The anti-inflammatory effect of peripheral bee venom stimulation is mediated by central muscarinic type 2 receptors and activation of sympathetic preganglionic neurons

Seo Yeon Yoon; Hyun Woo Kim; Dae Hyun Roh; Young Bae Kwon; Tae Oh Jeong; Ho Jae Han; Hye Jung Lee; Sun Mi Choi; Yeon Hee Ryu; Alvin J. Beitz; Jang Hern Lee

doi:10.1016/j.brainres.2005.05.020

The anti-inflammatory effect of peripheral bee venom stimulation is mediated by central muscarinic type 2 receptors and activation of sympathetic preganglionic neurons

Seo Yeon Yoon, Hyun Woo Kim, Dae Hyun Roh, Young Bae Kwon, Tae Oh Jeong, Ho Jae Han, Hye Jung Lee, Sun Mi Choi, Yeon Hee Ryu, Alvin J. Beitz, Jang Hern Lee

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Abstract

The anti-inflammatory effect (AI) induced by peripheral injection of diluted bee venom (dBV) involves activation of spinal cord circuits and is mediated by catecholamine release from adrenal medulla, but the precise neuronal mechanisms involved are not fully understood. In a recent study, we demonstrated that an increase in spinal acetylcholine is involved in mediating the anti-inflammatory effect of dBV and that this mediation also involves adrenomedullary activation. The present study utilized the mouse air pouch inflammation model to evaluate the involvement of spinal acetylcholine receptors and sympathetic preganglionic neurons (SPNs) in dBV's anti-inflammatory effect (dBVAI). Intrathecal (IT) pretreatment with atropine (muscarinic cholinergic antagonist) but not hexamethonium (nicotinic cholinergic antagonist) significantly suppressed dBVAI on zymosan-evoked leukocyte migration. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic receptor type 2; M₂ antagonist), but not pirenzepine (an M ₁ antagonist) or 4-DAMP (an M₃ antagonist), suppressed the dBVAI. In addition, dBV stimulation specifically increased Fos expression in SPNs of the T7-T11, but not the T1-T6 or T12-L2 spinal cord segments, in animals with zymosan-induced inflammation. Moreover, IT methoctramine pretreatment suppressed this dBV-induced Fos expression specifically in SPNs of T7-T11 level. Peripheral sympathetic denervation using 6-hydroxydopamine (6-OHDA) treatment (which spares sympathetic adrenal medullary innervation) did not alter dBVAI. Collectively these results indicate that dBV stimulation leads to spinal cord acetylcholine release that in turn acts on spinal M₂ receptors, which via a hypothesized disinhibition mechanism activates SPNs that project to the adrenal medulla. This activation ultimately leads to the release of adrenal catecholamines that contribute to dBVAI.

Original language	English (US)
Pages (from-to)	210-216
Number of pages	7
Journal	Brain Research
Volume	1049
Issue number	2
DOIs	https://doi.org/10.1016/j.brainres.2005.05.020
State	Published - Jul 12 2005

Bibliographical note

Funding Information:
This research was supported by a grant (M103KV010009 03K2201 00940) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of Republic of Korea. The publication of the manuscript was also supported by the Korean Institute of Oriental Medicine (KIOM) as well as the Brain Korea 21 project.

Keywords

Adrenomedullary activity
Bee venom
Inflammation
Muscarinic M receptor
Sympathetic preganglionic neuron

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Yoon, S. Y., Kim, H. W., Roh, D. H., Kwon, Y. B., Jeong, T. O., Han, H. J., Lee, H. J., Choi, S. M., Ryu, Y. H., Beitz, A. J., & Lee, J. H. (2005). The anti-inflammatory effect of peripheral bee venom stimulation is mediated by central muscarinic type 2 receptors and activation of sympathetic preganglionic neurons. Brain Research, 1049(2), 210-216. https://doi.org/10.1016/j.brainres.2005.05.020

Yoon, SY, Kim, HW, Roh, DH, Kwon, YB, Jeong, TO, Han, HJ, Lee, HJ, Choi, SM, Ryu, YH, Beitz, AJ & Lee, JH 2005, 'The anti-inflammatory effect of peripheral bee venom stimulation is mediated by central muscarinic type 2 receptors and activation of sympathetic preganglionic neurons', Brain Research, vol. 1049, no. 2, pp. 210-216. https://doi.org/10.1016/j.brainres.2005.05.020

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abstract = "The anti-inflammatory effect (AI) induced by peripheral injection of diluted bee venom (dBV) involves activation of spinal cord circuits and is mediated by catecholamine release from adrenal medulla, but the precise neuronal mechanisms involved are not fully understood. In a recent study, we demonstrated that an increase in spinal acetylcholine is involved in mediating the anti-inflammatory effect of dBV and that this mediation also involves adrenomedullary activation. The present study utilized the mouse air pouch inflammation model to evaluate the involvement of spinal acetylcholine receptors and sympathetic preganglionic neurons (SPNs) in dBV's anti-inflammatory effect (dBVAI). Intrathecal (IT) pretreatment with atropine (muscarinic cholinergic antagonist) but not hexamethonium (nicotinic cholinergic antagonist) significantly suppressed dBVAI on zymosan-evoked leukocyte migration. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic receptor type 2; M2 antagonist), but not pirenzepine (an M 1 antagonist) or 4-DAMP (an M3 antagonist), suppressed the dBVAI. In addition, dBV stimulation specifically increased Fos expression in SPNs of the T7-T11, but not the T1-T6 or T12-L2 spinal cord segments, in animals with zymosan-induced inflammation. Moreover, IT methoctramine pretreatment suppressed this dBV-induced Fos expression specifically in SPNs of T7-T11 level. Peripheral sympathetic denervation using 6-hydroxydopamine (6-OHDA) treatment (which spares sympathetic adrenal medullary innervation) did not alter dBVAI. Collectively these results indicate that dBV stimulation leads to spinal cord acetylcholine release that in turn acts on spinal M2 receptors, which via a hypothesized disinhibition mechanism activates SPNs that project to the adrenal medulla. This activation ultimately leads to the release of adrenal catecholamines that contribute to dBVAI.",

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AU - Lee, Hye Jung

AU - Choi, Sun Mi

AU - Ryu, Yeon Hee

AU - Beitz, Alvin J.

AU - Lee, Jang Hern

N1 - Funding Information: This research was supported by a grant (M103KV010009 03K2201 00940) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of Republic of Korea. The publication of the manuscript was also supported by the Korean Institute of Oriental Medicine (KIOM) as well as the Brain Korea 21 project.

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N2 - The anti-inflammatory effect (AI) induced by peripheral injection of diluted bee venom (dBV) involves activation of spinal cord circuits and is mediated by catecholamine release from adrenal medulla, but the precise neuronal mechanisms involved are not fully understood. In a recent study, we demonstrated that an increase in spinal acetylcholine is involved in mediating the anti-inflammatory effect of dBV and that this mediation also involves adrenomedullary activation. The present study utilized the mouse air pouch inflammation model to evaluate the involvement of spinal acetylcholine receptors and sympathetic preganglionic neurons (SPNs) in dBV's anti-inflammatory effect (dBVAI). Intrathecal (IT) pretreatment with atropine (muscarinic cholinergic antagonist) but not hexamethonium (nicotinic cholinergic antagonist) significantly suppressed dBVAI on zymosan-evoked leukocyte migration. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic receptor type 2; M2 antagonist), but not pirenzepine (an M 1 antagonist) or 4-DAMP (an M3 antagonist), suppressed the dBVAI. In addition, dBV stimulation specifically increased Fos expression in SPNs of the T7-T11, but not the T1-T6 or T12-L2 spinal cord segments, in animals with zymosan-induced inflammation. Moreover, IT methoctramine pretreatment suppressed this dBV-induced Fos expression specifically in SPNs of T7-T11 level. Peripheral sympathetic denervation using 6-hydroxydopamine (6-OHDA) treatment (which spares sympathetic adrenal medullary innervation) did not alter dBVAI. Collectively these results indicate that dBV stimulation leads to spinal cord acetylcholine release that in turn acts on spinal M2 receptors, which via a hypothesized disinhibition mechanism activates SPNs that project to the adrenal medulla. This activation ultimately leads to the release of adrenal catecholamines that contribute to dBVAI.

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The anti-inflammatory effect of peripheral bee venom stimulation is mediated by central muscarinic type 2 receptors and activation of sympathetic preganglionic neurons

Abstract

Bibliographical note

Keywords

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