Long-term antinociception by electroacupuncture is mediated via peripheral opioid receptors in free-moving rats with inflammatory hyperalgesia

Abstract

Background: Electroacupuncture (EA) has been widely accepted and applied as an important acupuncture-related technique for acupuncture analgesia (AA) research. The involvement of opioid peptides and receptors in acute AA has been shown via pre-EA application of opioid receptor/peptide antagonists. In this study, we intended to reproducibly institute acupoint position and needling excluding influences from anaesthesia or restrainers on rats with complete Freund's adjuvant (CFA) hind paw inflammatory pain, as well as to explore opioid-dependency and anti-inflammatory effects in sustained acupuncture analgesia.

Methods: Accurate position and needling approach on acupoint GB30 was modelled by computer-based three-dimensional (3D) images and followed by an optimal EA treatment protocol (100 Hz, 2-3 mA, 20 min) at 0 and 24 h post-CFA in conscious free-moving rats. Opioid receptor antagonists, naloxone (NLX) and naltrindole (NTI) were applied intraplantarly post-EA at late phase (96 h) of CFA. Nociceptive thresholds were assessed by paw pressure threshold (Randall-Sellito) or paw withdrawal latency (Hargreaves), and anti-inflammatory effects were evaluated by measurement of plantar temperature and paw volume.

Results: EA elicited significant sustained mechanical and thermal antinociception up to 144 h. Mechanical antinociception of EA was suppressed by peripheral intraplantar application of NLX and NTI. EA also reduced paw temperature and volume during the same time frame indicating anti-inflammatory effects.

Conclusions: By employing a reproducible EA treatment model on GB30 in free-moving rats, we demonstrated the involvement of peripheral opioid receptors mediated EA-induced long-term antinociception. Future studies should examine the specific neuroimmunological connection of EA-induced sustained antinociception in inflammation.