Keywords
Migraine Disorders - Nerve Block - Headache
Palavras-chave
Transtornos de Enxaqueca - Bloqueio Nervoso - Cefaleia
INTRODUCTION
Migraine is a well-defined primary headache syndrome with a prevalence of 17.6% in
women and 5.7% in men.[1]
[2]
This disease, which is quite common in society, results in disability for the patients
and costs for society through drug use and loss of workforce. Although there are many
medical treatment options for reducing the frequency of attacks in migraine patients,
treatment compliance is very low due to the need for long-term drug use and due to
intolerable side-effect profiles. It has been observed[3] that 28.3% of episodic migraine (EM) patients and 44.8% of chronic migraine (CM)
patients use regular medical treatments. Apart from medical treatments, injections
of botulinum toxin have also been used for treating migraine. However, the need for
multiple injections in one session, the need for repetitive injections and the high
costs limit their use.[4]
Peripheral nerve block (PNB) has long been used for treating migraine. Although variations
in the nerves blocked, frequency of use of PNB and anesthetic agents applied have
been reported, this procedure has been found to be effective for treating migraine
in many studies.[5]
[6]
While most studies have been conducted on CM patients, the number of studies on the
efficacy of PNB in EM patients is more limited.[4]
[6]
[7]
[8] Almost all of the latter studies included patients who did not respond to drug treatment,
and the patients who underwent PNB continued to use prophylactic medications.[4]
[5]
[6] Only one study[9] compared patients who underwent greater occipital nerve (GON) block with and without
drug treatment, and this found that there was no difference in efficacy of treatment
between the two groups. In the literature, while there are studies in which GON block
alone was performed, there are others in which it was performed together with supraorbital
nerve (SON) block, which has also been found to be effective.[5]
[6]
[8]
[10]
[11] In addition, while the effects of PNB on the frequency and severity of pain have
been evaluated in studies, the number of studies evaluating the effect on the migraine
disability score is limited.[4]
[5]
[6]
We also perform PNB on migraine patients in our clinic, and in our previously published
study,[12] in line with data in the literature, we found that it was an effective treatment
option. In our clinic, we have sometimes stopped use of prophylactic medications before
PNB in some patients. However, we have only found one study in the literature on the
efficacy of PNB for migraine prophylaxis without drug treatment: Inan et al.[9] observed that there was no difference in terms of efficacy between GON block alone
and in combination with the drug treatment. However, those authors[9] did not report how many patients had EM and how many had CM. In the present study,
we aimed to compare and evaluate the effectiveness of PNB alone and in combination
with prophylactic medications in both EM and CM patients.
METHODS
In the present retrospective study, after obtaining approval from the Ethics Committee
of the Derince Training and Research Hospital (2022-41, May 26, 2022), we reviewed
the files of patients diagnosed with EM and CM in accordance with the International
Classification of Headache Disorders, third edition[2] (ICHD-3), who underwent PNB in our clinic between November 2019 and January 2022.
Patients older than 18 years of age, diagnosed with migraine for at least 1 year,
using the same prophylactic treatment for at least 3 months and having a score on
the Visual Analog Scale (VAS) > 5, were included in the study. Patients who did not
come for their second injection, those who did not come to the follow-ups and those
who were addicted to alcohol and other substances were excluded. We evaluated the
data of 116 patients who met these criteria, among whom 46 were treated with PNB after
discontinuing their prophylactic medication treatment and 70 underwent PNB in combination
with their prophylactic treatment. The prophylactic treatments were discontinued at
least two weeks before the injection in patients followed up with PNB alone.
Procedure
The patients underwent bilateral GON, lesser occipital nerve (LON) and SON blocks
upon admission and in the second week. First, the area to be injected was wiped with
an antiseptic solution. Then, 1.5 mL of 2% lidocaine was injected 2 cm laterally and
2 cm inferiorly to the occipital protuberance for GON block. The LON block was performed
by injecting 1.5 mL of 2% lidocaine at the 2/3 lateral point on a line between the
occipital protuberance and the mastoid; and the SON block was performed by injecting
1 mL of 2% lidocaine just above the supraorbital notch. A 27-G needle was used in
all injections. The patients were monitored for 30 minutes after the procedure to
watch for early side effects. Two weeks later, the same protocol was repeated. The
VAS scores, number of days in pain, number of analgesics taken in the previous month
and Migraine Disability Assessment (MIDAS) scores at baseline and at 2 months were
noted.[13] Dexketoprofen and frovatriptan were prescribed to patients as rescue therapy during
migraine attacks.
The primary outcome was determined in terms of the decrease in the severity of pain
and the number of days in pain, and the secondary outcome consisted of the decrease
in the MIDAS scores.
Statistical analysis
All data were analyzed using the Statistical Package for the Social Sciences (IBM
SPSS Statistics for Windows, IBM Corp., Armonk, NY, United States) software, version
21.0. The data were expressed as numbers, means, standard deviations and medians.
For normally-distributed data, an independent-sample t test was used to evaluate independent groups and paired-sample t tests were used to evaluate repeated measurements. For data that did not show normal
distribution, the Mann-Whitney U test was used to evaluate independent groups and
the Wilcoxon test was used to evaluate repeated measurements. Values of p < 0.05 were considered statistically significant.
RESULTS
A total of 116 patients were included in the study. Out of the 39 EM patients, 21
underwent PNB while continuing to take medications (EM M + PNB group) and 18 underwent
PNB alone (EM PNB group) after their prophylactic medication treatment had been discontinued.
Out of the 77 CM patients, 49 composed the medication plus PNB (CM M + PNB) group
and 28 formed the group with PNB alone (CM PNB).
Evaluation of the data on all the migraine patients regarding the number of days in
pain and the number of analgesics taken in the previous month showed that the VAS
and MIDAS scores of both the PNB and the M + PNB group were significantly lower than
the values found upon admission (p < 0.01). Comparison of the second month data of the two groups did not show any further
significant difference (p > 0.05) ([Table 1]).
Table 1
Comparison of the demographics and treatment efficacy data of the migraine patients
included in the study
|
Peripheral nerve block group (n = 46)
|
Drug treatment + peripheral nerve block group (n = 70)
|
p-value
|
|
Age (years)
|
41.24 ± 11.91
|
39.26 ± 9.73
|
0.32*
|
|
Disease duration (years)
|
12.8 ± 8.76
|
13.0 ± 6.85
|
0.89*
|
|
Sex: Male/Female
|
7/39
|
10/60
|
0.89&
|
|
VAS score upon admission
|
7.91 ± 0.93
|
8.09 ± 0.69
|
0.25*
|
|
VAS score after 2 months
|
4.72 ± 2.69
|
5.37 ± 2.66
|
0.19*
|
|
p
-value
|
0.00#
|
0.00#
|
|
|
MIDAS score upon admission
|
37.02 ± 13.24
|
39.79 ± 12.54
|
0.25*
|
|
MIDAS score after 2 months
|
12.41 ± 10.91
|
11.9 ± 11.43
|
0.81*
|
|
p
-value
|
0.00#
|
0.00#
|
|
|
Number of analgesics taken upon admission
|
17.67 ± 11.87
|
17.91 ± 9.5
|
0.9*
|
|
Number of analgesics taken after 2 months
|
4.13 ± 5.84
|
6.34 ± 8.36
|
0.12*
|
|
p
-value
|
0.00#
|
0.00#
|
|
|
Number of days with pain upon admission
|
18.59 ± 9.2
|
19.13 ± 8.25
|
0.74*
|
|
Number of days in pain after 2 months
|
7.41 ± 8.62
|
7.47 ± 9.02
|
0.97*
|
|
p
-value
|
0.00#
|
0.00#
|
|
Abbreviations: MIDAS, Migraine Disability Assessment; VAS, Visual Analog Scale.
Notes: *independent-sample t test; #paired-sample t test; &chi-square test.
Comparison of all the migraine patients in terms of disease duration, patient age,
VAS and MIDAS scores upon admission, number of days in pain and number of analgesics
taken in the previous month showed that disease duration was significantly longer
in the EM M + PNB group than in the EM PNB group (p = 0.02). There was no significant difference between the groups in terms of other
demographic or baseline clinical data.
Evaluation of the EM and CM patients separately showed that the VAS scores in the
second month, number of analgesics taken in the previous month, MIDAS scores and number
of days in pain were significantly lower in both groups, regardless of the treatment
(p < 0.01). Comparison of the data pertaining to the second month showed that there
was no significant difference between the EM and CM patients, regardless of the treatment
(p > 0.05) ([Table 2]).
Table 2
Evaluation of the demographics and treatment efficacy data among episodic and chronic
migraine patients
|
EM M + PNB group (n = 21)
|
EM PNB group (n = 18)
|
p-value
|
CM M + PNB group (n = 49)
|
CM PNB group (n = 28)
|
p-value
|
|
Age (years)
|
38.43 ± 7.62
|
37.22 ± 10.46
|
0.56*
|
39.61 ± 10.56
|
43.82 ± 12.24
|
0.11$
|
|
Disease duration (years)
|
14.29 ± 6.56
|
9.33 ± 7.52
|
0.02*
|
12.45 ± 6.96
|
15.04 ± 8.9
|
0.16$
|
|
Sex: Male/Female
|
6/15
|
3/15
|
0.37£
|
4/45
|
4/24
|
0.39£
|
|
VAS score upon admission
|
8.05 ± 0.66
|
7.56 ± 0.98
|
0.07#
|
8.1 ± 0.71
|
8.14 ± 0.84
|
0.82$
|
|
VAS after 2 months
|
5.19 ± 3.10
|
4.83 ± 2.81
|
0.58#
|
5.45 ± 2.48
|
4.64 ± 2.57
|
0.18$
|
|
p-value
|
0.001*
|
0.001*
|
|
0.00&
|
0.00&
|
|
|
MIDAS score upon admission
|
29.10 ± 5.90
|
27.61 ± 5.46
|
0.49#
|
44.37 ± 11.84
|
43.07 ± 13.28
|
0.66$
|
|
MIDAS after 2 months
|
8.43 ± 6.48
|
7.72 ± 4.75
|
0.9#
|
13.39 ± 12.76
|
15.43 ± 12.66
|
0.50$
|
|
p
-value
|
0.00*
|
0.00*
|
|
0.00&
|
0.00&
|
|
|
Number of analgesics taken upon admission
|
9.48 ± 5.65
|
9.11 ± 4.25
|
1#
|
21.53 ± 8.49
|
23.18 ± 11.97
|
0.48$
|
|
Number of analgesics taken after 2 months
|
3.67 ± 4.93
|
3.39 ± 3.44
|
0.79#
|
7.49 ± 9.26
|
4.61 ± 6.98
|
0.15$
|
|
p
-value
|
0.003*
|
0.001*
|
|
0.00&
|
0.00&
|
|
|
Number of days in pain upon admission
|
10.1 ± 2.21
|
9.22 ± 2.01
|
0.16#
|
23.0 ± 6.69
|
24.61 ± 6.52
|
0.31$
|
|
Number of days in pain after 2 months
|
4.71 ± 5.01
|
3.94 ± 3.45
|
0.98#
|
8.65 ± 10.09
|
9.64 ± 10.15
|
0.68$
|
|
p
-value
|
0.002*
|
0.001*
|
|
0.00&
|
0.00&
|
|
Abbreviations: CM, chronic migraine; EM, episodic migraine; M + PNB, medications + peripheral
nerve block; MIDAS, Migraine Disability Assessment; PNB, peripheral nerve block alone;
VAS, Visual Analog Scale.
Notes: *Wilcoxon signed-rank test; #Mann-Whitney U test; &paired-sample t test; $independent-sample t test; £chi-square test.
DISCUSSION
In the present study, we showed that bilateral GON, LON and SON block performed twice
in both EM and CM patients, with an interval of two weeks between applications, was
an effective treatment even if the patients only underwent PNB after their drug treatment
had been discontinued.
Although PNB has been shown in many studies[4]
[5]
[7]
[10] to be an effective treatment for migraine, its mechanism of action is still not
fully understood. It is thought that the inflammation that starts with activation
of the trigeminovascular system in migraine attacks causes central sensitization,
from which pain and allodynia then develop.[14] Activation of nociceptors in the dura mater and intracranial vessels and central
projections of the trigeminocervical complex are also thought to play an important
role in pain due to migraine. The GON is a sensory nerve originating predominantly
from the C2 segment. Dural afferents and GON afferents establish anatomical connections.
The SON is an important branch of the ophthalmic nerve (V1), and it receives the sensory
input from the region where migraine pain is most frequently observed.[15] Local anesthetics cause reversible nerve block via voltage-gated sodium channels.
It is thought that PNB reduces peripheral stimulation and central sensitization and
that it regulates the nociceptive pathway; therefore, it is effective.
Many studies[4]
[6]
[16]
[17] have shown that GON block is an effective treatment in migraine patients. Zhang
et al.,[5] in a meta-analysis on randomized controlled studies, showed that GON block in migraine
patients reduced the severity of pain, number of days with pain and number of analgesics
taken, without increasing the risk of side effects.
There is no consensus among previous studies regarding the type of anesthetic agent
to be used or whether additional steroids should be used or not. Ashkenazi et al.[17] and Kashipazha et al.[18] found that there was no significant benefit from use of additional steroid. In a
study by Malekian et al.[19] among EM patients, using triamcinolone alone and triamcinolone injection plus lidocaine,
with a single injection and a one-month follow-up, skin atrophy and alopecia developed
in 3 out of 23 patients, who were then excluded. No significant side effects were
detected in groups that received only lidocaine and saline injection, and significant
superiority of results was found in the groups that received the treatment, in comparison
with the placebo group.[19] Use of lidocaine for GON block was therefore suggested.[19] The agents most commonly used as local anesthetics are lidocaine and bupivacaine.
Bupivacaine was found to be effective in studies using doses of 1.5 mL and 4.5 mL
of 0.5% lidocaine and in studies using doses of 1 mL and 4.5 mL of 2% lidocaine.[17]
[18]
[20]
[21] In the present study, we performed the PNB with 1.5 mL of 2% lidocaine and found
that it was an effective treatment without any significant side effects.
There is no consensus on the frequency of the injections among previous studies. It
has been reported that the efficacy of treatment is maintained for up to eight weeks
in patients who received a single injection.[18] Using a single injection, Dilli et al.[22] found that there was no significant difference in efficacy of treatment, compared
with placebo. Ruiz Piñero et al.[11] and Caputi and Firetto[10] reported that patients who did not benefit from a single block benefited from repeated
blocks.[11] Karadas et al.[23] compared patients who underwent a single block with those who underwent three blocks
once a week and found that the efficacy of treatment, as observed in the 12th week, was better in the group that had undergone repeated blocks. In the present
study, PNB was performed twice, upon admission and in the second week, and we found
that it was an effective treatment, as assessed after two months.
Palamar et al.[24] and Ünal-Artık et al.[25] reported that a single GON block was also effective. Like in most other studies,[5] we performed bilateral PNB.
In many studies,[5]
[6]
[17]
[20]
[24] GON block alone was found to be effective. Caputi and Firetto[10] reported that there was a significant response in 85% of 23 patients with repeated
GON and SON blocks.[10] Ruiz Piñero et al.[11] performed GON and SON blocks according to the origin of pain in 60 patients and
reported that 23 of them responded completely in the second week, while 24 patients
had a partial response. They performed SON block alone in 18 patients, 13 bilaterally
and 5 unilaterally. No separate data were reported regarding the clinical outcomes
among the patients who only underwent SON block.[11] In the study by Özer et al.,[8] in which bilateral GON and SON blocks and placebo were compared among patients taking
prophylactic medications, the proportion of the patients with more than 50% decrease
in the number of painful days in the second month was 65.4% in the EM group, 64.7%
in the CM group and 28.6% in the placebo group. Thus, the treatments were considered
effective. In the present study, we applied SON and LON blocks in addition to GON
block, and we found that this formed an effective treatment on its own, with no need
for prophylactic medications.
In many studies,[8]
[10]
[12]
[16] GON block was performed in patients who did not respond to drug treatment, and these
patients continued to use their medications. We found one study in the literature
in which patients who underwent GON block alone and in combination with prophylactic
medication treatment were evaluated. In that study, conducted by Inan et al.,[9] both groups underwent blocks with weekly 2-mL injection of 0.25% bupivacaine for
the first month and monthly thereafter, and the patients were followed up for 3 months.
No information was provided regarding the proportions of EM and CM patients. In the
third month, GON block was assessed as having been effective in both groups, without
any significant differences in terms of the number of days with pain and the severity
and duration of pain, between the two groups of patients.[9] The present study was the first to evaluate the effectiveness of PNB in both EM
and CM patients who were not taking any drug treatment, and it was the first to assess
MIDAS scores and the effectiveness of SON, LON and GON blocks. We found that there
was no difference in efficacy of treatment between the two groups. Although the prophylactic
medication treatment of the patients who underwent PNB alone was discontinued at least
two weeks before the block, the possibility of a residual effect from these drugs
was a limiting factor of the present study.
The most important limitations of the present study were its retrospective nature,
the absence of a placebo group and the short follow-up. Another limitation was the
lack of knowledge of the prophylactic agents that the patients were taking or had
discontinued, which may have changed the effectiveness of the local anesthetic agent.
The longer duration of diseases in EM M + PNB patients, compared with EM PNB patients,
may have affected the results from our study. One the other hand, the most important
advantage of the present study was that it was the first to evaluate both EM and CM
patients who underwent GON, LON and SON blocks after discontinuation of their drug
treatments.
In conclusion, bilateral GON, LON and SON blocks consisting of lidocaine injection
seemed to be an effective treatment on its own, with no need for prophylactic medications,
in both EM and CM patients during the two-month follow-up. This is an inexpensive
and effective treatment option with low risk of side effects, thereby reducing migraine-related
disability, which is costly both to patients and to society. There is a need to conduct
randomized controlled studies with longer follow-ups and larger samples, in order
to assess the duration of the efficacy of treatment, the frequency of its administration
and the dose of local anesthetic to be administered.
