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We present a multimodal method combining quantitative electroencephalography (EEG), behavior and pharmacology for pre-clinical screening of analgesic efficacy in vivo. The method consists of an objective and non-invasive approach for realtime assessment of spontaneous nociceptive states based on EEG recordings of theta power over primary somatosensory cortex in awake rats. Three drugs were chosen: (1) pregabalin, a CNS-acting calcium channel inhibitor; (2) EMA 401, a PNS-acting angiotensin II type 2 receptor inhibitor; and (3) minocycline, a CNS-acting glial inhibitor. Optimal doses were determined based on pharmacokinetic studies and/or published data. The effects of these drugs at single or multiple doses were tested on the attenuation of theta power and paw withdrawal latency (PWL) in a rat model of neuropathic pain. We report mostly parallel trends in the reversal of theta power and PWL in response to administration of pregabalin and EMA 401, but not minocycline. We also note divergent trends at non-optimal doses and following prolonged drug administration, suggesting that EEG theta power can be used to detect false positive and false negative outcomes of the withdrawal reflex behavior, and yielding novel insights into the analgesic effects of these drugs on spontaneous nociceptive states in rats.

the circadian clock programs daily rhythms and coordinates multiple behavioural processes, including micturition. partial bladder outlet obstruction (pBoo) in mice produces hyperactive voiding. However, long-term effects of pBOO on bladder function have not been clarified. In this study, we investigated micturition under conditions of impaired circadian bladder function by inducing long-term pBoo by tying the proximal urethra. Micturition behavior was evaluated at 1, 3, 6 and 12 months after surgery. We used automated voided stain on paper method for a precise micturition recording for mice. And quantitative assessment of gene expression was performed at 24 months after pBOO surgery using qRT-PCR procedure. The micturition frequencies in the pBOO group were significantly decreased at 3, 6, and 12 months compared to those at 1 month after operation in the same group (p < 0.05). Body weight of pBOO mice was significantly increased compared to sham operated mice at 12 months. The expression level of mRNA was exhibited a 3.4-fold nominal increased for a 5-HT2B receptor in the pBoo group compared to the sham group. the current study found that long-term pBoo led to disruption of the circadian bladder function (the day/night cycle) in mice, similar to those observed in human as nocturia. this disruption is possible involvement of the gain of body weight and/or serotonergic alteration after pBoo. Abbreviations BOO Bladder outlet obstruction pBOO Partial bladder outlet obstruction LUTS Lower urinary tract symptoms aVSOP Automated voided stain on paper Mets Metabolic syndrome CRF Corticotropin-releasing factor HPA Hypothalamus-pituitary-adrenal α1ARs α1-Adrenergic receptors In men as a result of benign prostatic enlargement bladder outlet obstruction (BOO) is one of the most common causes of lower urinary tract symptoms (LUTS). Partial BOO (pBOO) significantly alters bladder morphology and function. Clinically, benign prostatic hyperplasia, bladder neck sclerosis, urethral valves or urethral strictures can cause mechanical BOO 1. Although a correlation between LUTS and BOO or metabolic syndrome are known, to our knowledge, the detailed aetiology of LUTS remains unknown. Some symptoms, e.g. nocturia, remain to treat completely due to unclear mechanisms of LUTS. Several studies have shown that nocturia is a common complaint and (one of) the most frequent events in male LUTS. Nocturnal voiding disrupts sleep, and therefore repeated nocturnal voiding deteriorates the health-related quality of life 2. There is very little information about the micturition behaviour as circadian bladder function in animal model. Previous studies have shown that pBOO induces non-voiding contraction and shortening of inter-contraction interval in urinary bladder in animals 3,4. Furthermore, pBOO leads to several morphological and functional changes in afferent pathways as well as in the bladder. To empty partial obstructed-bladder, pBOO produces compensate hypertrophy of detrusor, which causes gain of the thickness and weight of the bladder wall ...

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