Studies On Analgesic Effect Of αO-Conotoxin GeXIVA[1,2] In Chemotherapy Induced Neuropathic Pain

Cancer is a major threat to human health and chemotherapy is one of the most efficient therapy for cancer.However,during cancer treatment,chemotherapy induced neuropathic pain is a common side effect,leading to symptoms like mechanical and cold allodynia,deficit of feeling etc,that severely influence the life quality of patients and could lead to cessation of cancer treatment.Commonly used analgesic drugs behaved poorly in treating this kind of neuropathic pain,there is no available therapy for its treatment.Therefore,it is necessary to develop analgesic drugs with novel mechanisms and cater the unsatisfied clinical needs.Nicotinic acetylcholine receptors(nAChRs)are kind of ligand-gated ion channels widely distributed in the central and peripheral nerve system,and their functions have been proved to be closely related to various neurological diseases like addiction,depression etc.Recently,the a9a 10 nAChRs subtype was confirmed as novel target to treat different neuropathic pain,including pain induced by chemotherapy.In previous researches the analgesic and neuroprotective effect of an a9a 10 nAChRs antagonist,aO-conotoxin GeXIVA[1,2]was discovered in the chronic constriction injury(CCI)model,but whether GeXIVA[1,2]can relieve chemotherapy induced neuropathic pain is unknown.In the present study,we identified the analgesic effect of GeXIVA[1,2]in multiple chemotherapy induced neuropathic pain model,including vincristine,paclitaxel,oxaliplatin induced mice or rat neuropathic pain model.GeXIVA[1,2]was able to attenuate mechanical allodynia in these neuropathic pain models in a dose dependent manner within 6 hours after single intramuscular injection.Moreover,after repeated treatment,GeXIVA[1,2]could reverse cold and mechanical allodynia in oxaliplatin treated rats,the analgesic effect against mechanical allodynia could last for 10 days after termination of a 16 day repeated treatment procedure.GeXIVA[1,2]displays no effect on normal pain perception,body weight and hind limb grip strength after single or repeated injection for 16 days.Therefore,GeXIVA[1,2]could be a novel candidate drug for the treatment of chemotherapy induced neuropathic pain.