Cannabidiol prevents the development of allodynia in paclitaxel‐treated female C57Bl6 mice

Paclitaxel (PAC) is associated with a chemotherapy‐induced neuropathic pain (CINP) state that can lead to the cessation of treatment in late stage breast cancer patients, even in the absence of alternate therapies. Rodent models of CINP‐associated allodynia following systemic dosing of PAC are used to investigate underlying mechanisms and potential treatments, but studies are largely restricted to male rats, while well‐characterized effects of CINP in female mice are lacking. In the present set of experiments, we investigated the effect of a wide range of repeated PAC doses (1.0 – 8.0 × 4 inj IP) on cold (acetone drop test) and mechanical (Von Frey test) allodynia in male and female C57Bl/6 mice. Because the non‐psychoactive Cannabis constituent cannabidiol (CBD) has been shown to attenuate other forms of neuropathic pain, we also assessed the effect of CBD (5.0–10.0 mg/kg IP) on PAC‐induced allodynia in the female mice. Treatment with PAC produced both cold and mechanical allodynia in male and female mice. These effects were largely dose‐independent, with some effects larger in females versus males. Both doses of CBD prevented the development of PAC‐induced cold and mechanical allodynia, and these effects were statistically significant from PAC alone. Therefore, adjunct treatment with CBD during chemotherapy treatment with PAC may be effective in the prevention or attenuation of CINP. (Supported by R01 CA129092)