Background: There is a major societal concern relating to the addictive properties of analgesic drugs such as morphine with regard to alleviating pain. Because of this, alternative methods of pain relief are, and have been, actively pursued. An extremely promising method for treatment of low to moderate levels of chronic pain in humans is transcutaneous electrical nerve stimulation (TENS).
Material/Methods: All experiments utilized the invertebrate marine bivalve mollusc Mytilus edulis pedal ganglia. TENS was achieved using a stimulation apparatus developed by Professor Han of Peking University. TENS experiments employed 2 stimulation protocols: 1) low 2 Hz frequency at 5 mA current, 2) alternating low and high frequencies at 2 and 100 Hz, respectively at 5 mA current. Real-time measurements of nitric oxide (NO), using an amperometric probe, measured NO released into the tissue bath subsequent to TENS.
Results: Pooled M. edulis pedal ganglia exposed to TENS demonstrate that stimulation at 2 Hz and 5 mA current promotes time-dependent release of NO. In another experiment, pooled ganglia were stimulated at alternating frequencies of 2 Hz and 100 Hz and 5 mA, which also released NO in a time-dependent manner. Unstimulated control ganglia did not release significant amounts of NO. NO release was antagonized by naloxone and L-NAME exposure, demonstrating that it was receptor and nitric oxide synthase mediated, respectively.
Conclusions: It would appear that TENS stimulates endogenous morphine release since NO release was blocked by naloxone and opioid peptides do not release NO. The present study is highly suggestive of the occurrence of this same mechanism in mammalian neural systems since all biochemical and signaling components are present. Furthermore, it would appear that this process has evolutionary survival value since it occurs in an animal that evolved 500 million years ago.

Keywords: Transcutaneous Electric Nerve Stimulation - methods, Pain - drug therapy, Opioid Peptides - metabolism, Nitric Oxide - metabolism, Neurons - metabolism, Nervous System - metabolism, Naloxone - pharmacology, NG-Nitroarginine Methyl Ester - metabolism, Mytilus edulis - metabolism, Morphine - pharmacology, Models, Biological, Ganglia - metabolism, Calibration, Transcutaneous Electric Nerve Stimulation - methods, Pain - drug therapy, Opioid Peptides - metabolism, Nitric Oxide - metabolism, Neurons - metabolism, Nervous System - metabolism, Naloxone - pharmacology, NG-Nitroarginine Methyl Ester - metabolism, Mytilus edulis - metabolism, Morphine - pharmacology, Models, Biological, Ganglia - metabolism, Calibration