Ranolazine attenuation of CFA-induced mechanical hyperalgesia.
OBJECTIVE
To determine whether ranolazine, a new anti-angina medication, could be an effective analgesic agent in complete Freund's adjuvant-induced inflammatory pain.


BACKGROUND
Plantar injection of complete Freund's adjuvant (CFA) produces an extended period of hyperalgesia that is associated with a dramatic up-regulation of Na(v) 1.7 sodium channels in populations of large and small dorsal root ganglion neurons related to the injection site. Ranolazine appears to produce its anti-angina effect through blocking the late sodium current associated with the voltage-gated sodium channel, Na(v) 1.5. Because ranolazine also inhibits Na(v) 1.7, and 1.8, we sought to determine whether it could be an effective analgesic agent in CFA-induced inflammatory pain.


METHODS
Baseline determinations of withdrawal from thermal and mechanical stimulation were made in Sprague-Dawley rats ( approximately 300-350 x g). Following determination of baseline, one hindpaw in each group was injected with 0.1 mL of CFA. The contralateral paw received saline. Thermal and mechanical stimulation was repeated on the third day post-injection. Vehicle (0.9% isotonic saline; pH 3.0) or ranolazine was then administered in randomized and blinded doses either by intraperitoneal (ip) injection (0, 10, 20, and 50 mg/kg) or by oral gavage (po; 0, 20, 50, 100, and 200 mg/kg). Animals were again tested 30 minutes (ip) and 1 hour (po) after drug administration.


RESULTS
Ranolazine produced dose-dependant analgesia on mechanical allodynia induced by CFA injection, but had no effect on thermal hyperalgesia.


CONCLUSIONS
Ranolazine's potential as a new option for managing both angina and chronic inflammatory pain warrants further study.
Casey
Gregory P
GP
Department of Cell Biology, Health Sciences Center, Louisiana State University, New Orleans, Louisiana, USA.
Roberts
Jomar S
JS
Paul
Dennis
D
Diamond
Ivan
I
Gould
Harry J
HJ
D000083:Acetanilides / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005528:Foot / Q000473:pathology; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D007274:Injections, Intraperitoneal; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D010879:Piperazines / Q000627:therapeutic use*; D000069458:Ranolazine; D051381:Rats; D017207:Rats, Sprague-Dawley
D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D005620:Freund's Adjuvant; D000069458:Ranolazine