Analgesic Effects of an Ethanol Extract of the Fruits of Xylopia aethiopica and Xylopic Acid in Murine Models of Pain: Possible Mechanism(s)

Effect of Xylopic Acid on Paclitaxel-induced Neuropathic pain in rats

“…Several reports indicate that paclitaxel evokes proinflammatory pain mediators and cytokines, including bradykinin and TNF-α as well as the activation of microglial and astroglial cells (Costa et al, 2011;Burkhart et al, 1994;Manthey et al, 1992;Zhang et al, 2012;Burgos et al, 2012). It has been reported that xylopic acid inhibits the nociceptive effects of bradykinin and glutamate (Woode et al, 2013). The blocking of the effects of these pain mediators may contribute to the observed analgesic properties in the mechanical and thermal hyperalgesia as well as cold allodynia tests.…”

“…In addition, xylopic acid suppresses pain via the opioidergic nociceptive pathway (Woode et al, 2013) and this may partly contribute to the analgesic properties of xylopic acid in this model. Agents such as morphine that blocks the opioidergic nociceptive pathway have been shown to inhibit paclitaxelinduced neuropathic pain (Ami et al, 2012).…”

“…Neuropathic pain was induced in the rats by intraperitoneal (i.p.) injection of paclitaxel (2 mg kg -1 ) dissolved in saline on four alternate days (days 0, 2, 4 and 6) as described by Ameyaw et al, (2013); Flatters and Bennett, (2004). On day 16 postpaclitaxel treatments, xylopic acid (10, 30 and 100 mg kg -1 dissolved in cremophor; groups 1-3), pregabalin (10, 30 and 100 mg kg -1 ; groups 4-6) and cremophore solution (group 7) were administered to the rats after confirmation of neuropathic pain in the various tests.…”

Anti-Nociceptive Synergism of Pregabalin and Xylopic acid Co-administration in Paclitaxel induced Neuropathy: Isobolographic Analysis

“…15 Xylopic acid produces analgesic effect in neuropathic pain by acting on NMDA and adrenergic nociceptive pathways. 12 Any of these nociceptive pathways might have been modulated by xylopic acid in addition to the inhibition of Ca 2+ channel-mediated neurotransmitter release, activation of excitatory amino acid transporters, modulation of potassium channels and inhibition of pathways involving inflammatory mediators by pregabalin to produce the observed synergism in the cold allodynia test. 24 Although xylopic acid and pregabalin co-administration produced analgesic synergism and additivity, the combination may not be without toxic effects, especially on prolong usage.…”

“…The relief of pain by xylopic acid has been attributed to its action on the opioidergic, adrenergic, bradykinin and prostaglandin nociceptive pathways. [10][11][12] Pregabalin, an antiepileptic drug has demonstrated analgesic property in paclitaxel-induced neuropathic pain in pre-clinical, clinical research and therapy.…”