Effects of the NMDA-receptor antagonist ketamine on perceptual correlates of long-term potentiation within the nociceptive system.
We recently reported perceptual correlates of long-term potentiation (LTP) of synaptic strength within the nociceptive system demonstrating the functional relevance of LTP for human pain sensation. LTP is generally classified as NMDA-receptor dependent or independent. Here we show that low doses of the NMDA-receptor antagonist ketamine (0.25 mg/kg) prevented the long-term increase in perceived pain to electrical test stimuli, which was induced by high-frequency electrical stimulation (HFS) of nociceptive afferents. Whereas in a control experiment HFS led to a stable increase in perceived pain by 51% for the entire observation period of 1h HFS given 4 min after i.v. ketamine was ineffective. In contrast, HFS induced a two-fold increase of pinprick-evoked pain surrounding the HFS site (secondary neurogenic hyperalgesia) in both experiments. Pain evoked by light tactile stimuli (allodynia) was also unaffected by ketamine. These data support the concept that homotopic hyperalgesia to electrical stimulation of the conditioned pathway is a perceptual correlate of NMDA-receptor sensitive homosynaptic LTP in the nociceptive system, e.g. in the spinal cord. Although secondary neurogenic hyperalgesia and allodynia are induced by the same HFS protocol, they involve additional NMDA-receptor insensitive mechanisms of heterosynaptic facilitation.
Klein
Thomas
T
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Saarstrasse 21, D-55099 Mainz, Germany.
Magerl
Walter
W
Nickel
Ursula
U
Hopf
Hanns-Christian
HC
Sandkühler
Jürgen
J
Treede
Rolf-Detlef
RD
D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D004307:Dose-Response Relationship, Radiation; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D007649:Ketamine / Q000008:administration & dosage*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects*; D010812:Physical Stimulation / Q000009:adverse effects; D011930:Reaction Time / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine