Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: An in vivo electrophysiological study

Gerusa D. Dalmolin; Kirsty Bannister; Leonor Gonçalves; Shafaq Sikandar; Ryan Patel; Marta Do Nascimento Cordeiro; Marcus Vinícius Gomez; Juliano Ferreira; Anthony H. Dickenson

doi:10.1097/PR9.0000000000000610

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: An in vivo electrophysiological study

Gerusa D. Dalmolin^*, Kirsty Bannister, Leonor Gonçalves, Shafaq Sikandar, Ryan Patel, Marta Do Nascimento Cordeiro, Marcus Vinícius Gomez, Juliano Ferreira, Anthony H. Dickenson

^*Corresponding author for this work

Wolfson SPaRC

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Introduction: Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives: In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). Methods: In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Results: Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Ad-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Conclusion: Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

Original language	English
Article number	e610
Journal	Pain Reports
Volume	2
Issue number	4
DOIs	https://doi.org/10.1097/PR9.0000000000000610
Publication status	Published - 1 Jul 2017

Keywords

In vivo electrophysiology
Neuropathic pain
Peptide toxin
Spinal cord
Voltage-gated calcium channel

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10.1097/PR9.0000000000000610

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Dalmolin, G. D., Bannister, K., Gonçalves, L., Sikandar, S., Patel, R., Do Nascimento Cordeiro, M., Gomez, M. V., Ferreira, J., & Dickenson, A. H. (2017). Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: An in vivo electrophysiological study. Pain Reports, 2(4), Article e610. https://doi.org/10.1097/PR9.0000000000000610

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title = "Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: An in vivo electrophysiological study",

abstract = "Introduction: Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives: In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). Methods: In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Results: Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Ad-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Conclusion: Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.",

keywords = "In vivo electrophysiology, Neuropathic pain, Peptide toxin, Spinal cord, Voltage-gated calcium channel",

author = "Dalmolin, {Gerusa D.} and Kirsty Bannister and Leonor Gon{\c c}alves and Shafaq Sikandar and Ryan Patel and {Do Nascimento Cordeiro}, Marta and Gomez, {Marcus Vin{\'i}cius} and Juliano Ferreira and Dickenson, {Anthony H.}",

note = "Funding Information: Supported by the Wellcome Trust London Pain Consortium strategic award. G. D. Dalmolin is supported by Capes/ Toxinologia (process 8849-11-0). There are not any financial or other relationships that might lead to a conflict of interest in this study. Publisher Copyright: Copyright {\textcopyright} 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2017",

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doi = "10.1097/PR9.0000000000000610",

language = "English",

volume = "2",

journal = "Pain Reports",

issn = "2471-2531",

publisher = "Lippincott Williams and Wilkins",

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TY - JOUR

T1 - Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats

T2 - An in vivo electrophysiological study

AU - Dalmolin, Gerusa D.

AU - Bannister, Kirsty

AU - Gonçalves, Leonor

AU - Sikandar, Shafaq

AU - Patel, Ryan

AU - Do Nascimento Cordeiro, Marta

AU - Gomez, Marcus Vinícius

AU - Ferreira, Juliano

AU - Dickenson, Anthony H.

N1 - Funding Information: Supported by the Wellcome Trust London Pain Consortium strategic award. G. D. Dalmolin is supported by Capes/ Toxinologia (process 8849-11-0). There are not any financial or other relationships that might lead to a conflict of interest in this study. Publisher Copyright: Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Introduction: Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives: In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). Methods: In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Results: Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Ad-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Conclusion: Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

AB - Introduction: Drugs that counteract nociceptive transmission in the spinal dorsal horn preferentially after nerve injury are being pursued as possible neuropathic pain treatments. In a previous behavioural study, the peptide toxin Tx3-3, which blocks P/Q- and R-type voltage-gated calcium channels, was effective in neuropathic pain models. Objectives: In the present study, we aimed to investigate the effect of Tx3-3 on dorsal horn neuronal responses in rats under physiological conditions and neuropathic pain condition induced by spinal nerve ligation (SNL). Methods: In vivo electrophysiological recordings of dorsal horn neuronal response to electrical and natural (mechanical and thermal) stimuli were made in rats under normal physiological state (naive rats) or after the SNL model of neuropathic pain. Results: Tx3-3 (0.3–100 pmol/site) exhibited greater inhibitory effect on electrical-evoked neuronal response of SNL rats than naive rats, inhibiting nociceptive C-fibre and Ad-fibre responses only in SNL rats. The wind-up of neurones, a measurement of spinal cord hyperexcitability, was also more susceptible to a dose-related inhibition by Tx3-3 after nerve injury. Moreover, Tx3-3 exhibited higher potency to inhibit mechanical- and thermal-evoked neuronal response in conditions of neuropathy. Conclusion: Tx3-3 mediated differential inhibitory effect under physiological and neuropathic conditions, exhibiting greater potency in conditions of neuropathic pain.

KW - In vivo electrophysiology

KW - Neuropathic pain

KW - Peptide toxin

KW - Spinal cord

KW - Voltage-gated calcium channel

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SN - 2471-2531

VL - 2

JO - Pain Reports

JF - Pain Reports

IS - 4

M1 - e610

ER -

Effect of the spider toxin Tx3-3 on spinal processing of sensory information in naive and neuropathic rats: An in vivo electrophysiological study

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