Anti-allodynic effects of levodopa in neuropathic rats

Abstract

Purpose: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats.

Materials and methods: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not.

Results: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p<0.01). In addition, levodopa induced biphasic analgesia. Different dosage of levodopa did not impact on the rotarod time (p>0.05).

Conclusion: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.

Fig. 1

(A) Time course of paw withdrawal threshold to tactile stimuli in the neuropathic pain model. The withdrawal threshold was measured before (Pre) and after oral administration of distilled water (DW), levodopa 10 mg/kg (L-DOPA10), levodopa 30 mg/kg (L-DOPA30), levodopa 50 mg/kg (L-DOPA50), levodopa 70 mg/kg (L-DOPA70), and levodopa 100 mg/kg (L-DOPA100). The results are expressed as mean±SE (n=10 in each group). ^*p<0.05, ^†p<0.01, ^‡p<0.001, ^§p<0.0001 significantly different from the DW group. (B) Dose-response curve from the peak effects of percentage maximal possible effect (%MPE) for tactile anti-allodynia in the levodopa groups. This shows a dose-dependent tactile anti-allodynic effect. Each line represents mean±SE for 10 rats. Doses (mg/kg) are represented logarithmically on the x-axis and peak %MPE is represented on the y-axis. ^*p<0.05 vs. DW, ^†p<0.01 vs. DW.

Fig. 2

(A) Time course of paw withdrawal frequency to cold stimuli. The response frequencies were measured before (Pre) and after oral administration of distilled water (DW), levodopa 10 mg/kg (L-DOPA10), levodopa 30 mg/kg (L-DOPA30), levodopa 50 mg/kg (L-DOPA50), levodopa 70 mg/kg (L-DOPA70), and levodopa 100 mg/kg (L-DOPA100). The results are expressed as mean±SE (n=10 in each group). ^*p<0.05, ^†p<0.01, ^‡p<0.001, ^§p<0.0001 significantly different from the DW group. (B) Dose-response curve from the peak effects of percentage maximal possible effect (%MPE) for cold anti-allodynia in the levodopa groups. This shows a dose-dependent cold anti-allodynic effect. Each line represents mean±SE for 10 rats. Doses (mg/kg) are represented logarithmically on the x-axis and peak %MPE is represented on the y-axis. ^*p<0.05 vs. DW, ^†p<0.01 vs. DW, ^‡p<0.001 vs. DW.

Fig. 3

(A) Time course of paw withdrawal heat threshold. The heat threshold was measured before (Pre) and after oral administration of distilled water (DW), levodopa 10 mg/kg (L-DOPA10), levodopa 30 mg/kg (L-DOPA30), levodopa 50 mg/kg (L-DOPA50), levodopa 70 mg/kg (L-DOPA70), and levodopa 100 mg/kg (L-DOPA100). The results are expressed as mean±SE (n=6 in each group). ^*p<0.05, ^†p<0.01, ^‡p<0.001, ^§p<0.0001 significantly different from the DW group. (B) Dose-response curves from the peak effects of percentage maximal possible effect (%MPE) for heat anti-allodynia in the levodopa groups. These curves show a dose-dependent heat anti-allodynic effect. Each line represents mean±SE for 6 rats. Doses (mg/kg) are represented logarithmically on the x-axis and peak %MPE is represented on the y-axis. ^*p<0.05 vs. DW, ^†p<0.01 vs. DW, ^‡p<0.001 vs. DW.