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
Affiliations
Gerusa D. Dalmolin
aDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Dalmolin is now with Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Sikandar is now with Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
Kirsty Bannister
aDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Dalmolin is now with Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Sikandar is now with Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
Leonor Gonçalves
aDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Dalmolin is now with Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Sikandar is now with Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
Shafaq Sikandar
aDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Dalmolin is now with Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Sikandar is now with Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
Ryan Patel
aDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Dalmolin is now with Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Sikandar is now with Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
Marta do Nascimento Cordeiro
bEzequiel Dias Foundation, Belo Horizonte, MG, Brazil
Marcus Vinícius Gomez
cResearch Institute of Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brazil
Juliano Ferreira
dDepartment of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil
Anthony H. Dickenson
aDepartment of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom. Dalmolin is now with Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, SC, Brazil. Sikandar is now with Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
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 Aδ-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.
