Compare the Efficacy and Safety of Intranasal Esketamine in Chronic Opioid Refractory Pain

Inclusion Criteria: * Patient with refractory cancer pain, this pain defined when: * Multiple evidence- based biomedical therapies used in a clinically appropriate and acceptable fashion have failed to reach treatment goals that mainly include adequate pain reduction and/or improvement in daily living functioning activities. * Patients' functional activities do not allow a quality of life which is acceptable and/or pharmaceutical therapies have resulted in intolerable adverse effects. * Psychiatric disorders and psychosocial factors that could influence pain outcomes have been assessed and appropriately addressed * Cancer pain classified as chronic (persistent or recurrent pain lasting longer than 3 months), and currently refractory despite optimized analgesic therapy including an opioid. • Optimized analgesic therapy is arbitrarily defined as: oral morphine equivalent of 60 mg/d or more (or another strong opioid at optimized dose) plus at least one adjuvant analgesic drug, for at least 2 weeks. * No increase in baseline long acting opioid dose or addition of a new adjuvant analgesic drug within 2 weeks prior to study entry * Ability to communicate the intensity of pain using the NPRS pain scale ranging from (0 as no pain to 10 with severe pain). * Ability to give fully informed written consent. * Expect survival more than 3 months. Exclusion Criteria: * History of allergy or intolerance to esketamine or ketamine. * History of allergy to disinfecting products containing quaternary ammonium, who might be susceptible to be allergic to denatonium benzoate. * Concomitant use of xanthine derivatives (e.g. aminophylline, theophylline), ergometrine, or monoamine oxidase inhibitors. * Active nasal/sinus dysfunction (e.g. allergic or infectious rhinitis) or presence of any lesion of the nasal mucosa. * Pregnancy, breastfeeding and women of childbearing potential not using a highly effective contraception method. * Uncontrolled hypertension, arrhythmia, heart failure, or untreated coronary artery disease. History of transient ischemic attacks, stroke, neurovascular disease, hemorrhage, severe head injury, hydrocephalus or elevated intracranial pressure within the last 3 months. * History of primary or metastatic malignant brain lesions (uncontrolled or without previous treatment). * Known aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation * Uncontrolled psychiatric illness…