Additive Effects of Environmental Enrichment and Ketamine on Neuropathic Pain Relief by Reducing Glutamatergic Activation in Spinal Cord Injury in Rats.

Spinal cord injury (SCI) impairs mobility and often results in complications like intractable neuropathic pain. A multi-approach management of this chronic pain condition has been encouraged, but little has been explored of the field. Here, we focus on the effect and underlying mechanism of environmental enrichment (EE), which promotes voluntary social and physical activities, combined with a clinical analgesic, ketamine, on SCI-induced neuropathic pain as well as motor dysfunction. We performed T13 spinal hemisection in rats, which induced unilateral motor impairment and neuropathic pain-like behaviors in the hindlimb. Treatment regimen started a week after SCI, which consists of ketamine administration (30 mg kg-1 day-1; intramuscular) for 10 days, or EE housing for 20 days, or their combination. Paw withdrawal response to mechanical and thermal stimuli, motor function, burrowing behaviors, and body weight was monitored. Spinal segments at T13 lesion and L4-L6 were collected for histopathological and protein analyses. The joint treatment of EE and ketamine provided greater relief of pain-like behaviors and locomotor recovery than did either paradigm alone. These improvements were associated with reduced cavitation area, astrogliosis, and perilesional phosphorylation of glutamate N-methyl-D-aspartate receptor (NMDAR). Concurrently, lumbar spinal analysis of NMDAR-linked excitatory markers in hypersensitization showed reduced activation of NMDAR, mitogen-activated protein kinase (MAPK) family, nuclear factor (NF)-κB, interleukin (IL)-1ß signaling, and restored excitatory amino acid transporter 2 level. Our data support a better therapeutic efficacy of the combination, EE, and ketamine, in the attenuation of neuropathic pain and motor recovery by reducing spinal glutamatergic activation, signifying a potential multifaceted neurorehabilitation strategy to improve SCI patient outcome.

Aberrant Expression of a Proliferation-Inducing Ligand Underlies Autoimmune Mechanisms in Immune Thrombocytopenia.

PURPOSE: To study the relationship between surface membrane-bound APRIL and ITP. METHODS: The peripheral blood of all subjects, 50 patients diagnosed with ITP and 25 healthy controls, was collected. Flow cytometry was used to detect the expression of membrane-bound APRIL on immune cells and platelets. ELISA was used to detect the content of soluble APRIL in plasma. RESULTS: Membrane-bound APRIL was only expressed on the surface of platelets in both ITP patients and controls. APRIL expression on the platelet surface was significantly lower in newly diagnosed (P < 0.001) and chronic (P < 0.001) ITP patients than in controls. Platelet surface APRIL level was significantly enhanced in patients with complete remission after treatment (P = 0.02) but not in those with no response after treatment. Platelet surface APRIL level in ITP patients was negatively correlated with serum APRIL level (r = -0.09765, P = 0.0424). CONCLUSIONS: Platelet surface APRIL may play a key immunoregulative role. Platelet surface APRIL is likely to be one source of the excessive serum APRIL in ITP patients. The effectiveness of treatment may be measured by determining the platelet surface APRIL levels in ITP patients.

Predicting responsiveness to the treatment of rapid ejaculation with 25 mg clomipramine as needed.

Clomipramine (25 mg) taken as needed increases ejaculatory latency in men with rapid ejaculation (RE), although only about half the men treated respond to this regimen. It would therefore be clinically advantageous to know the patient's potential responsiveness to an 'as needed' regimen prior to treatment. The present study attempted to identify a priori factors that might enable prediction of patients' response or nonresponse to 'as needed' clomipramine. Variables relevant to rapid ejaculation were examined in 23 men with RE, 12 of whom had responded to clomipramine. Logistic regression indicated that three factors assessed prior to treatment--initial ejaculation latency, overall sexual satisfaction, and ejaculation frequency each week--significantly improved the prediction of responsiveness to this treatment regimen. Specifically, RE men with initial ejaculatory latencies over 60 s, self-reported sexual satisfaction of 5 or higher (on a seven-point scale), and ejaculation frequency of twice or more weekly were more likely to benefit from 25 mg 'as needed' clomipramine. As such, men meeting these criteria might be considered for this treatment regimen. Those not matching these characteristics might better be considered for 20 or 30 mg clomipramine given on a daily basis.