Pharmacological Evaluation of Morphine and Non-opioid Analgesic Adjuvants in a Mouse Model of Skin Cancer Pain

Abstract

Using a mouse model of advanced skin cancer which has mixed nociceptive-neuropathic pain, we evaluated the analgesic effects of morphine and analgesic adjuvants. Morphine hydrochloride (10--30 mg/kg, oral) and mexiletine hydrochloride (10--30 mg/kg, intraperitoneal) dose-dependently inhibited thermal hyperalgesia. Baclofen (10 mg/kg, subcutaneous) suppressed thermal hyperalgesia, without effects at lower doses of 1 and 5 mg/kg. Ketamine hydrochloride (50 mg/kg, oral) was without effect. Analgesic tolerance was observed after 6th administration of morphine, and it was not developed until at least 7th administration of mexiletine and baclofen. This mouse model of skin cancer may be useful for the pharmacological evaluation of the effects of opioids and analgesic adjuvants on mixed nociceptive-neuropathic pain of advanced cancer.