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Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat.
Neuroscience. 2015 Jun 04; 295:103-16.N

Abstract

Voltage-gated sodium channel blockers are not traditionally recommended for osteoarthritis (OA) pain therapy, but given the large peripheral drive that follows OA development there is a rationale for their use. Using a rat model of monosodium iodoacetate (MIA)-induced OA we used in vivo electrophysiology to assess the effects of the Nav1.7- and Nav1.8-selective antagonists, ProTxII and A-803467 respectively, on the evoked activity of spinal dorsal horn neurons in response to electrical, mechanical and thermal stimuli applied to the peripheral receptive field. These studies allow examination of the roles of these channels in suprathreshold stimuli, not amenable to behavioral threshold measures. Spinal administration of ProTxII significantly reduced neuronal responses evoked by mechanical punctate (von Frey (vF) 8-60g) and noxious thermal (45 and 48°C) stimuli in MIA rats only. A-803467 significantly inhibited neuronal responses evoked by vF 8-60g and 48°C heat after spinal administration; significantly inhibited responses evoked by brush, vFs 26-60g and 40-48°C stimuli after systemic administration; significantly inhibited the electrically evoked Aδ-, C-fiber, post-discharge, Input and wind-up responses and the brush, vFs 8-60g and 45-48°C evoked neuronal responses after intra plantar injection in the MIA group. In comparison A-803467 effects in the sham group were minimal and included a reduction of the neuronal response evoked by vF 60g and 45°C heat stimulation after spinal administration, no effect after systemic administration and an inhibition of the evoked response to 45°C heat after intra plantar injection only. The observed selective inhibitory effect of ProTxII and A-803467 for the MIA-treated group suggests an increased role of Nav1.7 and 1.8 within nociceptive pathways in the arthritic condition, located at peripheral and central sites. These findings demonstrate the importance of, and add to, the mechanistic understanding of these channels in osteoarthritic pain.

Authors+Show Affiliations

Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: w.rahman@ucl.ac.uk.Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25818052

Citation

Rahman, W, and A H. Dickenson. "Osteoarthritis-dependent Changes in Antinociceptive Action of Nav1.7 and Nav1.8 Sodium Channel Blockers: an in Vivo Electrophysiological Study in the Rat." Neuroscience, vol. 295, 2015, pp. 103-16.
Rahman W, Dickenson AH. Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat. Neuroscience. 2015;295:103-16.
Rahman, W., & Dickenson, A. H. (2015). Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat. Neuroscience, 295, 103-16. https://doi.org/10.1016/j.neuroscience.2015.03.042
Rahman W, Dickenson AH. Osteoarthritis-dependent Changes in Antinociceptive Action of Nav1.7 and Nav1.8 Sodium Channel Blockers: an in Vivo Electrophysiological Study in the Rat. Neuroscience. 2015 Jun 4;295:103-16. PubMed PMID: 25818052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat. AU - Rahman,W, AU - Dickenson,A H, Y1 - 2015/03/25/ PY - 2014/11/24/received PY - 2015/03/16/revised PY - 2015/03/19/accepted PY - 2015/3/31/entrez PY - 2015/3/31/pubmed PY - 2016/1/14/medline KW - dorsal horn KW - electrophysiology KW - osteoarthritis KW - pain KW - sodium channels SP - 103 EP - 16 JF - Neuroscience JO - Neuroscience VL - 295 N2 - Voltage-gated sodium channel blockers are not traditionally recommended for osteoarthritis (OA) pain therapy, but given the large peripheral drive that follows OA development there is a rationale for their use. Using a rat model of monosodium iodoacetate (MIA)-induced OA we used in vivo electrophysiology to assess the effects of the Nav1.7- and Nav1.8-selective antagonists, ProTxII and A-803467 respectively, on the evoked activity of spinal dorsal horn neurons in response to electrical, mechanical and thermal stimuli applied to the peripheral receptive field. These studies allow examination of the roles of these channels in suprathreshold stimuli, not amenable to behavioral threshold measures. Spinal administration of ProTxII significantly reduced neuronal responses evoked by mechanical punctate (von Frey (vF) 8-60g) and noxious thermal (45 and 48°C) stimuli in MIA rats only. A-803467 significantly inhibited neuronal responses evoked by vF 8-60g and 48°C heat after spinal administration; significantly inhibited responses evoked by brush, vFs 26-60g and 40-48°C stimuli after systemic administration; significantly inhibited the electrically evoked Aδ-, C-fiber, post-discharge, Input and wind-up responses and the brush, vFs 8-60g and 45-48°C evoked neuronal responses after intra plantar injection in the MIA group. In comparison A-803467 effects in the sham group were minimal and included a reduction of the neuronal response evoked by vF 60g and 45°C heat stimulation after spinal administration, no effect after systemic administration and an inhibition of the evoked response to 45°C heat after intra plantar injection only. The observed selective inhibitory effect of ProTxII and A-803467 for the MIA-treated group suggests an increased role of Nav1.7 and 1.8 within nociceptive pathways in the arthritic condition, located at peripheral and central sites. These findings demonstrate the importance of, and add to, the mechanistic understanding of these channels in osteoarthritic pain. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/25818052/Osteoarthritis_dependent_changes_in_antinociceptive_action_of_Nav1_7_and_Nav1_8_sodium_channel_blockers:_An_in_vivo_electrophysiological_study_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(15)00279-1 DB - PRIME DP - Unbound Medicine ER -