Spinal mediation of descending pain inhibitory mechanisms activated by 2/100-Hz electroacupuncture in the rat tail-flick test

Electroacupuncture (EA) has been widely used for the management of chronic pain, but the mechanism of EA-induced analgesia is not yet fully understood. The present study evaluated the effectiveness of intrathecal antagonists of serotonergic (methysergide), α1- (WB4101) and α2- (idazoxan) adrenoceptors, opioid (naloxone), muscarinic (atropine), GABA_A (bicuculline) and GABA_B (phaclofen) receptors in blocking 2/100-Hz electroacupuncture-induced analgesia (EAIA) in the rat tail-flick test. Rats were taken for determination of baseline tail-flick latency (TFL). Vehicle or drug was then injected intrathecally in a volum of 10 μl and EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints under light isoflurane anesthesia. TFL was measured within 30 s after the end of stimulation and at 10-min intervals for up to 60 min. Twenty minutes of 2/100 Hz EA significantly increased TFL. The EAIA was completely inhibited by intrathecal methysergide (30 μg), significantly reduced in intensity and duration by intrathecal idazoxan (50 μg), naloxone (20 μg) or phaclofen (20 μg), and reduced in duration by intrathecal WB4101 (10 μg), atropine (20 μg) or bicuculline (3 μg). The intensity of the 2/100 Hz-EAIA depends on serotonergic and α2-noradrenergic descending mechanisms, and involves spinal opioid and GABA_B modulation. The duration of 2/100 Hz-EAIA depends on both α1- and α2-noradrenergic descending mechanisms, and involves spinal opioid, muscarinic cholinergic, and GABA_A and GABA_B modulation.