Ibuprofen blocks changes in Na v 1.7 and 1.8 sodium channels associated with complete Freund's adjuvant-induced inflammation in rat

Harry J Gould, John D England, R Denis Soignier, Porter Nolan, Lerna D Minor, Z P Liu, S Rock Levinson, Dennis Paul
Journal of Pain 2004, 5 (5): 270-80

UNLABELLED: Although nerve growth factor plays a role in augmenting sodium channel expression in small dorsal root ganglion (DRG) cells, the cytochemical mediators responsible for enhanced expression in large DRG neurons are unknown. To narrow the search for mediators involved in the increased production of sodium channels in large DRG neurons, we examined the effect of cyclooxygenase inhibition on sodium channel production during inflammation. Thirty minutes before the subcutaneous injection of complete Freund's adjuvant (CFA), rats received ibuprofen (nonselective, cyclooxygenase inhibitor), NS-398 (selective, cyclooxygenase inhibitor), or vehicle. Withdrawal thresholds from thermal and mechanical stimulation were measured before and immediately after CFA injection and at selected hourly intervals after injection for the next 24 hours. Sodium channel up-regulation was then examined in DRG by using site-specific, anti-sodium channel antibodies, Na(v) 1.7 and 1.8. Both ibuprofen and NS-398 provided analgesia during the second phase of inflammatory hyperalgesia that begins 3 hours after CFA injection. The up-regulation, predominantly of Na(v) 1.7 and minimally of Na(v) 1.8 channels, seen in vehicle-treated rats was suppressed by both drugs at 24 hours after injection. By 72 hours after injection, no difference in labeling between the drug- and vehicle-treated animals was observed. Sodium channel labeling in large DRG neurons returned to baseline between 1 and 2 weeks after CFA injection, whereas small cell labeling persisted. The cytochemical signal for sodium channel up-regulation in the large DRG cells that most closely correlates with inflammatory hyperalgesia is mediated at least in part through products of the cyclooxygenase pathway.

PERSPECTIVE: Expression of sodium channels in dorsal root ganglia increases dramatically during inflammation. The increase in sodium channels is thought to enhance neuronal excitability and to play a role in hyperalgesia and wound vigilance during healing. We provide evidence that prostaglandins play a role in signaling channel augmentation.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"