Limits...
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.

Show MeSH

Related in: MedlinePlus

Neuronal responses evoked by brush, vF 8–60 g and 48 °C heat were significantly inhibited after spinal administration of A-803467 in the MIA group. Comparison of the effects of topical spinal administration of A-803467 (10 and 50 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 = 6, left panel) and MIA (n = 7, right panel) rats. Asterisks and bars denote statistically significant main effect (one-way RM ANOVA). §Denotes significance at 10 μg, ∗denotes significance at 50 μg compared with 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
getmorefigures.php?uid=PMC4414363&req=5

f0010: Neuronal responses evoked by brush, vF 8–60 g and 48 °C heat were significantly inhibited after spinal administration of A-803467 in the MIA group. Comparison of the effects of topical spinal administration of A-803467 (10 and 50 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 = 6, left panel) and MIA (n = 7, right panel) rats. Asterisks and bars denote statistically significant main effect (one-way RM ANOVA). §Denotes significance at 10 μg, ∗denotes significance at 50 μg compared with baseline control data, p < 0.05, two-way RM ANOVA with Bonferroni test for multiple paired comparisons. Values are mean ± SEM.

Mentions: Spinal administration of A-803467 reduced some of the electrical evoked neuronal responses in both MIA and sham groups, but these effects did not reach significance (Fig. 2a, b). In complete contrast, A-803467 produced a clear MIA group-dependent inhibition of many of the mechanical- and thermal evoked neuronal responses; in particular the mechanical evoked responses in the MIA group were highly sensitive to the inhibitory effects of A-803467 (Fig. 2d, f).


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 brush, vF 8–60 g and 48 °C heat were significantly inhibited after spinal administration of A-803467 in the MIA group. Comparison of the effects of topical spinal administration of A-803467 (10 and 50 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 = 6, left panel) and MIA (n = 7, right panel) rats. Asterisks and bars denote statistically significant main effect (one-way RM ANOVA). §Denotes significance at 10 μg, ∗denotes significance at 50 μg compared with 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

f0010: Neuronal responses evoked by brush, vF 8–60 g and 48 °C heat were significantly inhibited after spinal administration of A-803467 in the MIA group. Comparison of the effects of topical spinal administration of A-803467 (10 and 50 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 = 6, left panel) and MIA (n = 7, right panel) rats. Asterisks and bars denote statistically significant main effect (one-way RM ANOVA). §Denotes significance at 10 μg, ∗denotes significance at 50 μg compared with baseline control data, p < 0.05, two-way RM ANOVA with Bonferroni test for multiple paired comparisons. Values are mean ± SEM.
Mentions: Spinal administration of A-803467 reduced some of the electrical evoked neuronal responses in both MIA and sham groups, but these effects did not reach significance (Fig. 2a, b). In complete contrast, A-803467 produced a clear MIA group-dependent inhibition of many of the mechanical- and thermal evoked neuronal responses; in particular the mechanical evoked responses in the MIA group were highly sensitive to the inhibitory effects of A-803467 (Fig. 2d, f).

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