Oral administration of Ginkgo biloba extract, EGb-761 inhibits thermal hyperalgesia in rodent models of inflammatory and post-surgical pain

Abstract

Background and purpose: Studies in vitro suggest that the standardised extract of Ginkgo biloba, EGb-761 has anti-inflammatory properties and modulatory effects on key pain-related molecules. This study investigated the analgesic and anti-inflammatory effects of EGb-761 on carrageenan-induced inflammatory and hindpaw incisional pain.

Experimental approach: Adult male Wistar rats (n=6-10/group; 250-420 g) were injected intradermally with carrageenan into the left hindpaw or anaesthetised with isoflurane (2%) and a longitudinal 1 cm incision was made through the skin, fascia and plantaris muscle of the hindpaw. EGb-761 (3, 10, 30, 100 or 300 mg kg(-1)), diclofenac (5 mg kg(-1)) or drug-vehicle was administered 3 h post-carrageenan/post-surgery. Hindpaw withdrawal latency (in seconds) to thermal stimulation, response threshold (in grams) to mechanical stimulation and paw volume were measured.

Key results: Carrageenan induced significant mechanical allodynia, thermal hyperalgesia and paw oedema at 6 h post-carrageenan, while paw incision surgery induced significant mechanical allodynia and thermal hyperalgesia at 6 and 24 h post-surgery. Administration of EGb-761 dose-dependently inhibited thermal hyperalgesia and was equally effective as diclofenac (5 mg kg(-1)) in both the carrageenan and hindpaw incision model. EGb-761 had no effect on carrageenan- or incision-induced mechanical allodynia or paw oedema. Diclofenac significantly reduced mechanical allodynia in both models and carrageenan-induced paw oedema.

Conclusions and implications: EGb-761 dose-dependently alleviates acute inflammatory and surgically induced thermal hyperalgesia and is comparable to diclofenac, a commonly prescribed non-steroidal anti-inflammatory drug. This indicates that EGb-761 has analgesic potential in acute inflammatory pain.

Figure 1

The effect of EGb-761 (Gb), or vehicle administered 3 h post-carrageenan on thermal hyperalgesia. (a) The mean thermal withdrawal latency (in seconds) measured in the ipsilateral hindpaw in adult male rats (n=7–10 per group). Responses were measured before, 2, 4, 6 and 24 h post-carrageenan. Arrow represents time of Gb administration. The results show that 30 mg kg⁻¹ (†††) and 300 mg kg⁻¹ (^***) significantly attenuated hyperalgesia: P<0.001 vs vehicle. (b) The effect of all doses of EGb-761 tested (3, 10, 30, 100 and 300 mg kg⁻¹), diclofenac (5 mg kg⁻¹) or vehicle on thermal hyperalgesia in both hindpaws. Maximum change in response latency in the ipsilateral (ipsi) and contralateral (contra) paw post-carrageenan is represented as mean % change (E_max %) from the pre-carrageenan/baseline response thresholds. Significant attenuation of hyperalgesia: ^*P<0.05; ^***P<0.001 vs vehicle.

Figure 2

The effect of EGb-761 (Gb) or vehicle administered 3 h post-carrageenan on mechanical allodynia. (a) The mean mechanical threshold (in force/g) measured in the ipsilateral hindpaw in adult male rats (n=7–10). Responses were measured before, 2, 4, 6 and 24 h post-carrageenan. Arrow represents time of Gb administration. (b) The effect of all doses of EGb-761 (3, 10, 30 and 300 mg kg⁻¹), diclofenac (5 mg kg⁻¹) or vehicle on mechanical allodynia in both hindpaws. Maximum change in mechanical response threshold in the ipsilateral (ipsi) and contralateral (contra) paw post-carrageenan is represented as mean % change (E_max %) from the pre-carrageenan/baseline response thresholds. EGb-761 had no effect on carrageenan-induced allodynia. Significant attenuation of allodynia by diclofencac; ^***P<0.001 vs vehicle.

Figure 3

The effect of EGb-761 (Gb), diclofenac or vehicle administered 3 h post-carrageenan on paw oedema. Paw volume (cm³) was measured in the ipsilateral and contralateral hindpaws. Paw oedema is represented as the % difference between the ipsilateral and contralateral paw volume. Responses were measured before, 2, 4, 6 and 24 h post-carrageenan. EGb-761 had no effect on carrageenan-induced paw oedema. Significant reduction in paw oedema by diclofenac: ^*P<0.05.

Figure 4

The effect of EGb-761 (Gb) or vehicle administered 3 h post-surgery on thermal hyperalgesia. (a) The mean thermal withdrawal latency (in seconds) measured in the incised paw in adult male rats (n=6–7 per group). Responses were measured before, 2, 4, 6, 24, 48, 72 and 192 h post-surgery. 30 mg kg⁻¹ (†††) and 300 mg kg⁻¹ (^***) significantly attenuated hyperalgesia: P<0.001 vs vehicle. (b) The effect of all doses of EGb-761 (3, 10, 30, 100 and 300 mg kg⁻¹), diclofenac (5 mg kg⁻¹) or vehicle on thermal hyperalgesia. Maximum change in thermal latency in the ipsilateral (ipsi) and contralateral (contra) paw post-surgery is represented as mean % change (E_max %) from the pre-surgery/baseline response thresholds. Significant attenuation of hyperalgesia: ^**P<0.01; ^***P<0.001 vs vehicle. AO, anaesthesia only.

Figure 5

The effect of EGb-761 (Gb) or vehicle administered 3 h post-surgery on mechanical allodynia. (a) The mean mechanical threshold (in force/g) measured in the ipsilateral hindpaw in adult male rats (n=7–10). Responses were measured before, 2, 4, 6, 24, 48, 72 and 192 h post-surgery. Arrow represents time of Gb administration. (b) The effect of all doses of EGb-761 (3, 10, 30, 100 and 300 mg kg⁻¹), diclofenac (5 mg kg⁻¹) or vehicle administered 3 h post-surgery on mechanical allodynia in both hindpaws. Maximum change in mechanical response threshold in the ipsilateral (ipsi) and contralateral (contra) paw post-surgery is represented as mean % change (E_max %) from the pre-surgery/baseline response thresholds. EGb-761 had no effect on paw incision-induced allodynia. AO, anaesthesia only.