|Year : 2018 | Volume
| Issue : 2 | Page : 137-141
Evaluation of Omega-3 fatty acids in management of trigeminal neuralgia
Balwinder Singh1, Ramandeep S Narang1, Kirandeep Kaur2, Soheyl Sheikh3, Jasjeet K Narang4
1 Department of Oral Medicine and Radiology, Oral Pathology, SGRD Institute of Dental Sciences and Research, Amritsar, Punjab, India
2 Department of Oral Surgery, Bibi Kaulan Ji Charitable Hospital, Amritsar, Punjab, India
3 Department of Oral Medicine and Radiology, MM College of Dental Sciences and Research, Mullana, Ambala, Haryana, India
4 Department of Pharmaceutics, Khalsa College of Pharmacy, Amritsar, Punjab, India
|Date of Submission||23-Mar-2018|
|Date of Acceptance||11-Jun-2018|
|Date of Web Publication||16-Jul-2018|
Dr. Balwinder Singh
Department of Oral Medicine and Radiology, SGRD Institute of Dental Sciences and Research, Amritsar, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Trigeminal neuralgic (TN) pain has been known as the world's worst pain. Omega-3 fatty acids have been recently studied extensively in neuralgic pain. Carbamazepine has been known to be the first drug of choice in treating TN pain. In the present study, the potential benefits of omega-3 fatty acids in addition to the carbamazepine were assessed. Objective: The objective of the study was to evaluate the role of omega-3 fatty acids in the neuralgic pain along with carbamazepine in treating neuralgic pain. Materials and Methods: The present study was undertaken on 114 patients with TN pain. The patients were divided in two groups. The group I consisted of patients who were on carbamazepine only, and group II comprised patients who were on carbamazepine and omega-3 fatty acids. The pain was assessed using Brief Pain Inventory questionnaire, which is the most widely used questionnaire for chronic pain. The patients were evaluated on the day of reporting and on subsequent follow-up at 2 weeks, 6 weeks, and 15 weeks interval. The data obtained was subjected to statistical analysis to assess the additional benefits of omega-3 fatty acids in TN pain. Results: The results obtained showed that the intensity of pain reduction and life quality was better in patients receiving carbamazepine and omega-3 fatty acids by the end of the 15th week compared to the patients receiving carbamazepine alone. Conclusion: The present study demonstrates the reduction in neuropathic pain on long-term usage of omega-3 fatty acids, signifying that omega-3 fatty acids may offer better relief in neuralgic pain.
Keywords: Docosahexaenoic acid, eicosapentaenoic acid, neuralgia, omega-3 fatty acids, pain, trigeminal
|How to cite this article:|
Singh B, Narang RS, Kaur K, Sheikh S, Narang JK. Evaluation of Omega-3 fatty acids in management of trigeminal neuralgia. J Indian Acad Oral Med Radiol 2018;30:137-41
|How to cite this URL:|
Singh B, Narang RS, Kaur K, Sheikh S, Narang JK. Evaluation of Omega-3 fatty acids in management of trigeminal neuralgia. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2021 Dec 7];30:137-41. Available from: https://www.jiaomr.in/text.asp?2018/30/2/137/236728
| Introduction|| |
Since the first known description of trigeminal neuralgia (TN) in the second century by Aretaeus of Cappadocia and the first full account of paper on TN published by John Fothergill in 1773, till now in the 21st century, this pain has been often known as world's worst pain. According to the International classification of headache disorders, TN is defined as a disorder characterized by recurrent, unilateral, brief, electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve, and triggered by innocuous stimuli.
The annual overall incidence of TN ranges from 12.6 to 27 people per million per year, with increase in the incidence with advancing age.,, The mechanism of TN has been proposed as hyperexcitability of the trigeminal root fibres near the entry zone into the pons because of mechanical compression by vascular malformations, tumorous origin, or inflammatory demyelination in cases of multiple sclerosis.,,,
The International Headache Society (IHS) divides TN into classic and symptomatic categories. TN is termed classic (or idiopathic) when investigation identifies neurovascular compression and examination shows no clinical evidence. This accounts for 80–90% of TN cases., The term symptomatic (or secondary) is reserved for those patients with TN where major neurological diseases such as multiple sclerosis, skull deformity, or benign compressions in the posterior fossa have been identified.,,,,,,,, Neurological examination may show sensory impairment in trigeminal nerve distribution. The American Academy of Neurology (AAN) and the European Federation of Neurological Societies (EFNS) recommend starting treatment with medicines in patients with classic TN. Surgical procedures should be reserved for patients who are refractory to medicinal therapy or when drugs are causing unacceptable adverse effects. A wide range of medicines have been proposed since 1942 but anticonvulsants have been the main stay in the treatment of neuralgic pain.
Apart from current therapies, home made remedies are also used as an adjunct with medical therapies, which include carrot juice, unsaturated fatty acids, fish liver oil, vitamin B2, almond milk, etc. Omega-3 fish oil and vitamin B-12 have been reported to streng then the cranial nerves, including the TN.
Omega-3 fatty acids also known as n-3 fatty acids are polyunsaturated fatty acids mainly composed of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linolenic acid. The role of polyunsaturated fatty acid (PUFA) has gained role in the suppression of neuropathic pain and have gathered attention of various researchers. Researchers havesuggested that omega-3 fatty acids may be of benefit in neuropathic pain as it hasbeen proposed that the role of the DHA in pain control is because of its dose-dependent anti-nociceptive effects observed in various pain tests and its calming effect on neuropathic pain., The physiological and pharmacological mechanisms of n-3 PUFAs have been studied intensively and the safety of PUFAs has also been established. Therefore, the application of n-3 PUFA in many clinical areas is expected to increase in the future. Hence, in the present study, carbamazepine was supplemented with the omega-3fatty acids to evaluate its possible role in the management of pain in TN patients.
| Materials and Methods|| |
The present study was undertaken on 114 patients who reported to Sri Guru Ramdas Institute of Dental Sciences & Research, Sri Amritsar and Bibi Kaulan ji Charitable Hospital Sri Amritsar, with TN pain divided in two groups of 57 patients each. The minimum age of the patient was 33 years and the maximum age was 69 years. In 114 cases of TN, the maxillary nerve was involved in 48 patients, mandibular nerve in 62 patients, and 4 patients had infra-orbital involvement. However, 13 patients who did not report for the follow up were excluded from the study. The diagnosis of TN was strictly made on the basis of clinical criteria defined by The International Headache Society. According to these criteria, a diagnosis of TN can be made when patient experiences at least three attacks of unilateral facial pain. In addition, pain should have following characteristic: (1) occurring in one or more divisions of the trigeminal nerve, with no radiation beyond the trigeminal distribution; (2) recurring in paroxysmal attacks lasting from a fraction of a second to 2 minutes; (3) severe intensity; (4) electric shock-like, shooting, stabbing, or sharp in quality; (5) precipitated by innocuous stimuli to the affected side of the face; and (6) lack of evidence of any neurologic deficit and a pain that cannot be attributed to another disorder. Approval was taken from the Institutional Ethical Committee and a written informed consent was obtained.
The inclusion criteria included patients who were diagnosed with TN for the first time and who were not on any kind of medication nor were suffering from any systemic disease. The exclusion criteria included those patients who were previously diagnosed for TN and those who had positive systemic history. The patients were given the questionnaire, Modified Brief Pain Inventory (BPI) which is a simple, carefully validated, and widely used questionnaire in the field of chronic pain. One point scale (1–10 range) was used to evaluate the responses given by patients in the questionnaire. The questionnaire dealt with pain intensity and interference of pain in routine activities such as sleeping, walking, and overall mood. This instrument is composed of items on 1-point scale (0–10) on pain intensity and four questions on the interference of pain with general life activities. Patient pain was evaluated with modified-BPI scale on the day the patient reported and current pain score was recorded. The patients were divided into two groups and complete hemogram was performed for both the groups before starting with the medication. Group I consisted of 52 patients who were given carbamazepine 200 mg thrice daily. The group II comprised 49 patients who were given carbamazepine 200 mg along with omega-3 fatty acids 300 mg thrice daily. The patients were followed up and responses were recorded before the start of the treatment (0 day), subsequently at 2 weeks, 6 weeks, and after 15 weeks interval. The data obtained was subjected to statistical analysis.
One female patient reported disturbance in menstrual cycle during first two weeks of study, however, later on no side effect was reported. No adverse effect was reported by any other patient.
| Results|| |
In the present study, the mean age for group II was 60.4 years and for the group I was 57.9 years with no statistical significant difference between the two (P >.05).
The mean score of current pain was 9.1 in group I patients and 9.05 in group II patients. The mean score of the pain at the end of 2nd week, 6th week, and 15th week in group I patients was 5.9, 3.9, and 2.2, respectively. The mean score of pain at the end of 2nd week, 6th week, and 15th week in group II patients was 5.5, 3.5, and 0.8, respectively [Table 1]. When the pain scores were compared between group I and group II at different time intervals, the difference was found to be statistically significant at all time intervals.
To assess the change in percentage of pain reduction between both the two groups, t-test was performed which showed that the reduction in pain percentage was highly significant at end of 15th week in group II patients (P<.005) and nonsignificant at 2nd week and 6th week [Table 2].
|Table 2: Comparison of percentage change at follow up in pain in group I and group II|
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The results obtained showed that the intensity of pain reduction was significant in group II at end of 15th week when compared to group I. However, it was not significant at the end of 2nd and 6th week.
When parameters of pain interference in life activities such as general activity and normal work, sleep, walking ability, and mood & enjoyment of life were compared within the group 1 and group 2, the difference was statistically significant at 2nd week, 6th week, and 15th week interval. However, when groups were compared against each other, i.e., group I versus group II, the results showed that the interference of pain in life activity has significantly reduced at the end of 15th week in group II patients [Table 3]. The results showed that patient started enjoying better life in group II by the end of 15th week compared to group I.
|Table 3: Change in quality of life parameters with pain and on treatment at follow ups|
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| Discussion|| |
A huge variety of pharmacological and surgical treatments are available for TN. The initial treatment of choice for TN is medical therapy, and most patients have at least temporary relief with the use of selected agent. Most studies recommend starting treatment with drugs in patients with classic TN. Surgical procedures should be reserved for patients who are refractory to medical therapy or when the drugs cause unacceptable adverse effects. There are few studies directly comparing medical and surgical treatments. However, pharmacological therapy for TN has been the subject of majority of the studies and available evidence shows carbamazepine is the best-studied treatment and drug of choice for initial and long-term management of classical TN., The first line drugs are carbamazepine (200 to 1200 mg/day) or oxcarbamazepine (600 to 1800 mg/day) second line includes baclofen (40 to 80 mg/day), lamotrigine (100 to 400 mg/day) and third line includes gabapentin (300 to 1800 mg/day), pregabalin (150 to 600 mg/day), topiramate (100 to 400 mg/day), and botox-A (6 to 75 U).
Numerous home remedies are also complemented with the basic treatment of TN which includes omega-3 fatty acid, vitamin B3, vitamin B 12, almond milk. However, recently the use of omega-3 fatty acids containing PUFA, which further contains linolenic acid EPA, and docosahexaenoic acid (DHA) has gathered considerable attention because numerous studies have reported a regulatory role of n-3 PUFAs against inflammatory pain associated with rheumatoid arthritis, dysmenorrhea, and inflammatory bowel disease.,, Tokuyama and Nakamoto have proposed the possible involvement of DHA in pain control because of its dose-dependent antinociceptive effects observed in various pain tests and its calming effect on neuropathic pain. So we decided to supplement the omega-3 fatty acid with carbamazepine to study its potential benefit in neuralgic pain.
The omega-3 fatty acids at a dose of the 900 mg per day was given to the group II patients in three divided dose in addition to carbamazepine 600 mg per day. No significant change in pain was observed in the intensity of pain of at the end of 2nd and 6th week. However, at the end of the 15th week, significant change was observed in the intensity of the pain. The reduction in pain could be due to blocking of activity ofmitogen-activated protein kinase which is involved in the modulation of central sensitization induced by inflammatory and neuropathic pain. Pain reduction by omega-3 fatty acid can also be due to suppressed production of lysophosphatidic acid, which is strongly related to the development of neuropathic pain.
Also, a large proportion of DHA exists as membrane phospholipid in the cortical synaptic membranes and neurons of the central nervous system, hence, intake of omega 3 acid may help in stabilization of the nerve membrane. DHA, is main component of omega 3 fatty acids offers neuroprotection due to reduction in degeneration and demyelination of nerve fibres. Also experiments on various pain models have exhibited dose dependent anti-nociceptive effect on oral administration of DHA.,
The quality of life such as enjoyment of life, sleep patterns, work orientation, mood showed improvement by the end of the 15th week of therapy in group II patients. This was consistent with the study conducted by Ko et al. to investigate the response of neuropathic pain with high oral dose of omega-3 fatty acids. They further reported that these patients had clinically significant pain reduction and improved function as documented with both subjective and objective outcome measures up to as much as 19 months after treatment. This highlighted that omega-3 fatty acids could be of benefit in patients suffering with neuropathic pain.
The results were not significant at the end of 2nd and 6th week. However, the results were statistically significant by the end of 15th week, which indicates that long-term use of omega-3 fatty acids could be more beneficial. There are no so far reported cases for the side-effects of omega 3-acids in the literature available. Similarly in our study only one patient reported that there was a slight delay in regular menstruation cycle in the initial stages of the study which later got normalized. This study done by Ko et al. also reported that there are no major side-effects in patients receiving omega-3 fatty acids.
Several animal studies have shown that dietary fatty acids can modulate acute and chronic nociceptive responses, thus suppressing pain and thermal analgesia suggesting a close association of omega fatty acids with pain control.,
Furthermore, it has been proposed that anti-nociceptive mechanisms of DHA is performed indirectly through the release of an endogenous opioid peptide, β –endorphin but not by directly acting on the opioid receptors. The G-protein-coupled receptor (GPCR) G-protein receptor (GPR) 4039) and GPR120 are activated by omega-3 fatty acids. These receptors are responsible for the regulation of the secretion of opioid peptides such as β–endorphin, which inturn contribute to the antinociception property [Figure 1].
| Conclusion|| |
In conclusion, the present study demonstrates that the reduction in neuropathic pain was more in group 2 who were given omega-3 fatty acids along with carbamazepine, signifying that omega-3 fatty acids have a role to play in pain relief in neuralgic patients. The reduction in neuralgic pain also helps in improving the overall quality of life. However further longitudinal studies are required on larger sample size, over longer duration of time to establish the fact that omega-3 fatty acids have a substantial role to play in alleviating neuralgic pain.
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