Intranasal local anesthetic application: possible mechanisms of action

Abstract

I would like to thank Dr de Leon Casasola for his interest in our daring discourse report on intranasal local anesthetic (INLA) application. I feel like we are more in agreement than not. It is clear from my previous report that intranasal application of local anesthetic is not a true sphenopalatine ganglion (SPG) block based on anatomical and clinical observations. I raised the issue of monitoring a clinical biomarker to confirm parasympathetic SPG blockade in future research. It could be regional cerebral blood flow or lacrimal gland secretion. No doubt that—in some patients— INLA application provides some headache relief. However, the evidence is mixed at best. I offered alternative explanations for possible mechanisms of action that the effect may not be related to the local anesthetic itself and may be related more to nasal mucosa irritation that may modulate the trigeminal autonomic reflex. In fact, after preparing my report, there is a recent randomized controlled trial (RCT) that showed nasal (SPG) block with local anesthetic had no statistically significant effect on pain intensity compared with placebo. However, 50% of patients in both groups had reduced pain and epidural blood patch was avoided. This suggests a major effect not necessarily attributable to local anesthetics. de LeonCasasola et al were interested in this potential theory and stated that “is it possible that nasal mucosa stimulation generates efferent signals that produce a parasympathetic blockade of the SPG? An interesting hypothesis, worth evaluating.” I believe the opposite may hold true. Nasal mucosa stimulation will lead to increase parasympathetic output and lacrimation. In fact, nasal stimulationinduced lacrimation served as a measure of activation of the trigeminal autonomic reflex and the parasympathetic output in recent trials investigating the effects of vagal nerve stimulation. 5 I believe that we need to differentiate between a single nasal spray (which may lead to nasal mucosal stimulation and augmenting the parasympathetic output) and leaving a cottontipped applicator into the nose for a prolonged period of time, which may lead to desensitization and modulation of the trigeminal autonomic reflex. The resulting inhibition of the parasympathetic output may alleviate postdural puncture headache (PDPH) symptoms. Again, this postulated hypothesis needs to be validated. Activation of descending inhibitory pathway and conditioned pain modulatory effects may be another plausible mechanism. This was shown to provide relief for acute migraine headaches. Topical anesthesia may be another likely mechanism. Intranasal local anesthesia is a standard technique used in transnasal surgery as it blocks first and second trigeminal nerve endings in the nasal mucosa. Ethmoidal nerves innervate parts of the dura as well. This explains why intranasal lidocaine in patients with headache is the most effective for pain in the orbital and nasal areas. Moreover, one should not exclude possible placebo effect. Currently, we have two RCTs, showing the effect of intranasal local anesthetic was similar to intranasal saline administration. 8 For detailed explanation of possible mechanisms of actions (Box 1), the reader may want to review the recent lecture on “SPG block and PDPH” during the joint American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) and Society of Obstetric Anesthesia and Perinatology panel at the ASRA 2021 spring meeting.