In the absence of a cure for headache, acute treatments continue to be explored, particularly for headaches that are refractory to standard abortive therapies including triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), intravenous (IV) dihydroergotamine (DHE), acetaminophen, aspirin, and antiemetics. IV lidocaine has been widely used in the emergency department (ED) setting as a local anesthesia, as well as in the operating room for perioperative pain management. Recent trials have also demonstrated the efficacy of lidocaine for acute pain from renal colic,1,2 suggesting that it may have a potential place in the acute treatment of primary and secondary headache.

Intravenous Lidocaine

A 2018 review by Berk and Silberstein3 explored the mechanisms of IV lidocaine in headache, pointing to evidence supporting its anti-inflammatory effects and decreased activity of voltage gated sodium channels (VGSCs) involved in the transmission of pain signals through the peripheral nervous system. They found that IV lidocaine infusions used adjunctively with other abortive migraine medications, such as NSAIDs, DHE, magnesium or neuroleptics, produced a full response in 25% of patients and a partial response in 57%.3 The main benefit to IV lidocaine was that combined antinociceptive and antihyperanalgesic effects of other medications improved pain response enough to allow reduced dosing of overused medications. The authors reported that with continuous cardiac monitoring, the combination of medications was effective and reasonably safe.

At the same time, a systematic review by e Silva et al4 of 8 studies of IV lidocaine for pain management in the ED found that while it did improve pain scores for conditions such as renal colic and critical limb ischemia, the evidence did not support significant reductions of pain from migraine headache. Although few adverse effects were reported in most trials, cardiovascular effects from IV lidocaine given as a rapid transfusion were found to develop quickly, requiring careful monitoring.

Intranasal Delivery

Evidence of rapid effectiveness and reduced adverse events coupled with the lack of need for injection or infusion have made intranasal administration of lidocaine an appealing treatment option for headache.5

Peter McAllister, MD, director of the New England Institute for Neurology and Headache and Chief Medical Officer of the New England Institute for Clinical Research in Stamford, Connecticut, explained that intranasal lidocaine might be helpful in the treatment of acute migraine and cluster headache because it blocks the sphenopalatine ganglion (SPG), the largest of 4 parasympathetic ganglia associated with facial pain via the trigeminal nerve. The SPG has preganglionic parasympathetic fibers that interact with postganglionic axons, vasodilator and secretory fibers of the trigeminal nerve and may contribute to migraine pain by releasing neuropeptides that increase parasympathetic cranial blood flow.6

Because the SPG is the only ganglion exposed to the environment via the nasal mucosa, researchers became intrigued by the idea of intranasal delivery of lidocaine to reduce parasympathetic outflow.

Intranasal Lidocaine in the Emergency Department Setting

In their 2017 study of 100 patients age 15 to 55 who were seen in the emergency department (ED) at Golestan Hospital in Ahwaz, Iran, for migraine, Barzegari et al7 found that patients who received 7.5 mg of intravenous chlorpromazine plus 1 mL intranasal lidocaine achieved significantly better pain relief compared with those who received chlorpromazine plus 0.9% normal saline (placebo).

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The Barzegari paper pointed to several previous studies of intranasal lidocaine for acute migraine treatment that indicated rapid relief in some but not all patients, and the results of studies have been mixed. Maizels and Geiger8 in 1999 reported that headache relief was achieved within 15 minutes in 34 of 95 patients (34.8%), with relapse in 7 patients. In 2001, a second randomized controlled trial by Blanda et al9 found no significant difference between lidocaine and placebo for relief of migraine pain in the ED, and Mohammadkarimi and colleagues10 also studied lidocaine use in another ED in Iran and found some reduction in migraine pain, but the effects were not significant compared with placebo, although the authors did recommend lidocaine because of its ease of use. “Intranasal lidocaine is an efficient method for pain reduction in patients with headache. Regarding easy administration and little side effects, we recommend this method in patients referred to ED with headache,” they wrote.

Improving on Lidocaine Delivery

Lidocaine in the IV form is not a standard therapy in the ED setting, and the intranasal formulation has not been widely adopted for acute treatment of headache. Dr McAllister says he rarely uses intranasal lidocaine often in clinical practice. “It’s hard to do as acute treatment for cluster because patients have to lay still, with their head down and instill it. Usually they can’t tolerate it,” he told Neurology Advisor.

Another theory suggests that intranasal treatment in the studies is delivered too late to be effective. Intervention in parasympathetic outflow might be most effective when intranasal lidocaine is given soon after the onset of migraine pain.5

The Barzegari study attributed the lesser efficacy of intranasal lidocaine in some studies to inefficient delivery via the posterior superior region of the nose. “It seems that using a new method that can be applied by the patients themselves without the need for visiting the hospital should be considered more seriously,” they concluded.7

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References

1. Weibel S, Jokinen J, Pace NL, et al. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. Br J Anaesth. 2016;116:770-783.

2. Firouzian A, Alipour A, Rashidian Dezfouli H, et al. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med. 2016;34:443-448.

3. Berk T, Silberstein SD. The use and method of action of intravenous lidocaine and its metabolite in headache disorders. Headache. 2018;58:783-789.

4. e Silva LOJ, Scherber K, Cabrera D, et al. Safety and efficacy of intravenous lidocaine for pain management in the emergency department: a systematic review. Ann Emerg Med. 2018;72:135-144.e3.

5. Avcu N, Doğan NO, Pekdemir M, et al. Intranasal lidocaine in acute treatment of migraine: a randomized controlled trial. Ann Emerg Med. 2017;69:743-751.

6. Ernest EA III. Sphenopalatine Ganglion Neuralgia Diagnosis and Treatment. Practical Pain Management.  https://www.practicalpainmanagement.com/pain/other/sphenopalatine-ganglion-neuralgia-diagnosis-treatment. Updated December 28, 2011. Accessed March 6, 2019.

7. Barzegari H, Motamed H, Ziapour B, Hajimohammadi M, Kadhodazadeh M. Intranasal lidocaine for primary headache management in emergency department; a clinical trial. Emerg (Tehran.) 2017;5(1):e79.

8. Maizels M, Geiger AM. Intranasal lidocaine for migraine: a randomized trial and open-label follow-up. Headache. 1999;39:543-551.

9. Blanda M, Rench T, Gerson LW, Weigand JV. Intranasal lidocaine for the treatment of migraine headache: a randomized, controlled trial. Acad Emerg Med. 2001;8:337-342.

10. Mohammadkarimi N, Jafari M, Mellat A, Kazemi E, Shirali A. Evaluation of efficacy of intra-nasal lidocaine for headache relief in patients refer to emergency department. J Res Med Sci. 2014;19:331-335.

This article originally appeared on Neurology Advisor