Involvement of peripheral opioid receptors in electroacupuncture analgesia for carrageenan-induced hyperalgesia

Acupuncture is widely used to relieve pain; however, the mechanism underlying electroacupuncture analgesia (EAA) during inflammatory pain is unclear. We investigated whether endogenous peripheral opioid receptors participated in EAA during hyperalgesia elicited by carrageenan-induced inflammation. Moreover, we investigated which subtype of opioid receptor was involved in EAA. Carrageenan was subcutaneously administered by intraplanter (i.pl.) injection into the left hind paw. Nociceptive thresholds were measured using the paw pressure threshold (PPT). Rats received 3 Hz electroacupuncture (EA) for 1 h after carrageenan injection. The nonselective peripheral opioid receptor antagonist, naloxone methiodide, was administered by i.pl. injection of the inflamed paw 5 min before EA. Also, animals received i.pl. or intravenous (i.v.) injection of selective antagonists against μ(D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, CTOP), δ(naltrindole, NTI), or κ (nor-Binaltorphimine, nor-BNI) opioid receptors 1 h before EA. PPT decreased significantly 3 h after carrageenan injection. EA resulted in significant increases of PPT, moreover, PPT elevations persisted for 9 h after carrageenan injection. PPT elevations produced by EA were antagonized by local i.pl. injection of naloxone methiodide at 3 and 5 h after cessation of EA. NTI, nor-BNI and CTOP blocked EAA from immediately, 1 h, and 3 h after EA cessation, respectively. The EAA in the inflamed paw could not be blocked by i.v. injection of NTI, nor-BNI and CTOP. These findings suggest that peripheral μ, δ and κ receptors on peripheral nerve terminals are activated by EA, although there is a time difference among these activations.

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► Electroacupuncture relieved inflammatory pain.
► Peripheral μ, δ and κ receptors on peripheral nerve terminals are activated by EA.
► There is a time difference among these activations of the opioid receptors.
► Peripheral opioid receptors involved in electroacupuncture analgesia.