Neuropathic pain Chemotherapy-induced peripheral neuropathy (CIPN)

Background information: Repeated administration in rodents of commonly used chemotherapeutic agents, such as platinum derivatives and vinca alkaloids, reproduces many of the pathological mechanisms associated with human CIPN, supporting the utility of these experimental models for mechanistic studies of peripheral neuropathy induced chemotherapy treatment and for the screening of novel analgesic compounds. CIPN is manifested in rodents by robust and long-lasting referred pain (hypersensitivity to acute application of noxious (hyperalgesia) and non-noxious (allodynia) stimuli in the animal hind paws.

Animals: SD rats (vincristine model), Wistar rats (oxaliplatin model).

Efficacy test: The efficacy of systemic administered drugs can be evaluated after acute administration during the period of stable allodynia (approximately during 1 or 2 weeks after finishing the administration of chemotherapeutic agent) (acute analgesic effect), or after repeated treatment in a preventive protocol (disease-modifying effect). Efficacy evaluation of drug combinations is also possible, including isobolographic analysis of the interaction.

Assessments: Mechanical allodynia is evaluated by measuring hind paw withdrawal threshold (g) in response to mechanical (von Frey test) stimulation. Additional readouts can also be evaluated (i.e., cold allodynia) (not validated).

Positive control: Pregabalin (acute analgesic efficacy)

Criteria for significance: ANOVA followed by Tukey’s test is applied for comparison between the vehicle and treatment groups. Significant activity is considered at the P<0.05 level.

Turnaround time: xx Days.