Selective inhibitory effects of pregabalin on peripheral C but not A-delta fibers mediated nociception in intact and spinalized rats.
Effects of pregabalin (PGB, 20-80 mg/kg i.v. injection) on spinally-organized nociception were investigated in isoflurane-anesthetized intact and spinalized rats. Responses of single deep spinal dorsal horn (DH) (laminae IV-V) nociceptive-specific (NS) neurons receiving peripheral inputs from A-delta and C fibers to repetitive electrical stimulation (intensity: 3-5 mA; frequency: 1 Hz; pulse duration: 1 ms), mechanical/heat stimulation were recorded extracellularly during physiological condition and s.c. bee venom (BV) induced inflammation. PGB significantly inhibited C-fiber mediated spinal NS neurons' late responses including phenomena of wind-up (temporal summation) and after-discharge. However, the antinociceptive effects of PGB on nociception were not observed until 30 min after its administration. In contrast, no significant inhibitory effect of PGB on A-delta fiber mediated early responses was observed during the experiments. Compared with intact rats, the inhibitory effects of PGB upon nociception vanished in the spinalized animals. This suggests that PGB-induced selective antinociceptive effect on C-fiber mediated nociception is mainly central effects involving supraspinal centers via descending inhibitory controls. Furthermore, pre-treatment, but not post-treatment, with PGB (80 mg/kg) markedly inhibited s.c. BV elicited spontaneous neuronal responses, and noxious mechanical/heat stimuli evoked hyperactivities of spinal NS neurons, indicating that PGB has efficacy of pre-emptive analgesia on pathological pain associated with central sensitization.
Center for Biomedical Research on Pain, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, PR China. yhj@mail.xjtu.edu.cn
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Arendt-Nielsen
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003655:Decerebrate State; D004558:Electric Stimulation; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects* / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D000069583:Pregabalin; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000927:Anticonvulsants; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid