Mixed-frequency electroacupuncture produces a distinct pain-relieving mechanism, enhanced by spinal opioid and gamma-aminobutyric acid signalling rather than simply combining low- and high-frequency effects.
The study used a rat tail-withdrawal pain test to assess how spinal administration of drugs affecting norepinephrine, serotonin, endogenous opioids, acetylcholine, and gamma-aminobutyric acid altered pain relief from bilateral electroacupuncture at two leg acupuncture points. Animals received low-frequency, high-frequency, or alternating low-and-high-frequency stimulation, and the duration of reduced pain sensitivity was compared after each drug treatment.
Low-frequency stimulation produced longer-lasting pain relief when norepinephrine, acetylcholine, or gamma-aminobutyric acid availability was increased, whereas high-frequency stimulation was prolonged mainly by increased norepinephrine. Alternating-frequency stimulation was prolonged by enhanced endogenous opioid or gamma-aminobutyric acid signalling and was unaffected by increased serotonin, indicating that it engages a distinct spinal pain-modulation pathway.