A Compound Mitigates Cancer Pain and Chemotherapy-Induced Neuropathic Pain by Dually Targeting nNOS-PSD-95 Interaction and GABAA Receptor.

Metastatic bone pain and chemotherapy-induced peripheral neuropathic pain are the most common clinical symptoms in cancer patients. The current clinical management of these two disorders is ineffective and/or produces severe side effects. The present study employed a dual-target compound named as ZL006-05 and examined the effect of systemic administration of ZL006-05 on RM-1-induced bone cancer pain and paclitaxel-induced neuropathic pain. Intravenous injection of ZL006-05 dose-dependently alleviated RM-1-induced mechanical allodynia, heat hyperalgesia, cold hyperalgesia, and spontaneously ongoing nociceptive responses during both induction and maintenance periods, without analgesic tolerance, affecting basal/acute pain and locomotor function. Similar behavioral results were observed in paclitaxel-induced neuropathic pain. This injection also decreased neuronal and astrocyte hyperactivities in the lumbar dorsal horn after RM-1 tibial inoculation or paclitaxel intraperitoneal injection. Mechanistically, intravenous injection of ZL006-05 potentiated the GABAA receptor agonist-evoked currents in the neurons of the dorsal horn and anterior cingulate cortex and also blocked the paclitaxel-induced increase in postsynaptic density-95-neuronal nitric oxide synthase interaction in dorsal horn. Our findings strongly suggest that ZL006-05 may be a new candidate for the management of cancer pain and chemotherapy-induced peripheral neuropathic pain.

Outpatient Interventions That May Enhance the Care of a Patient with Co-existing Moyamoya and Down Syndromes.

Moyamoya vasculopathy is a condition of chronic, progressive occlusion of the distal internal carotid arteries and the Circle of Willis. The resultant ischemia produces compensatory angiogenesis and the growth of a network of collateral blood vessels, which on angiography resemble a "puff of smoke" or "moyamoya" in Japanese. The objective of this case report is to describe the clinical course of a patient with Down and moyamoya syndromes and to enlighten clinicians about strategies that can be taken to enhance the care of similar patients. A 55-year-old African American female presented to the hospital with complaints of headache, vision loss, dysarthria, and ataxia. She had a past medical history of Down syndrome and a stroke with residual lower extremity weakness. At her baseline, the patient was able to perform her activities of daily living but required assistance with independent activities of daily living. Computed tomography of the brain showed hypodense areas at the right occipital, temporal, and parietal lobes. Computed tomography angiography of the head and neck identified occlusion bilaterally at the supraclinoid internal carotid arteries and right posterior cerebral artery; there was collateral arterial flow within the right middle cerebral and anterior cerebral arteries that was consistent with moyamoya vasculopathy. Patients with Down syndrome experience premature accelerated aging and suffer from comorbidities seen in geriatric patients by the time they reach their 40s. Patients with moyamoya vasculopathy experience neurocognitive and neuropsychiatric deficits that correspond to the regions of the brain that are affected. This patient with Down and moyamoya syndromes had impaired neurocognitive and functional status, and we believe that she would have benefited from receiving a comprehensive geriatric assessment and neuropsychiatric testing.