a limited number of biomarkers, which may not be sufficient to fully understand the pathophysiology of TTH.

Future Directions

Future studies should aim to:

Increase sample size: Increase the sample size to improve the generalizability of the findings.
Longer duration: Conduct longer duration studies to assess the long-term effectiveness of flunarizin and amitriptyline.
More biomarkers: Measure a wider range of biomarkers to fully understand the pathophysiology of TTH.
Mechanisms of action: Investigate the mechanisms of action of flunarizin and amitriptyline in the treatment of TTH.