New pharmacological approaches against chronic bowel and bladder problems in paralytics

Abstract

Spinal cord injury (SCI) leads generally to an irreversible loss of sensory functions and voluntary motor control below injury level. Cures that could repair SCI and/or restore voluntary walking have not been yet developed nor commercialized. Beyond the well-known loss of walking capabilities, most SCI patients experience also a plethora of motor problems and health concerns including specific bladder and bowel dysfunctions. Indeed, chronic constipation and urinary retention, two significant life-threatening complications, are typically found in patients suffering of traumatic (e.g. , falls or car accidents) or non-traumatic SCI (e.g. , multiple sclerosis, spinal tumors). Secondary health concerns associated with these dysfunctions include hemorrhoids, abdominal distention, altered visceral sensitivity, hydronephrosis, kidney failure, urinary tract infections, sepsis and, in some cases, cardiac arrest. Consequently, individuals with chronic SCI are forced to regularly seek emergency and critical care treatments when some of these conditions occur or become intolerable. Increasing evidence supports the existence of a novel experimental approach that may be capable of preventing the occurrence or severity of bladder and bowel problems. Indeed, recent findings in animal models of SCI have revealed that, despite paraplegia or tetraplegia, it remains possible to elicit episodes of micturition and defecation by acting pharmacologically or electrically upon specialized lumbosacral neuronal networks, namely the spinal or sacral micturition center (SMC) and lumbosacral defecation center (LDC). Daily activation of SMC and LDC neurons could potentially become, new classes of minimally invasive treatments (i.e. , if orally active) against these dysfunctions and their many lifethreatening complications.

The Dual Nature of Onuf’s Nucleus: Neuroanatomical Features and Peculiarities, in Health and Disease

“…Defecatory disorders (e.g., difficulties in defecation, fecal incontinence, and chronic constipation) are common severe problems in SCI patients and are generally attributed to a dysfunctional control of peristalsis and colorectal motility by the CNS (Lynch and Frizelle, 2006 ). In SCI condition, the interactions between the somatic and autonomic components are compromised: indeed, spinal cord trauma leads to a failure of supraspinal inputs modulating the lumbosacral defecation centers and the Onuf’s nucleus, affecting voluntary motor functions and uncoordinated anorectal reflexes (Guertin, 2016 ). In particular, descending fibers from the brainstem lateral cell group make synapses on those Onuf’s MNs that supply the external anal sphincter (Callaghan et al, 2018 ).…”

Normal Distribution and Plasticity of Serotonin Receptors after Spinal Cord Injury and Their Impacts on Motor Outputs

“…A variety of primary and secondary complications occur depending on the severity of the injury and time course of its development. These symptoms may involve different systems, manifesting as, e.g., paralysis, spasticity, neuropathic pain, pulmonary and cardiovascular problems, osteoporosis, anemia, pressure ulcers, bladder and bowel problems, and sexual dysfunction [2][3][4][5][6][7][8]. Currently, there is no cure for SCI and thus improving quality of life, such as restoration of partial motor and sensory functions, has become a priority for setting up the treatment strategy.…”