Acetaminophen prevents hyperalgesia in central pain cascade.
Acetaminophen is an analgesic and antipyretic drug believed to exert its effect through interruption of nociceptive processing. In order to determine whether this effect is due to peripheral or central activity, we studied the efficacy of systemic (oral) and intrathecal (IT) application of acetaminophen in preventing the development of hyperalgesia induced through the direct activation of pro-algogenic spinal receptors. Spinal administration of substance P (SP, 30 nmol, IT) in rats produced a decreased thermal threshold, indicating centrally mediated hyperalgesia. Pretreatment of rats with oral acetaminophen (300 mg/kg), but not vehicle, significantly attenuated IT SP-induced hyperalgesia. Acetaminophen given IT also produced a dose-dependent (10-200 microg) antinociceptive effect. In addition, oral acetaminophen suppressed spinal PGE(2) release evoked by IT SP in an in vivo IT dialysis model. The ability of IT as well as oral acetaminophen to reverse this spinally initiated hyperalgesia emphasizes the likely central action and bioavailability of the systemically delivered drug. Jointly, these data argue for an important central antihyperalgesic action of acetaminophen.
Crawley
Brianna
B
Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Saito
Osamu
O
Malkmus
Shelle
S
Fitzsimmons
Bethany
B
Hua
Xiao-Ying
XY
Yaksh
Tony L
TL
D000082:Acetaminophen / Q000008:administration & dosage*; D000284:Administration, Oral; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007278:Injections, Spinal; D008297:Male; D018377:Neurotransmitter Agents / Q000633:toxicity; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000633:toxicity
D018712:Analgesics, Non-Narcotic; D018377:Neurotransmitter Agents; D013373:Substance P; D000082:Acetaminophen; D015232:Dinoprostone