JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

Abstract

Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

Mitochondria and sensory processing in inflammatory and neuropathic pain

“…Oxaliplatin increases cytosolic Ca 2+ by increasing the expression of nonselective cation channel TRPV1 in DRG neurons, thus increasing sensory neurons' excitability. Silencing or blocking TRPV1 reduced both oxaliplatin and paclitaxel induced neuropathic pain (185)(186)(187)(188), which is indirect evidence that mitochondrial Ca 2+ buffering is also involved in chemotherapy-induced neuropathic pain. A role for MCU in mechanical allodynia has been found in mice with painful diabetic neuropathy.…”

The involvement of the noradrenergic system in the antinociceptive effect of cucurbitacin D on mice with paclitaxel-induced neuropathic pain

“…The mice were habituated to the arena for 30 min prior to testing. Von Frey filaments (Stoelting, WI, United States) of different forces (.02–2 g) were then used to determine the 50% withdrawal threshold, as previously described ( Lee et al, 2021 ). Briefly, the filaments were applied perpendicular to the plantar surface of the filament for up to a maximum of 5 s or until licking, flinching, or withdrawal of the paw occurred.…”

Analgesic Effect of SH003 and Trichosanthes kirilowii Maximowicz in Paclitaxel-Induced Neuropathic Pain in Mice

“…For many years, our group has been focusing on CIPN to understand its underlying mechanism of action and to find an effective drug [19,[21][22][23][24]. In particular, we demonstrated that the analgesic effect of oxaliplatin-induced pain could be mediated by activation of the central descending pain-inhibitory system, such as the serotonergic and noradrenergic pathways [19,22,24].…”

“…All behavioral tests were conducted as described in our previous study [21,22]. Cold and mechanical allodynia were measured and quantified using acetone-drop and von-Freyfilament tests, respectively.…”