Analgesic effect of electric stimulation of peripheral nerves with different electric frequencies using the Formalin test

Although electroacupuncture (EA) has been widely used to treat pain, the op timal frequency of EA therapy remains unclear. The study sought to determin e the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injec ted hindpaw of SD rats. Formalin (50 mu l, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive respon se. Behavior, including licking and biting, was observed to have two distin ct periods, an early phase during the first 5 mins and a late phase from 21 -35 mins after injection. The total biting or licking count served as an In dicator of nociceptive response. Our results indicate that ES of the ipsila teral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, wher eas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the e arly phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c .) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after for malin administration. In add ition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The resu lts of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that E S at 2 Hz has a greater analgesic effect on formalin-induced nociceptive re sponse, especially when it is delivered prior to the onset of pain. The ana lgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.