The NLRP3/IL-1β-mediated inflammation pathway plays a significant role in denervation during BOO.

PurposeDiabetes is a grave and progressive condition characterized by debilitating complications. Diabetic bladder dysfunction (DBD) is a very common complication with no specific treatments currently available. Unlike other tissues affected by this disease, the bladder is subjected to two independent insults; 1) polyuria, created by the osmotic effects of glucose in the urine, and 2) hyperglycemia itself. Based on our understanding of inflammation as a major contributor to the underlying organ damage in several other diabetic complications, its presence in the bladder during DBD and the contribution of polyuria and hyperglycemia to its development were assessed.MethodsAwake, restrained cystometry was performed on wild type C57BL/6 mice and diabetic (Akita) mice on a C57BL/6 background at 15 weeks of age. A subgroup of the Akita mice were treated with phlorizin, an inhibitor of sodium-glucose linked transporter types 1 and 2 that prevents glucose reabsorption in the kidney. All groups were assessed for serum glucose, 4-hour voiding totals, and inflammation in the bladder (Evans blue assay).ResultsAkita mice develop cystometrically-defined DBD by 15 weeks of age, as evidenced by an increase in urinary frequency, a decrease in voiding volume, and an increase in post-voiding residual volume. Phlorizin effectively normalized serum glucose in these animals while increasing the urine output. Inflammation in the bladder was present in the diabetic animals at this time point, but not detectable in animals receiving phlorizin.ConclusionInflammation in the bladder of diabetic mice correlates with the development of DBD and is triggered by hyperglycemia, not polyuria.

Neuropathic pain following spinal cord injury involves plastic changes along the whole neuroaxis. Current neuroimaging studies have identified grey matter volume (GMV) and resting-state functional connectivity changes of pain processing regions related to neuropathic pain intensity in spinal cord injury subjects. However, the relationship between the underlying neural processes and pain extent, a complementary characteristic of neuropathic pain, is unknown. We therefore aimed to reveal the neural markers of widespread neuropathic pain in spinal cord injury subjects and hypothesized that those with greater pain extent will show higher GMV and stronger connectivity within pain related regions. Thus, 29 chronic paraplegic subjects and 25 healthy controls underwent clinical and electrophysiological examinations combined with neuroimaging. Paraplegics were demarcated based on neuropathic pain and were thoroughly matched demographically. Our findings indicate that (a) spinal cord injury subjects with neuropathic pain display stronger connectivity between prefrontal cortices and regions involved with sensory integration and multimodal processing, (b) greater neuropathic pain extent, is associated with stronger connectivity between the posterior insular cortex and thalamic sub-regions which partake in the lateral pain system and (c) greater intensity of neuropathic pain is related to stronger connectivity of regions involved with multimodal integration and the affective-motivational component of pain. Overall, this study provides neuroimaging evidence that the pain phenotype of spinal cord injury subjects is related to the underlying function of their resting brain.

Study design Clinimetric cross-sectional cohort study in adults with paraplegic spinal cord injury (SCI) and neuropathic pain (NP). Objective To assess the reliability of standardized quantitative pain drawings in patients with NP following SCI. Setting Hospital-based research facility at the Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland. Methods Twenty individuals with chronic thoracic spinal cord injury and neuropathic pain were recruited from a national and local SCI registry. A thorough clinical examination and pain assessments were performed. Pain drawings were acquired at subsequent timepoints, 13 days (IQR 7.8–14.8) apart, in order to assess test-retest reliability. Results The average extent [%] and intensity [NRS 0–10] of spontaneous NP were 11.3% (IQR 4.9–35.8) and 5 (IQR 3–7), respectively. Pain extent showed excellent inter-session reliability (intraclass correlation coefficient 0.96). Sensory loss quantified by light touch and pinprick sensation was associated with larger pain extent (rpinprick = −0.47, p = 0.04; rlight touch = −0.64, p < 0.01). Conclusion Assessing pain extent using quantitative pain drawings is readily feasible and reliable in human SCI. Relating information of sensory deficits to the presence of pain may provide distinct insights into the interaction of sensory deafferentation and the development of neuropathic pain after SCI.

The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions, i.e., residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared to objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively).Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%) and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relation was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%).In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discern STT lesion completeness might support revealing the interference with neuropathic pain following SCI.

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