Determination of current threshold for paw withdrawal with sine-wave electrical stimulation in rats: Effect of drugs and alteration in acute inflammation

Electrical stimulation is widely used to assess the function of sensory nerves in humans. In the present study, the threshold current (CT) required to evoke a paw withdrawal response in rats was assessed with stepwise increases in current delivered as sinusoidal stimulation at frequencies of 2000 Hz (CT2000), 250 Hz (CT250) and 5 Hz (CT5). Baseline CT was 840 ± 3 μA for CT2000, 267 ± 2 μA for CT250 and 165 ± 1 μA for CT5 (n = 59). Intrathecal administration (1-10 μg/rat) of morphine selectively increased CT5 and CT250 (efficacy order was CT5 > CT250 ≫ CT2000 = 0), although systemic morphine (1-5 mg/kg, S.C.) affected all three CTs (CT5 > CT250 > CT2000 > 0). Intrathecal pretreatment at day −3 of capsaicin (75 μg/rat) increased the thermal nociceptive threshold and selectively increased CT5 (CT5 ≫ CT250, CT2000 = 0). Intraplantar carrageenan injection progressively decreased CT250 and CT5, but increased CT2000 for a 3 h period. Intraperitoneal pretreatment with indomethacin (20 mg/kg) attenuated carrageenan evoked CT alterations as well as progression of paw swelling and thermal hyperalgesia. In conclusion, low, but not high, frequency stimulation activated a withdrawal response which appears mediated by morphine and capsaicin sensitive primary afferents and this threshold was reduced in the presence of inflammation. These data suggest the validity of such stimulation in defining drug action in a nontissue injurious fashion.