Journal of the Neurological Sciences 371 (2016) 149–151
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Journal of the Neurological Sciences
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Letter to the Editor
Efficacy of intravenous lidocaine and
magnesium in intractable trigeminal
neuralgia: A preliminary report
Keywords:
Intravenous lidocaine
Intravenous magnesium
Intractable trigeminal neuralgia
1. Introduction
Trigeminal neuralgia (TN) is described as unilateral pain character-
ized by brief electric shock-like pains, abrupt in onset and termination,
and limited to one or more divisions of the trigeminal nerve [1]. Medi-
cation, such as carbamazepine (CBZ), is often recommended as the
first-line treatment for TN patients [2,3]. Most TN patients benefit
from medical therapy and their pain can be managed effectively for
many years. However, some patients still experience severe and refrac-
tory pain in spite of treatment or experience intolerable side effects as a
result of treatment that preclude their use. In refractory cases, more in-
vasive methods, such as gamma knife, microvascular decompression,
and even destructive or ablative approaches [4,5], are necessary to man-
age TN, but even then a few patients still suffer recurrent and intractable
trigeminal pain. Interestingly, the use of individual or combined intrave-
nous lidocaine and magnesium has been reported to improve pain con-
trol in some patients who suffer with refractory TN [6–7]. Here we
report observations, made on a limited number of subjects with refrac-
tory and postoperative recurrence of TN that was treated with a
protocol that was implemented in our clinic in April 2015. (See Tables
1 and 2.)
2. Cases report
A retrospective analysis was performed on a cohort of subjects that
were treated from April 2015 to December 2015 in Northern Jiangsu
People's Hospital. The diagnosis of TN was based on medical history,
neurologic status, the description of facial pain and/or magnetic reso-
nance imaging evidence of vascular compression of the Gasserian gan-
glion [4,8]. Thirty-three hospitalized patients with a history of severe
facial pain consistent with that reported in TN who had taken either car-
bamazepine (CBZ, 22 patients) or pregabalin (PGB, 4 patients) for up to
18 months or a combination of CBZ and mirtazapine (3 patients) for up
to 8 months were observed.
After suffering poor drug efficacy or intolerable side effects, 33 pa-
tients underwent a surgical procedure to manage their pain (24
1
Contributed to the paper equally.
http://dx.doi.org/10.1016/j.jns.2016.09.017
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microvascular decompressions, 4 destructive surgeries, 5 required
more than 1 type of surgical intervention). Vascular compression of
the Gasserian ganglion was observed in 27 of the 33 patients, but 29 pa-
tients undergoing surgical intervention experienced postoperative pain
relief. Five of the patients that initially reported pain relief after surgery
experienced return of their pain. A combination of lidocaine and magne-
sium [6–7] was administered intravenously to these refractory patients
according to treatment the treatment protocol approved by the North-
ern Jiangsu People's Hospital Institutional Review Board (IRB).
The standard treatment protocol consists of the intravenous infusion
of 1.25 g magnesium and 100 mg lidocaine in 100 ml of normal saline
administered over 1 h, once weekly for a total of 3 weeks. Seven patients
that did not respond to either medical management or surgical inter-
vention were treated with this protocol. Pain intensity was recorded be-
fore and after each infusion and then once weekly for 2 weeks after the
last treatment using a 0–10/10 numeric pain intensity scale. All the sub-
jects experienced pain relief after the combined intravenous infusion
therapy 4 weeks after treatment was complete. Although one of the
subjects experienced recurrence of his pain after 3 months of relief,
complete relief was re-established after re-treatment with the same
protocol.
3. Discussion
TN is characterized by episodes of lancinating pain that occur in the
distribution of 1 or more divisions of the trigeminal nerve and vary in
frequency and intensity over weeks to months. Although patients can
be free of the episodes of lancinating pain, continuous dull pain may
persist [2]. CBZ, a sodium channel blocking agent, is considered first-
line therapy for TN [9]. This medication is often effective but has been
associated frequently with annoying, reversible side effects and some
rare but serious adverse effects that make this option less desirable.
For this reason, newer formulations of sodium channel blockers, e.g.,
oxcarbazepine, or combinations of antiepileptic medications or antiepi-
leptic drugs and other adjuvant agents are used with variable effect.
Despite the fact that 5 patients in our cohort of patients did not ben-
efit from microvascular decompression (1 case of transient relief), this
surgical technique is often effective for treating patients with TN that
fails to respond to pharmacologic options or when only partial relief is
achieved. The protocol for the intravenous administration of lidocaine
and magnesium described in this study may offer a less invasive and po-
tentially safer alternative to MVD or provide hope for patients when the
operation does not produce relief.
It is well established that magnesium and NMDA receptors are in-
volved in pain modulation and central sensitization. NMDA receptors
play a vital role in the activation of induction of central and peripheral
nerve sensitization. Magnesium is an integral component of the resting
NMDA receptor. At resting membrane potentials, magnesium occupies
the pore of the channel and serves to block the flow of sodium and cal-
cium ions through the channel. When the membrane is depolarized in
the presence of glutamate and glycine, the magnesium ion is released
150 Letter to the Editor

Table 1
Demographics of the 7 patients that were treated with combination infusion after surgical intervention had failed to provide pain relief.

No. 1 2 3 4 5 6 7

Gender Female Female Female Male Male Female Female

Age (years) 50 51 51 65 61 45 43
Weight (kg) 45 48 55 60 55 48 50
Trigeminal branch involved II (right) II + III (right) II (right) II (left) III (right) II (right) II (right)
Drug treatment duration 12 months 6 months 11 months 8 months 16 months 3 months 7 months
Drug treatment before CBZ(400-600 mg/day) CBZ(400 mg/day) CBZ(400 mg/day) CBZ(400 mg/day) CBZ(400 mg/day) CBZ(400 mg/day) GBP
surgery and GBP 200 mg/day 200 mg/day)
Surgical techniques MVD MVD MVD+ destructive MVD MVD+ MVD MVD
surgery destructive
surgery
Intraoperative responsible Y Y N Y N Y Y
vessels
Postoperative pain Relief, recurrence No relief Relief, recurrence Relief, recurrence No relief Relief, recurrence Relief,
(3 months) (4 months) (3 months) (2 months) recurrence
(3 months)
Intravenous infusion of 1.25 g + 100 mg 1.25 g + 100 mg 1.25 g + 100 mg 1.25 g + 100 mg 1.25 g + 100 mg 1.25 g + 100 mg
magnesium and
lidocaine
1.25 g + 100 mg

CBZ = carbamazepine; GBP = gabapentin; MVD = microvascular decompression; Y = yes; N = no.

from the channel pore allowing the flow of ions down their concentra- In spite of the positive results, this report has several limitations.
tion gradients. Although the presence of the magnesium ion impedes First, due to the low incidence of intractable TN and to an even lower in-
ion flow, it is not an antagonist in the strict sense of the definition. Per- cidence of intractable cases where MVD failed to provide relief, we were
haps higher concentrations of magnesium in the extracellular compart- not able to identify sufficient numbers of patients for conducting a ran-
ment impede the release of the magnesium ion from the channel pore domized, controlled trial. The consistent and encouraging response to
because the concentration gradient would be steeper. The therapeutic treatment that we observed in just these few subjects persuaded us to
use of magnesium, through both oral and intravenous routes of admin- present our early observations for justification and in anticipation of
istration, has been proven safe and effect for treating many conditions conducting a prospective, multicenter, randomized and placebo-con-
including chronic pain. Lidocaine acts on many pathways when it is ad- trolled trial. Second, we have not been able to determine the effect of in-
ministered intravenously. It increases cerebrospinal fluid acetylcholine fusing either magnesium or lidocaine alone, thus precluding us from
and causes blockade of central sensitization. Lidocaine affects both cen- establishing whether the drug combination produces an additive, an-
tral and peripherally located sodium channels and can thus directly tagonistic or synergistic effect. Nonetheless, these observations support
and/or indirectly modulate central sensitization [6]. These mechanisms the conclusion that the simultaneous intravenous infusion of magne-
account for the application of lidocaine in refractory pains including TN. sium and lidocaine warrants further investigation as a safe and effective
Our study is consistent with a previous report of analgesic efficacy option for managing difficult cases of TN, potentially reducing or pre-
following the intravenous infusion of lidocaine and magnesium. [7]. cluding the need for surgery and other invasive techniques.
The combination protocol provided encouraging results for patients
with intractable TN in this case report. The adverse effects associated Conflict of interest
with the treatment protocol in our study were limited to a single brief
episode of mild dizziness in 1 subject following infusion. Due to the dif- None declared.
ferent mechanisms, the combination of lidocaine and magnesium might
be predicted to have at least an additive effect thus providing a better References
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 Letter to the Editor 151

Min Xu MD Cun-zu Wang MD, PhD⁎

Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Department of Neurosurgery, Northern Jiangsu People's Hospital, Yangzhou
Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese 225001, Jiangsu Province, China
Medicine, Kunshan, 215300, Jiangsu Province, China Corresponding author.
E-mail address: xumin7706@163.com E-mail address: wangcunzu@ujs.edu.cn

Pin Chen MD1 2 August 2016

Department of Neurosurgery, Northern Jiangsu People's Hospital, Yangzhou
225001, Jiangsu Province, China
E-mail address: chenpin1987@126.com

Xun Zhu MM
Department of Neurosurgery, Northern Jiangsu People's Hospital, Yangzhou
225001, Jiangsu Province, China
E-mail address: zhuxun0702@163.com

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