OBJECTIVE: To investigate the effects of electrical pulses on the ability of methotrexate (MTX) to attenuate inflammation and subsequent joint destruction in rats with adjuvant-induced arthritis (AIA). METHODS: Rats in the experimental group received an intraperitoneal injection of MTX (0.125 mg/kg body weight), followed 30 minutes later by application of direct electrical pulses (50V, 8 Hz) to their left hind paws with an electroporation apparatus (M+/E+ group; n = 8). The procedure was repeated twice weekly for 3 weeks. Three control groups received the following treatments, respectively: MTX without electrical treatment (M+/E- group; n = 9), electrical treatment but no MTX (M-/E+ group; n = 10), or no electrical treatment and no MTX (M-/E- group; n = 9). Progression of AIA was monitored by joint swelling and radiologic and histologic changes in the ankle joint. RESULTS: Three weeks after injection of the adjuvant, and at the height of the arthritic reaction, the swelling and radiologic and histologic changes in the left hind paws in the M+/E+ rats were significantly reduced, as compared with changes observed in the control groups. CONCLUSION: These results demonstrate that application of electrical pulses in combination with use of systemic low-dose MTX can ameliorate local arthritic reactions. This response probably occurs because electrical stimulation promotes transient passage of MTX through pores in the cell membranes, with a resultant local increase in the concentration of the drug within the cells. These results point to a potential use of electrochemotherapy to increase the efficacy of MTX or other drugs in an arthritic joint that is refractory to treatment, without increasing the dose of the drug.
OBJECTIVE: To investigate the effects of electrical pulses on the ability of methotrexate (MTX) to attenuate inflammation and subsequent joint destruction in rats with adjuvant-induced arthritis (AIA). METHODS:Rats in the experimental group received an intraperitoneal injection of MTX (0.125 mg/kg body weight), followed 30 minutes later by application of direct electrical pulses (50V, 8 Hz) to their left hind paws with an electroporation apparatus (M+/E+ group; n = 8). The procedure was repeated twice weekly for 3 weeks. Three control groups received the following treatments, respectively: MTX without electrical treatment (M+/E- group; n = 9), electrical treatment but no MTX (M-/E+ group; n = 10), or no electrical treatment and no MTX (M-/E- group; n = 9). Progression of AIA was monitored by joint swelling and radiologic and histologic changes in the ankle joint. RESULTS: Three weeks after injection of the adjuvant, and at the height of the arthritic reaction, the swelling and radiologic and histologic changes in the left hind paws in the M+/E+ rats were significantly reduced, as compared with changes observed in the control groups. CONCLUSION: These results demonstrate that application of electrical pulses in combination with use of systemic low-dose MTX can ameliorate local arthritic reactions. This response probably occurs because electrical stimulation promotes transient passage of MTX through pores in the cell membranes, with a resultant local increase in the concentration of the drug within the cells. These results point to a potential use of electrochemotherapy to increase the efficacy of MTX or other drugs in an arthritic joint that is refractory to treatment, without increasing the dose of the drug.