Non-opioid pathways suppress pain in humans.

Subcutaneous electrical stimulation (SCNS) of median, radial, and saphenous nerves produces prolonged analgesia. The effect of subcutaneous nerve stimulation (SCNS) is not mediated by opiate receptors. (1) There is no cross-tolerance with opiates, and SCNS suppresses pain in patients under chronic meperidine medication. (2) Patients unresponsive to morphine benefit from SCNS. (3) There is no development of tolerance to SCNS. (4) SCNS analgesia is not naloxone-reversible. (5) SCNS can be administered with oral analgesics, either opiate or non-opiate, increasing patient comfort. These observations suggest that non-endorphinergic pathways produce powerful analgesia.