General Pain Relief using TENS

Q: What is Han Stimulation?

Professor Han investigated the best settings to use for maximum production of the two central opioid peptides associated with pain relief.

In experiments upon rats he found that there was an approximately logarithmic relationship between frequency and opioid release. 

  • Enkephalin had maximum production at about 120 Hz.
  • Dynorphin had maximum production at about 2 Hz.

Stimulation using both frequencies simultaneously had no different effect than using the high frequency only. Shifting between low- and high-frequency stimulation for three seconds each (i.e. 2/100 stimulation) produced a simultaneous activation of the enkephalin and dynorphin systems, inducing a much more potent analgesic effect than that induced by a constant frequency stimulation

Brain functions are regulated by chemical messengers that include neurotransmitters and neuropeptides.

Studies have shown that electrical stimulation in specific frequencies can facilitate the release of specific neuropeptides in the CNS, eliciting profound physiological effects and even activating self-healing mechanisms.

Frequency-dependent neuropeptide release in vitro

In rat experiments stimulation at a frequency such as 15–30 Hz was much more effective than a lower frequency such as 2–3 Hz in triggering peptide release, and burst stimulation was more effective than constant-frequency stimulation.

Furthermore the release of the neuropeptide substance P (SP) per pulse of electrical stimulation was increased by frequencies in the range of 20–50 Hz, whereas release of the small-molecule neurotransmitter 5-hydroxytryptamine (5-HT) per pulse remained constant.

Frequency-dependent release of CNS opioid peptides by peripheral electrical stimulation
Analgesia induced by low-frequency (4 Hz) stimulation, but not that induced by high-frequency (200 Hz) stimulation, can be reversed by low doses of the opioid antagonist naloxone, suggesting that low-frequency stimulation can increase the release of opioid peptides in the CNS.

It was shown that analgesia induced by either low or high frequency stimulation are both mediated by opioid peptides. The difference was that the former was mediated by m and/or d opioid receptors, whereas the latter was mediated by k opioid receptors.

Different kinds of opioid peptides are released under these different conditions.

Studies in rats and humans showing that 2 Hz peripheral stimulation produces a significant increase in  enkephalin but not in that of dynorphin, whereas 100 Hz increases dynorphin but not enkephalin.

To test whether analgesia induced by stimulation at 2 and 100 Hz are mediated differentially in the spinal cord by enkephalin and dynorphin, respectively, an antibody microinjection study was performed.

Enkephalin antiserum resulted in a dramatic decrease in the efficacy of 2 Hz EA analgesia. This effect of antiserum diminished as the EA frequency was increased to 128 Hz. Dynorphin antiserum produced an equally dramatic decrease in the analgesic effect produced by 128 Hz EA, but this effect diminished gradually with decreasing frequency, reaching zero at 4 Hz.  b-endorphin antiserum resulted in an 88% decrease of analgesia at 2 Hz EA and a 61% decrease in analgesia at 15 Hz EA, with no blockade of the analgesic effect of 100 Hz EA.

endomorphin, dose-dependently reduced the analgesia induced by 2 Hz EA stimulation, but not that induced by 100 Hz EA stimulation.

Although high-frequency stimulation is preferable for the release of many CNS peptides, it should not be taken as a gold standard in determining the parameters of electrical stimulation for activating a specific neuropeptide for either experimental or therapeutic purposes.

Clinical verification of laboratory findings

White et al. at the University of Texas Southwestern Medical Center (TX, USA) performed a Observations on the post-operative requirement of opioid analgesics revealed that the alternating-mode stimulation reduced morphine requirement by 53%, whereas a constant low (2 Hz) or constant high (100 Hz) frequency produced only a 32 or 35% decrease, respectively.

Ghoname et al. made similar observations in patients with chronic lower-back pain and found that the alternating mode of stimulation was the most effective in decreasing pain, increasing physical activity and improving the quality of sleep (when compared with the pure low- and pure high-frequency stimulation).


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