Tags

Type your tag names separated by a space and hit enter

Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain.
Front Neurol 2017; 8:163FN

Abstract

BACKGROUND

Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown.

METHODS

Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons.

RESULTS

Both ACh and carbachol significantly increased nociceptive firing in peripheral terminals of meningeal trigeminal nerves recorded by local suction electrode. Strong nociceptive firing was also induced by nicotine, implying essential role of nicotinic AChRs in control of excitability of trigeminal nerve endings. Nociceptive firing induced by carbachol was reduced by muscarinic antagonist atropine, whereas the action of nicotine was prevented by the nicotinic blocker d-tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but not nicotine induced massive degranulation of meningeal mast cells known to release multiple pro-nociceptive mediators. Enzymes terminating ACh action, acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change the firing per se but induced nociceptive activity, sensitive to d-tubocurarine, after pretreatment of meninges with the migraine mediator CGRP. This observation suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine and carbachol induced intracellular Ca2+ transients in trigeminal neurons partially overlapping with expression of capsaicin-sensitive TRPV1 receptors.

CONCLUSION

Trigeminal nerve terminals in meninges, as well as dural mast cells and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic and muscarinic AChRs, which could be activated by the ACh released from parasympathetic nerves. These receptors represent a potential target for novel therapeutic interventions in trigeminal pain and probably in migraine.

Authors+Show Affiliations

Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation.Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Kazan, Russian Federation. Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russian Federation.Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Kazan, Russian Federation. Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russian Federation.Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. Laboratory of Neurobiology, Kazan Federal University, Kazan, Russian Federation.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28496430

Citation

Shelukhina, Irina, et al. "Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain." Frontiers in Neurology, vol. 8, 2017, p. 163.
Shelukhina I, Mikhailov N, Abushik P, et al. Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain. Front Neurol. 2017;8:163.
Shelukhina, I., Mikhailov, N., Abushik, P., Nurullin, L., Nikolsky, E. E., & Giniatullin, R. (2017). Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain. Frontiers in Neurology, 8, p. 163. doi:10.3389/fneur.2017.00163.
Shelukhina I, et al. Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain. Front Neurol. 2017;8:163. PubMed PMID: 28496430.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain. AU - Shelukhina,Irina, AU - Mikhailov,Nikita, AU - Abushik,Polina, AU - Nurullin,Leniz, AU - Nikolsky,Evgeny E, AU - Giniatullin,Rashid, Y1 - 2017/04/27/ PY - 2017/02/10/received PY - 2017/04/07/accepted PY - 2017/5/13/entrez PY - 2017/5/13/pubmed PY - 2017/5/13/medline KW - acetylcholine KW - acetylcholine receptor KW - mast cells KW - meninges KW - migraine KW - nicotine KW - sensory neurons SP - 163 EP - 163 JF - Frontiers in neurology JO - Front Neurol VL - 8 N2 - BACKGROUND: Parasympathetic innervation of meninges and ability of carbachol, acetylcholine (ACh) receptor (AChR) agonist, to induce headaches suggests contribution of cholinergic mechanisms to primary headaches. However, neurochemical mechanisms of cholinergic regulation of peripheral nociception in meninges, origin place for headache, are almost unknown. METHODS: Using electrophysiology, calcium imaging, immunohistochemistry, and staining of meningeal mast cells, we studied effects of cholinergic agents on peripheral nociception in rat hemiskulls and isolated trigeminal neurons. RESULTS: Both ACh and carbachol significantly increased nociceptive firing in peripheral terminals of meningeal trigeminal nerves recorded by local suction electrode. Strong nociceptive firing was also induced by nicotine, implying essential role of nicotinic AChRs in control of excitability of trigeminal nerve endings. Nociceptive firing induced by carbachol was reduced by muscarinic antagonist atropine, whereas the action of nicotine was prevented by the nicotinic blocker d-tubocurarine but was insensitive to the TRPA1 antagonist HC-300033. Carbachol but not nicotine induced massive degranulation of meningeal mast cells known to release multiple pro-nociceptive mediators. Enzymes terminating ACh action, acetylcholinesterase (AChE) and butyrylcholinesterase, were revealed in perivascular meningeal nerves. The inhibitor of AChE neostigmine did not change the firing per se but induced nociceptive activity, sensitive to d-tubocurarine, after pretreatment of meninges with the migraine mediator CGRP. This observation suggested the pro-nociceptive action of endogenous ACh in meninges. Both nicotine and carbachol induced intracellular Ca2+ transients in trigeminal neurons partially overlapping with expression of capsaicin-sensitive TRPV1 receptors. CONCLUSION: Trigeminal nerve terminals in meninges, as well as dural mast cells and trigeminal ganglion neurons express a repertoire of pro-nociceptive nicotinic and muscarinic AChRs, which could be activated by the ACh released from parasympathetic nerves. These receptors represent a potential target for novel therapeutic interventions in trigeminal pain and probably in migraine. SN - 1664-2295 UR - https://www.unboundmedicine.com/medline/citation/28496430/Cholinergic_Nociceptive_Mechanisms_in_Rat_Meninges_and_Trigeminal_Ganglia:_Potential_Implications_for_Migraine_Pain_ L2 - https://dx.doi.org/10.3389/fneur.2017.00163 DB - PRIME DP - Unbound Medicine ER -