Effects of cannabidiol or morphine on mechanical sensitivity and place conditioning induced by chemotherapy‐induced peripheral neuropathy in mice

Abstract

Paclitaxel is a chemotherapeutic agent commonly associated with chemotherapy‐induced peripheral neuropathy (CIPN). We have recently shown that the phytocannabinoid cannabidiol (CBD) can prevent the development of paclitaxel‐induced mechanical allodynia in female C57Bl/6 mice. In the present set of studies, we assessed acute effects of morphine (2.5–10 mg/kg) and CBD (2.5–10 mg/kg) in reversing paclitaxel‐induced neuropathic pain using two assays: i) traditional stimulus‐evoked mechanical allodynia; and ii) non‐traditional place‐conditioning assays to measure non‐evoked affective components of neuropathic pain. Results showed dose‐dependent reversal of paclitaxel‐induced mechanical allodynia by morphine and significant reversal by CBD at all the three doses tested. We then studied the effects of paclitaxel on CBD (2.5–10 mg/kg) and morphine (2.5–10 mg/kg)‐induced place conditioning. Results showed that CBD produced significant place‐preference only in mice that were in the paclitaxel‐induced pain state, while morphine was rewarding in both naïve mice and mice experiencing neuropathic pain. Taken together, these results demonstrate that CBD unlike morphine is effective at relieving chemotherapy‐induced neuropathic pain with no associated psycho‐active effects. These assays also support the clinical observation that opioids are not effective in the treatment of neuropathic pain.