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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.

Rahman W, Dickenson AH - Neuroscience (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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

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Neuronal responses evoked by vF 8–60 g and 45 and 48 °C heat stimulation and were significantly reduced by ProTxII in the MIA group only. Comparison of the effects of spinal administration of ProTxII (0.005 and 0.05 μg/50 μl) on the evoked neuronal responses to electrical (a, b), dynamic brush (c, d), mechanical punctate (e, f) and thermal stimulation (g, h) of the peripheral receptive field in sham (n = 8, left panel) and MIA (n = 7, right panel) rats. §Denotes significance at 0.005 μg, and ∗denotes significance at 0.05 μg compared with pre-drug baseline control data, p < 0.05, two-way RM ANOVA with Bonferroni test for multiple paired comparisons. Values are mean ± SEM.
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f0005: Neuronal responses evoked by vF 8–60 g and 45 and 48 °C heat stimulation and were significantly reduced by ProTxII in the MIA group only. Comparison of the effects of spinal administration of ProTxII (0.005 and 0.05 μg/50 μl) on the evoked neuronal responses to electrical (a, b), dynamic brush (c, d), mechanical punctate (e, f) and thermal stimulation (g, h) of the peripheral receptive field in sham (n = 8, left panel) and MIA (n = 7, right panel) rats. §Denotes significance at 0.005 μg, and ∗denotes significance at 0.05 μg compared with pre-drug baseline control data, p < 0.05, two-way RM ANOVA with Bonferroni test for multiple paired comparisons. Values are mean ± SEM.

Mentions: The effect of ProTxII or A-803467, delivered via spinal, systemic or intraplantar route, was assessed upon the evoked responses of deep dorsal horn (Lamina V–VI) neurons to electrical and natural mechanical and thermal stimulation of their peripheral receptive field. Comparison of the average baseline pre-drug responses for MIA and shams per drug and per route of administration (spinal or systemic) revealed a significantly greater C-fiber and vF 60 g evoked response in the MIA group vs sham in the ProTxII study (p < 0.05 Mann–Whitney test, Fig. 1 a vs b); a significantly greater response evoked by 40 °C stimulation in the MIA vs sham group in the A-803467 “systemic” study (p < 0.05 Mann Whitney test, Fig. 3 a vs b) and a significantly greater response evoked by vF 8 g in the MIA vs sham group in the A-803467 “intraplantar” study (p < 0.05 Mann–Whitney test, Fig. 4 a vs b). All other baseline neuronal responses were not significantly different between MIA and sham groups. However, this study was not powered to compare baseline neuronal responses between MIA and sham groups, therefore any differences in the average baseline neuronal responses were not further analyzed or emphasized. Although in an earlier study, where we characterized a large number of cells, we observed, on average, greater firing of neurons in response to mechanical and thermal stimulation in the MIA group, but not to electrical or brush stimuli (Rahman et al., 2009).


Osteoarthritis-dependent changes in antinociceptive action of Nav1.7 and Nav1.8 sodium channel blockers: An in vivo electrophysiological study in the rat.

Rahman W, Dickenson AH - Neuroscience (2015)

Neuronal responses evoked by vF 8–60 g and 45 and 48 °C heat stimulation and were significantly reduced by ProTxII in the MIA group only. Comparison of the effects of spinal administration of ProTxII (0.005 and 0.05 μg/50 μl) on the evoked neuronal responses to electrical (a, b), dynamic brush (c, d), mechanical punctate (e, f) and thermal stimulation (g, h) of the peripheral receptive field in sham (n = 8, left panel) and MIA (n = 7, right panel) rats. §Denotes significance at 0.005 μg, and ∗denotes significance at 0.05 μg compared with pre-drug baseline control data, p < 0.05, two-way RM ANOVA with Bonferroni test for multiple paired comparisons. Values are mean ± SEM.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414363&req=5

f0005: Neuronal responses evoked by vF 8–60 g and 45 and 48 °C heat stimulation and were significantly reduced by ProTxII in the MIA group only. Comparison of the effects of spinal administration of ProTxII (0.005 and 0.05 μg/50 μl) on the evoked neuronal responses to electrical (a, b), dynamic brush (c, d), mechanical punctate (e, f) and thermal stimulation (g, h) of the peripheral receptive field in sham (n = 8, left panel) and MIA (n = 7, right panel) rats. §Denotes significance at 0.005 μg, and ∗denotes significance at 0.05 μg compared with pre-drug baseline control data, p < 0.05, two-way RM ANOVA with Bonferroni test for multiple paired comparisons. Values are mean ± SEM.
Mentions: The effect of ProTxII or A-803467, delivered via spinal, systemic or intraplantar route, was assessed upon the evoked responses of deep dorsal horn (Lamina V–VI) neurons to electrical and natural mechanical and thermal stimulation of their peripheral receptive field. Comparison of the average baseline pre-drug responses for MIA and shams per drug and per route of administration (spinal or systemic) revealed a significantly greater C-fiber and vF 60 g evoked response in the MIA group vs sham in the ProTxII study (p < 0.05 Mann–Whitney test, Fig. 1 a vs b); a significantly greater response evoked by 40 °C stimulation in the MIA vs sham group in the A-803467 “systemic” study (p < 0.05 Mann Whitney test, Fig. 3 a vs b) and a significantly greater response evoked by vF 8 g in the MIA vs sham group in the A-803467 “intraplantar” study (p < 0.05 Mann–Whitney test, Fig. 4 a vs b). All other baseline neuronal responses were not significantly different between MIA and sham groups. However, this study was not powered to compare baseline neuronal responses between MIA and sham groups, therefore any differences in the average baseline neuronal responses were not further analyzed or emphasized. Although in an earlier study, where we characterized a large number of cells, we observed, on average, greater firing of neurons in response to mechanical and thermal stimulation in the MIA group, but not to electrical or brush stimuli (Rahman et al., 2009).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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

Show MeSH
Related in: MedlinePlus