Traumatic spinal cord injury (SCI) has been shown to trigger structural atrophic changes within the spinal cord and brain. However, the relationship between structural changes and magnitude of neuropathic pain (NP) remains incompletely understood. Voxel-wise analysis of anatomical magnetic resonance imaging data provided information on cross-sectional cervical cord area and volumetric brain changes in 30 individuals with chronic traumatic SCI and 31 healthy controls. Participants were clinically assessed including neurological examination and pain questionnaire. Compared to controls, individuals with SCI exhibited decreased cord area, reduced grey matter (GM) volumes in anterior cingulate cortex (ACC), left insula, left secondary somatosensory cortex, bilateral thalamus, and decreased white matter volumes in pyramids and left internal capsule. The presence of NP was related with smaller cord area, increased GM in left ACC and right M1, and decreased GM in right primary somatosensory cortex and thalamus. Greater GM volume in M1 was associated with amount of NP. Below-level NP-associated structural changes in the spinal cord and brain can be discerned from trauma-induced consequences of SCI. The directionality of these relationships reveals specific changes across the neuroaxis (i.e., atrophic changes versus increases in volume) and may provide substrates of underlying neural mechanisms in the development of NP.

Adenosine triphosphate (ATP) is a signaling molecule that regulates cellular processes. Based on previous studies of bladder function over the past decade, bladder ATP signaling was thought to have an essential role in the normal micturition reflex. In this study, we performed detailed analyses of bladder function in purinergic receptor-deficient mice using the automated voided stain on paper method and video-urodynamics. Unexpectedly, a lack of P2X2 or P2X3 receptors did not affect bladder function under normal physiological conditions, indicating that bladder ATP signaling is not essential for normal micturition reflex. In contrast, we found that lipopolysaccharide (LPS) induced markedly high levels of ATP release from the urothelium. In addition, LPS-induced rapid bladder hyperactivity was attenuated in P2X2(-/-) and P2X3(-/-) mice. Contrary to the previous interpretation, our present findings indicate that bladder ATP signaling has a fundamental role in the micturition reflex, especially in bladder dysfunction, under pathological conditions. Therefore, the bladder ATP signaling pathway might be a highly promising therapeutic target for functional bladder disorders. This study newly defines an authentic role for bladder ATP signaling in the micturition reflex.

A balance between stiffness and compliance is essential to normal bladder function, and changes in the mechanical properties of the bladder wall occur in many bladder pathologies. These changes are often associated with the release of basic secretagogues that in turn drive the release of inflammatory mediators from mast cells. Mast cell degranulation by basic secretagogues is thought to occur by activating an orphan receptor, Mas-related G protein-coupled receptor B2 (Mrgprb2). We explored the effects of the putative mast cell degranulator and Mrgprb2 agonist Compound 48/80 on urinary bladder wall mechanical compliance, smooth muscle contractility, and urodynamics, and if these effects were mast cell dependent. In wild-type mice, Mrgprb2 receptor mRNA was expressed in both the urothelium and smooth muscle layers. Intravesical instillation of Compound 48/80 decreased intermicturition interval and void volume, indicative of bladder overactivity. Compound 48/80 also increased bladder compliance while simultaneously increasing the amplitude and leading slope of transient pressure events during ex vivo filling and these effects were inhibited by the Mrgprb2 antagonist QWF. Surprisingly, all effects of Compound 48/80 persisted in mast cell-deficient mice, suggesting these effects were independent of mast cells. These findings suggest that Compound 48/80 degrades extracellular matrix and increases urinary bladder smooth muscle excitability through activation of Mrgprb2 receptors located outside of mast cells. Thus, the pharmacology and physiology of Mrgprb2 in the urinary bladder is of potential interest and importance in terms of treating lower urinary tract dysfunction.

Q-tip test offers a simple approach for identifying urethral hypermobility. Considering surgical treatment, stress urinary incontinence (SUI) must be classified and the contribution of intrinsic sphincter deficiency (ISD) and/or urethral hypermobility must be determine. We believe there's a correlation between abdominal leak point pressure (ALPP) and urethral mobility degree, and the aim of this study is to explore it using Q-tip. We conducted a prospective study, between years 2014 and 2016. Females over 18 years presenting with signs and symptoms of SUI according to the 2002 ICS Standardization of Terminology were included. Assessment was made with the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), the Q-tip test and invasive urodynamics. Urethral mobility (UM) and ALPP were analyzed. We built two composite variables based on reported risk factors for ISD, defined as composite variable A (equal to a Q-tip test < 30° AND ICIQ-SF ≥ 10 points) and composite variable B (equal to low urethral mobility AND/OR hypoestrogenism AND/OR history of radiotherapy AND/OR previous pelvic surgery). Correlation analyzes were made according to the type of variable. A total of 221 patients were included. Incontinence was rated as moderate and severe by 65.3% and 6.8%, respectively. The analysis showed a 61.75%, 51.61% and 70.6% agreement between ALPP and UM, ALPP and composite variable A and ALPP and composite variable B respectively. Correlation and concordances were low (r = 0.155, r_s = - 0.053 and r_s = - 0.008), (rho_c = 0.036, k = 0.116 and k = 0.016). Neither the degree of UM, nor the composite variables, correlate or agree with urethral function tests in UDS, suggesting that the ALPP cannot be predicted using the Q-tip test or the ICIQ-SF for classifying patients with SUI.