Repeated intranasal capsaicin applications to treat chronic migraine

Fusco, Bruno M.; Barzoi, G.; Agrò, F.

doi:10.1093/bja/aeg572

Cited by 49 publications

(30 citation statements)

References 8 publications

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“…These treatment options are traditionally based on capsaicin-containing remedies, such as capsaicin cream or high concentration capsaicin patches (Dussor et al, 2014). Intranasal capsaicin administration has also been tested in treating migraine; similar to another TRPV1 agonist civanide, capsaicin reduced the frequency of cluster headache attacks (Diamond et al, 2000; Fusco et al, 2003). In contrast, attempts to identify effective and safe TRPV1 antagonists have been stymied by numerous complications, including dysregulation of internal body temperature.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

et al. 2017

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SUMMARY Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor, TRPV1, is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, irrespective of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble RTX/DkTx. Together our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

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Section: Discussionmentioning

confidence: 99%

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

et al. 2017

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“…The intranasal TRPV1 agonist Civamide showed efficacy for migraine and reduces the frequency of cluster headache attacks. 134 Intranasal capsaicin also showed efficacy for migraine, 135 although the site of action is unknown. However, side effects due to TRPV1 activation within the nasal cavity 134 may ultimately limit the clinical potential of these agents.…”

Section: Transient Receptor Potential V1 (Trpv1)mentioning

confidence: 99%

Targeting TRP Channels For Novel Migraine Therapeutics

Dussor

Yan

Xie

et al. 2014

ACS Chem. Neurosci.

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Migraine is increasingly understood to be a disorder of the brain. In susceptible individuals, a variety of “triggers” may influence altered central excitability, resulting in the activation and sensitization of trigeminal nociceptive afferents surrounding blood vessels (i.e., the trigeminovascular system), leading to migraine pain. Transient receptor potential (TRP) channels are expressed in a subset of dural afferents, including those containing calcitonin gene related peptide (CGRP). Activation of TRP channels promotes excitation of nociceptive afferent fibers and potentially lead to pain. In addition to pain, allodynia to mechanical and cold stimuli can result from sensitization of both peripheral afferents and of central pain pathways. TRP channels respond to a variety of endogenous conditions including chemical mediators and low pH. These channels can be activated by exogenous stimuli including a wide range of chemical and environmental irritants, some of which have been demonstrated to trigger migraine in humans. Activation of TRP channels can elicit CGRP release, and blocking the effects of CGRP through receptor antagonism or antibody strategies has been demonstrated to be effective in the treatment of migraine. Identification of approaches that can prevent activation of TRP channels provides an additional novel strategy for discovery of migraine therapeutics.

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“…One of the first findings that, although indirectly, suggested the role of TRP channels in cluster headache and migraine was represented by the protective effect of the topical, desensitizing application of capsaicin to the patient nasal mucosa [79,80]. Capsaicin treatment couples the unique ability of the drug to first activate, and, subsequently, upon repeated administration, desensitize both the afferent pathway that from channel activation conveys nociceptive signals, and the ‘efferent’ function that results in sensory neuropeptide release [48].…”

Section: Reviewmentioning

confidence: 99%

TRPA1 and other TRP channels in migraine

et al. 2013

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Ever since their identification, interest in the role of transient receptor potential (TRP) channels in health and disease has steadily increased. Robust evidence has underlined the role of TRP channels expressed in a subset of primary sensory neurons of the trigeminal ganglion to promote, by neuronal excitation, nociceptive responses, allodynia and hyperalgesia. In particular, the TRP vanilloid 1 (TRPV1) and the TRP ankyrin 1 (TRPA1) are expressed in nociceptive neurons, which also express the sensory neuropeptides, tachykinins, and calcitonin gene-related peptide (CGRP), which mediate neurogenic inflammatory responses. Of interest, CGRP released from the trigeminovascular network of neurons is currently recognized as a main contributing mechanism of migraine attack. The ability of TRPA1 to sense and to be activated by an unprecedented series of exogenous and endogenous reactive molecules has now been extensively documented. Several of the TRPA1 activators are also known as triggers of migraine attack. Thus, TRP channels, and particularly TRPA1, may be proposed as novel pathways in migraine pathophysiology and as possible new targets for its treatment.

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Repeated intranasal capsaicin applications to treat chronic migraine

Abstract: venous air embolism during epidural catheter insertion. Anesthesiology 1982; 57: 401±12 29 Cohen SM, Laurito CE, Curran MJ. Grand mal seizure in a postpartum patient following infusion of caffeine sodium benzoate to treat persistent headache.

Cited by 49 publications

References 8 publications

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Targeting TRP Channels For Novel Migraine Therapeutics

TRPA1 and other TRP channels in migraine

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