Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24-q31, a region known to contain a cluster of voltage-gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7. The mutations completely co-segregated with the disease phenotype, and nine of these SCN9A mutations resulted in truncation and loss-of-function of the Nav1.7 channel. These genetic data further support the evidence that Nav1.7 plays an essential role in mediating pain in humans, and that SCN9A mutations identified in multiple different populations underlie CIP.

No abstract

These results suggest an objective acute effect of posterior tibial nerve stimulation on urodynamic parameters. Improved bladder overactivity is an encouraging argument to propose posterior tibial nerve stimulation as a noninvasive treatment modality in clinical practice.

Urinary incontinence is a frequent affliction in women and may be disabling and costly {LE1}. When consulting for urinary incontinence, it is recommended that circumstances, frequency and severity of leaks be specified {Grade B}. The cough test is recommended prior to surgery {Grade C}. Urodynamic investigations are not needed before lower urinary tract rehabilitation {Grade B}. A complete urodynamic investigation is recommended prior to surgery for urinary incontinence {Grade C}. In cases of pure stress urinary incontinence, urodynamic investigations are not essential prior to surgery provided the clinical assessment is fully comprehensive (standardised questionnaire, cough test, bladder diary, post-void residual volume) with concordant results {PC}. It is recommended to start treatment for stress incontinence with pelvic floor muscle training {Grade C}. Bladder training is recommended at first intention in cases with overactive bladder syndrome {Grade C}. For overweight patients, loss of weight improves stress incontinence {LE1}. For surgery, sub-urethral tape (retropubic or transobturator route) is the first-line recommended technique {Grade B}. Sub-urethral tape surgery involves intraoperative risks, postoperative risks and a risk of failure which must be the subject of prior information {Grade A}. Elective caesarean section and systematic episiotomy are not recommended methods of prevention for urinary incontinence {Grade B}. Pelvic floor muscle training is the treatment of first intention for pre- and postnatal urinary incontinence {Grade A}. Prior to any treatment for an elderly woman, it is recommended to screen for urinary infection using a test strip, ask for a bladder diary and measure post-void residual volume {Grade C}. It is recommended to carry out a cough test and look for occult incontinence prior to surgery for pelvic organ prolapse {Grade C}. It is recommended to carry out urodynamic investigations prior to pelvic organ prolapse surgery when there are urinary symptoms or occult urinary incontinence {Grade C}.