A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats

Abstract

Background: The current therapy of neuropathic pain is inadequate and is limited by the extent of pain relief and the occurrence of dose dependant side effects. Insufficient control of pain with conventional medications prompts the use of complementary and alternative medicine therapies by patients with neuropathic pain. This study therefore investigated a standardized methanolic extract of Bacopa monnieri, a widely reputed nootropic plant, for prospective antinociceptive effect in the chronic constriction injury (CCI) model of neuropathic pain.

Methods: Placement of four loose ligatures around the sciatic nerve produced partial denervation of the hindpaw in rats. Bacopa monnieri (40 and 80 mg/kg, p.o) and the positive control, gabapentin (75 mg/kg, i.p), were administered daily after CCI or sham surgery and the behavioral paradigms of static- and dynamic-allodynia (paw withdrawal threshold to von Frey filament stimulation [PWT] and paw withdrawal latency to light-brushing [PWL]), cold-allodynia (paw withdrawal duration [PWD] to acetone), heat- (PWL to heat-stimulus) and punctate-hyperalgesia (PWD to pin-prick) were assessed on days 3, 7, 14 and 21.

Results: CCI consistently generated static- (days 3-21), dynamic- (days 14-21) and cold-allodynia (days 3-21) plus heat- and mechano-hyperalgesia (days 3-21). The tested doses of Bacopa monnieri significantly attenuated the CCI-induced allodynia and hyperalgesia, exemplified by increased PWT (days 7-21), PWL to light brushing (days 14-21) and heat (days 7-21) as well as decreased PWD to pin prick and cold stimuli (days 3-21). The extract also counterbalanced the CCI-induced aberrations in the nociceptive behaviors by increasing the pain threshold to that of pre-surgery baseline. Gabapentin also afforded analogous beneficial behavioral profile but of higher magnitude.

Conclusions: Our findings suggest that Bacopa monnieri can be used as adjuvant therapy for neuropathic pain conditions afflicted with allodynia and hyperalgesia.

Keywords: Bacopa monnieri; Bacoside-A; Nociception; Pain paradigms; Rat model of neuropathy.

Fig. 1

HPLC-UV fingerprint of bacoside “A” major components (bacoside-A₃, bacopaside-II and bacopasaponin-C) quantified in Bacopa monnieri methanolic extract overlaid with that of standard bacosides

Fig. 2

Effect of Bacopa monnieri methanolic extract (BM-40 and BM-80) and gabapentin (GBP-75) on the maintenance of chronic constriction injury (CCI) induced static allodynia (diminished von Frey filament threshold pressure; PWT in g). Values expressed as mean ± S.E.M. ^### P < 0.001 compared to sham-operated animals, ** P < 0.01, *** P < 0.001 compared to CCI-operated untreated animals, two-way repeated measures ANOVA followed by post hoc Bonferroni analysis. n = 6 rats per group

Fig. 3

Effect of Bacopa monnieri methanolic extract (BM-40 and BM-80) and gabapentin (GBP-75) on the maintenance of chronic constriction injury (CCI) induced dynamic allodynia (diminished paw withdrawal latency to light brushing; PWL in s). Values expressed as mean ± S.E.M. ^### P < 0.001 compared to sham-operated animals, ** P < 0.01, *** P < 0.001 compared to CCI-operated untreated animals, two-way repeated measures ANOVA followed by post hoc Bonferroni analysis. n = 6 rats per group

Fig. 4

Effect of Bacopa monnieri methanolic extract (BM-40 and BM-80) and gabapentin (GBP-75) on the maintenance of chronic constriction injury (CCI) induced heat hyperalgesia (shortened paw withdrawal latency to heat stimulus; PWL in s). Values expressed as mean ± S.E.M. ^### P < 0.001 compared to sham-operated animals, * P < 0.05, ** P < 0.01 compared to CCI-operated untreated animals, two-way repeated measures ANOVA followed by post hoc Bonferroni analysis. n = 6 rats per group

Fig. 5

Effect of Bacopa monnieri methanolic extract (BM-40 and BM-80) and gabapentin (GBP-75) on the maintenance of chronic constriction injury (CCI) induced punctate hyperalgesia (increased paw withdrawal duration to pin prick; PWD in s). Values expressed as mean ± S.E.M. ^### P < 0.001 compared to sham-operated animals, *** P < 0.001 compared to CCI-operated untreated animals, two-way repeated measures ANOVA followed by post hoc Bonferroni analysis. n = 6 rats per group

Fig. 6

Effect of Bacopa monnieri methanolic extract (BM-40 and BM-80) and gabapentin (GBP-75) on the maintenance of chronic constriction injury (CCI) induced cold allodynia (increased paw withdrawal duration to a drop of acetone; PWD in s). Values expressed as mean ± S.E.M. ^### P < 0.001 compared to sham-operated animals, *** P < 0.001 compared to CCI-operated untreated animals, two-way repeated measures ANOVA followed by post hoc Bonferroni analysis. n = 6 rats per group