Serotonin involvement in analgesia induced by transcranial electrostimulation.

The experiments described here were intended to investigate whether serotonin (5HT) may be involved in analgesia induced by low current transcranial electrostimulation (TE). The TE stimulus is a 10 mu-ampere, 10 Hz, pulsed current transmitted via electrodes in the pinnae. Combinations of the following were given as intraperitoneal injections: 300 mg/kg p-chlorophenylalanine (pCPA) 48 hours before testing, 100 mg/kg 5-hydroxytryptophan (5HTP) 30 min before testing and the saline vehicle for these drugs. Rats were tested prior to and 30 minutes after TE or sham TE. Testing for analgesia consisted of putting progressively increasing pressure on the rat tail 1/4 inch from the tip with a pneumatically driven, right angle wedge. The amount of pressure at which the rat moved its tail was measured both before and after TE, or sham TE, and recorded as the difference in tolerated peak pressure (DTPP). TE produced analgesia as manifested by a 613 percent increase in DTPP compared with sham TE treatment values. Among TE treated rats, pretreatment with pCPA decreased DTPP 91.5 percent compared with saline control values, indicating 5HT involvement. 5HTP restored TE induced analgesia in pCPA treated rats to the level of saline treated control animals, confirming 5HT involvement.

Low current electrostimulation produces naloxone-reversible analgesia in rats.

A new form of transcranial electrostimulation (TE) has been shown to induce analgesia in rats, as measured by the wet tail flick test. Charge-balanced rectangular current pulses of very low amplitude were delivered bilaterally into low impedance regions of the rat pinnae. The resultant analgesia was studied as a function of systematic variations in stimulus frequency, amplitude and duration. The optimal current for inducing analgesia was found to be 10 microA, well below the startle threshold, and several orders of magnitude below effective stimulus current levels required for other treatment modalities. The optimal stimulation duration was 30 min, during which time a slow onset of analgesia was noted. Significant analgesia persisted for at least 200 min after stimulation ended, and no evidence was found of tolerance developing in the course of 5 daily stimulation sessions. Consistent with findings for other forms of electrostimulation, the analgesic effect of TE was abolished by subcutaneous injection of 3 mg/kg naloxone, suggesting that the mechanism of TE analgesia has an endogenous opioid component.