Effect of acute and chronic administration of caffeine on pain-like behaviors in rats with partial sciatic nerve injury.
Caffeine, used in many pain medications as an adjuvant analgesic, is an adenosine A1 and A2A receptor antagonist. Here we examined the effects of acute or chronic caffeine administration in rats after partial sciatic nerve injury. The hindpaw response to mechanical or cold stimulation was assessed following photochemically induced sciatic nerve injury which leads to hypersensitivity to these stimuli. Caffeine was administered i.p. acutely or in the drinking water chronically. The mechanical and cold hypersensitivity of sciatic nerve-injured rats was dose-dependently alleviated by acute systemic administration of caffeine (10-80 mg/kg). The effect of caffeine was, however, associated with side effects including locomotor stimulation or depression. Chronic oral administration (average daily doses 27.5 mg/kg/day or 61.5 mg/kg/day for 2 weeks) of caffeine starting at the time of nerve injury did not significantly affect the development of pain-like behaviors. Thus, acute, but not long term, caffeine intake reduced neuropathic pain state in nerve-injured rats, but only at very high doses. The potential hyperalgesic effect of chronic A1 adenosine receptor blockade may have been compensated for by an antinociceptive effect of caffeine through antagonism of A2A receptors and tolerance development.
Wu
Wei-Ping
WP
Section of Clinical Neurophysiology, Karolinska University Hospital-Huddinge, Karolinska Institutet, S-141 86 Stockholm, Sweden. weiping.wu@labmed.ki.se
Hao
Jing-Xia
JX
Fredholm
Bertil B
BB
Wiesenfeld-Hallin
Zsuzsanna
Z
Xu
Xiao-Jun
XJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications; D013997:Time Factors
D000697:Central Nervous System Stimulants; D002110:Caffeine