Increased hyperalgesia by 5-nitro-2, 3-(phenylpropylamino)-benzoic acid (NPPB), a chloride channel blocker in crush injury-induced neuropathic pain in rats.
Chloride channels belong to diverse group of anion selective channels involved in different signaling processes. The present study was planned to investigate the involvement of chloride channels in crush injury-induced neuropathic pain in rats by using ivermectin, a ligand gated chloride channel opener and NPPB, a CaCC blocker. The effect of ivermectin (5, 10, 20 mg/kg i.p. or 50, 100 and 200 microg/rat by i.c.v. route) and NPPB (10, 20 and 40 mg/kg i.p.) was investigated on pain behavioural thresholds in crush injury-induced neuropathic pain rat model. Reduction in pain threshold by mechanical, thermal and cold stimuli confirmed the development of neuropathic pain in rats after crush injury. Ivermectin administered either by i.p. or i.c.v. route did not alter the pain threshold in mechanical, thermal and, cold allodynia tests in rats. NPPB (20 and 40 mg/kg i.p.) significantly reduced the pain threshold crush injury neuropathic pain model suggesting its hyperalgesic effect. The results showed that NPPB increased significantly the mechanical and thermal hyperalgesia in crush injury-induced neuropathic pain rat model, whereas ivermectin, either by i.p. or i.c.v. route of administration, has no effect on pain symptoms in this model. NPPB hyperalgesic effect is independent of CaCCs inhibition and may be due to blockade of Ca2+-activated K+ channel.
Ramteke
Vinod D
VD
Division of Pharmacology and Toxicology, Indian Veterinary Research Institute Izatnagar, Bareilly, U.P, 243 122, India.
Tandan
Surendra K
SK
Kumar
Dinesh
D
Aruna Devi
R
R
Shukla
Manoj K
MK
Ravi Prakash
Vellanki
V
D020533:Angiogenesis Inhibitors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D003080:Cold Temperature; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology*; D007276:Injections, Intraventricular; D007559:Ivermectin / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009409:Nerve Crush; D009579:Nitrobenzoates; D010146:Pain / Q000473:pathology / Q000523:psychology*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000473:pathology / Q000523:psychology*; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar
D020533:Angiogenesis Inhibitors; D018118:Chloride Channels; D008024:Ligands; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D007559:Ivermectin