Inflammatory
pain and
neuropathic pain are major health issues that represent considerable social and economic burden worldwide. In this study we investigated the potential of
obtusifolin and
gluco-obtusifolin, two
anthraquinones found in the seeds of the widely used traditional Chinese medical botanical Cassia obtusifolia, to reduce neuropathic and inflammatory
pain. The potential
analgesic effects of
obtusifolin and
gluco-obtusifolin were evaluated by mice
formalin test and complete
Freund's adjuvant (CFA)-induced nociceptive behaviors in rats. Chronic constriction injury (CCI), L5 spinal nerve
ligation (L5 SNL), diabetes, and chemotherapeutics inducing
allodynia were used to test whether repeated treatment with
obtusifolin and
gluco-obtusifolin ameliorated
neuropathic pain. Finally, we explored whether
obtusifolin and
gluco-obtusifolin altered the degree of
neuroinflammation in rat spinal cord after CFA administration and CCI induction.
Obtusifolin and
gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reduced licking/biting time in dose-dependent manner in phase 2 of
formalin-induced behavior in mice. Furthermore, repeated administration of
obtusifolin and
gluco-obtusifolin (0.25, 0.5, 1, and 2 mg/kg) reversed
mechanical allodynia induced by CFA, CCI, L5 SNL, diabetes, and
oxaliplatin in a dose-dependent manner in rats. Levels of activated
nuclear factor-kappa B (NF-κB) and proinflammatory
cytokines (
interleukin (IL)-1β, IL-6,
tumor necrosis factor α (TNF-α)) in lumbar spinal cord were elevated in rats following CFA treatment and CCI induction, and
obtusifolin and
gluco-obtusifolin significantly inhibited these effects. Our results demonstrate that
obtusifolin and
gluco-obtusifolin produce significant antinociceptive action in rodent behavioral models of inflammatory/
neuropathic pain, and that this activity is associated with modulation of
neuroinflammation in spinal cord.