<p>The Antiallodynic Effect of Nefopam on Vincristine-Induced Neuropathy in Mice</p>

Abstract

Background: Chemotherapy-induced neuropathic pain is a disabling condition following cancer treatment. Vincristine has more neurotoxicity than other vinca alkaloid agents. This study evaluated the correlation of different doses of nefopam with antiallodynic effects in a mouse vincristine neuropathy model. Methods: A peripheral neuropathic mouse model was made by intraperitoneal injection of vincristine (0.1 mg/kg/day; 5-day-on, 2-day-off schedule over 12 days). After the development of allodynia, mice were injected intraperitoneally with 0.9% normal saline (NS group) or various doses (10, 30, 60 mg/kg) of nefopam (Nefopam group). We examined allodynia using von Frey hairs pre-administration and at 30, 60, 90, 120, 180, 240 mins, and 24 hrs after drug administration. We also measured the neurokinin-1 receptor concentrations in the spinal cord to confirm the antiallodynic effect of nefopam after drug administration. Results: The peripheral neuropathic mouse model showed prominent mechanical allodynia. Intraperitoneal nefopam produced a clear dose-dependent increase in paw withdrawal threshold compared with pre-administration values and versus the NS group. The concentration of neurokinin-1 receptor was significantly decreased in the Nefopam group (P<0.05). Conclusion: Intraperitoneally administered nefopam yielded a dose-dependent attenuation of mechanical allodynia and decreased neurokinin-1 receptor concentration, suggesting that the neurokinin-1 receptor is involved in the antiallodynic effects of nefopam in vincristine neuropathy.

Improving anti-tumor efficacy of low-dose Vincristine in rhabdomyosarcoma via the combination therapy with FOXM1 inhibitor RCM1

“…Using tumor volumes measured at day 16, we generated a dose response curve to determine the IC 50 concentration for VCR (0.25mg/kg) that later would be used for the combination therapy with RCM1 ( Supplementary Figure S2C ). Since VCR can be toxic ( 5 , 8 , 9 ), the animals were weighed at harvest to compare body weights. There were no differences in body weights between groups, suggesting that these doses of VCR are non-toxic ( Supplementary Figure S2D ).…”

“…Chemotherapy is often used to treat these patients, such as anthracycline-based agents like doxorubicin or epirubicin, alkylating agents like ifosfamide and cyclophosphamide, cytotoxic therapeutics like dactinomycin, and vincristine (VCR), a vinca alkaloid agent ( 6 ). VCR is a cell-cycle specific therapeutic that has been widely accepted as a preferred initial, recurrent, and metastatic treatment for RMS patients ( 2 , 7 , 8 ). Unfortunately, many chemotherapies including VCR are toxic, leading to weight loss, decreased blood counts, and neuropathy ( 2 , 5 , 8 , 9 ).…”

“…VCR is a cell-cycle specific therapeutic that has been widely accepted as a preferred initial, recurrent, and metastatic treatment for RMS patients ( 2 , 7 , 8 ). Unfortunately, many chemotherapies including VCR are toxic, leading to weight loss, decreased blood counts, and neuropathy ( 2 , 5 , 8 , 9 ). VCR is used in combination with other therapeutics to combat toxicity, while also increasing efficacy ( 5 , 7 ).…”

Analgesic Efficacy of Nefopam as an Adjuvant in Patient-Controlled Analgesia for Acute Postoperative Pain After Laparoscopic Colorectal Cancer Surgery

“…Although several analgesic adjuncts to opioid agonists have been studied, including alpha-2 agonist, non-steroidal anti-inflammatory drugs (NSAIDs), and ketamine, it is unclear which combinations are effective [ 10 ]. Nefopam exerts antinociceptive and antihyperalgesic effects by influencing monoamines and the noradrenergic and serotonergic systems, resulting in the reduction and prevention of central sensitization [ 12 , 13 , 14 ]. It has been suggested that the analgesic effect results from reduction in the neurokinin-1 receptor, which may inhibit substance P and neurokinin-1 signaling and subsequently lead to decreased nociceptive responses [ 12 ].…”

“…Nefopam exerts antinociceptive and antihyperalgesic effects by influencing monoamines and the noradrenergic and serotonergic systems, resulting in the reduction and prevention of central sensitization [ 12 , 13 , 14 ]. It has been suggested that the analgesic effect results from reduction in the neurokinin-1 receptor, which may inhibit substance P and neurokinin-1 signaling and subsequently lead to decreased nociceptive responses [ 12 ]. Nefopam has been used in several surgical procedures as an analgesic and as a component of multimodal analgesia for enhanced recovery after surgery (ERAS) [ 15 , 16 , 17 , 18 , 19 ].…”