Neurology and Neuropharmacology of Normal and Abnormal Urination

CHAPTER 16
Neurology and Neuropharmacology of Normal and Abnormal Urination


Curtis W. Dewey & Ronaldo C. da Costa


Introduction20, 27


Disorders of urination are commonly encountered in patients with neurologic disease. If not properly managed, they can become more of a health concern than the underlying neurologic disorder. Serious urinary tract problems (e.g. atonic bladder, pyelonephritis) that are secondary to neurologic disease are usually preventable. The key to prevention is a combination of having a sound knowledge base and being a careful examiner. It should never be assumed that a paralyzed dog or cat is urinating adequately because someone saw a pool of urine in that patient’s cage. This should always be verified (e.g. palpate the bladder, observe for voluntary urination). It is essential that the clinician understands how to deal with what is commonly referred to as the “neurologic bladder.” The techniques of bladder expression and urethral catheterization are discussed in Chapter 20. This chapter focuses on the functional neuroanatomy and neuropharmacology of urination. The basic principles outlined in this chapter are necessary for the clinician to understand what type of bladder dysfunction is present (e.g. upper motor neuron [UMN] or lower motor neuron [LMN] bladder) and what drugs are likely to help in managing the dysfunction.


Functional neuroanatomy of the urinary bladder and urethra (Fig. 16.1 and Fig. 16.2)1, 8, 9, 11–13, 16, 20, 22, 26, 27, 29, 33, 36

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Figure 16.1 Schematic illustration depicting the location of receptor types on the bladder wall and urethra. (The Ohio State University. Reproduced with permission.)

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Figure 16.2 Schematic illustration depicting the neuroanatomy and neurophysiology of urination. L1–L4 = lumbar spinal cord segments. S1–S3 = sacral spinal cord segments. (The Ohio State University. Reproduced with permission.)



  1. The urinary bladder

    1. The urinary bladder is a hollow organ primarily composed of three layers of smooth muscle, collectively termed the detrusor muscle. There are also mucosal, submucosal, and serosal layers. The detrusor muscle contains both adrenergic and cholinergic (muscarinic) receptors that are important in bladder filling and contraction, respectively. The important receptors for efferent autonomic innervation of the body of the bladder are summarized below:

      1. Beta-adrenergic receptors—these sympathetic receptors are innervated by the hypogastric nerve, which in turn originates from the L1–L4 spinal cord segments in the dog (L2–L5 segments in the cat). Stimulation of these receptors causes detrusor muscle relaxation, which allows bladder filling.
      2. Muscarinic cholinergic receptors—these parasympathetic receptors are innervated by the pelvic nerve, which originates from the sacral (S1–S3) spinal cord segments. Stimulation of these receptors causes detrusor muscle contraction, which leads to bladder emptying.

    2. There are also sensory receptors (stretch and pain) in the wall of the bladder. Stretch receptors are innervated by afferent axons that travel through the pelvic nerve toward the sacral spinal cord segments. Pain receptors are innervated by afferent axons that travel in both the pelvic and hypogastric nerves, but primarily in the hypogastric nerves.

  2. The urethra

    1. For practical purposes, the neck of the bladder can be thought of as the proximal aspect of the urethra. The smooth muscle of the urethra is primarily innervated by the hypogastric nerve and is often considered to represent an internal sphincter, although it is not a true sphincter. The external urethral sphincter is composed of striated muscle that encircles the distal urethra. The external urethral sphincter is innervated by the pudendal nerve. This is a somatic motor nerve whose cell bodies are in the sacral spinal cord segments (primarily S1 and S2). The important receptors for efferent urethral innervation are as follows:

      1. Alpha-adrenergic receptors—these sympathetic receptors are innervated by the hypogastric nerve. Stimulation of these receptors causes contraction of smooth muscle in the neck of the bladder and urethra. This muscle contraction opposes urine flow through the urethra, and therefore facilitates bladder filling.
      2. Nicotinic cholinergic receptors—these somatic motor receptors are located on the external urethral sphincter and are innervated by the pudendal nerve. The pudendal nerve is under voluntary control, but the neuronal cell bodies of this nerve within the sacral spinal cord also receive involuntary afferent input. Stimulation of these receptors causes sphincter contraction, which opposes urine flow through the urethra, thus facilitating bladder filling.

    2. Similar to the bladder, there are sensory receptors in the wall of the urethra for conveying information concerning distention (stretch), pain, and urine flow. These receptors are innervated by afferent axons that travel in the pudendal nerve toward the sacral spinal cord segments.

Local reflex arcs8, 9, 11, 13, 16, 20, 22, 25–27, 29, 33, 36



  1. Somewhat analogous to innervation of the limbs, there are inherent spinal reflex arcs involved in bladder filling and emptying. Although there is some level of spinal reflex control of urination in adult dogs and cats, these reflex arcs cease to function autonomously after infancy (3–4 wks in puppies, 7–12 wks in kittens). Thereafter, these reflex centers require descending influences from the brain stem for coordinated urination to occur. The reflex arcs depend on a number of anatomic structures:

    1. The pelvic plexus—this refers to the meshwork of autonomic nerves and ganglia located in the pelvic canal. Within this plexus are afferent and efferent processes of the pelvic and hypogastric nerves.
    2. The pudendal nerve—technically part of the lumbosacral plexus, this nerve is also located in the pelvic canal.
    3. The sacral spinal cord—neuronal cell bodies for the pelvic nerve are located in the intermediolateral gray matter, and neuronal cell bodies for the pudendal nerve are located in the ventral horn gray matter.
    4. The lumbar spinal cord—neuronal cell bodies for the hypogastric nerve are located in the intermediolateral gray matter from L1–L4 spinal cord segments in the dog and L2–L5 segments in the cat.

  2. As the bladder fills, stretch receptors are stimulated and this afferent information is carried via the pelvic nerve to the parasympathetic nuclei in the sacral spinal cord. Efferent impulses from these nuclei through the pelvic nerve initiate detrusor contraction. As the detrusor muscle contracts, another volley of afferent impulses enters the sacral spinal cord. Some of these afferent axons inhibit the sacral neuronal cell bodies of the pudendal nerve, whereas some ascend to the lumbar spinal cord to inhibit the sympathetic cell bodies of the hypogastric nerve. The net result is bladder contraction with nearly simultaneous urethral relaxation and coordinated urination.

The brain-stem micturition center and the detrusor reflex4, 5, 8, 9, 11, 13, 14, 18, 22, 23, 26, 27, 29, 31, 33, 36




  1. The brain-stem micturition center


    Neuronal populations in the brain stem normally coordinate the spinal reflex arcs involved in bladder filling and emptying. These neurons are principally located in the reticular formation of the pons, and to a lesser degree in the midbrain and medulla. Two distinct regions of the pons have been demonstrated to be involved in the filling and evacuation phases of the detrusor reflex, respectively. The dorsolateral region of the pons contains two groups of neurons involved in the micturition reflex: a medial cell group (M region) and a lateral cell group (L region). Neurons of the M region (Barrington’s nucleus) project excitatory axons to the parasympathetic (muscarinic cholinergic) motor neurons in the sacral spinal cord that give rise to the pelvic nerves. Axonal processes from M region neurons also innervate inhibitory interneurons (GABA-ergic) that synapse on nicotinic cholinergic motor neurons in the sacral spinal cord that give rise to the pudendal nerves. Activation of neurons of the M region facilitates urinary bladder evacuation.


    Axons projecting from the L region neurons have excitatory synaptic connections with nicotinic cholinergic sacral motor neurons that give rise to the pudendal nerves. Activation of L region neurons facilitates urinary bladder filling. The brain-stem micturition center can be considered the UMN for normal urination.



  2. The detrusor reflex


    Some of the afferent impulses (from stretch receptors) from the bladder and urethra are conveyed rostrally up the spinal cord (via spinothalamic pathways) to the brain-stem micturition center, rather than terminating on spinal cord neuronal pools. Neurons of the brain-stem micturition center subsequently convey descending efferent information through the spinal cord (reticulospinal tracts, tectospinal tracts) to the various spinal cord neuronal pools involved in urination. The coordinated act of urination that results from completing this brain-stem/spinal cord reflex arc is referred to as the detrusor reflex. It should be kept in mind that this is a brain-stem reflex that does not require conscious input (cerebral cortical influence) to operate.


Forebrain and cerebellar influence on the detrusor reflex4, 5, 8, 9, 11, 13, 14, 17, 20–22, 26, 27, 29, 35




  1. Forebrain influence


    Afferent impulses from the bladder reach the cerebral cortex via the pelvic (cat) and hypogastric (dog and cat) nerves and ascending spinal cord tracts. The sensations of stretch and pain are conveyed to the cerebral cortex via these afferent pathways. The detrusor reflex can be consciously inhibited via the cerebral cortex; this is the basis of house-training. The detrusor reflex can also be voluntarily initiated (e.g. territorial marking behavior). Patients with cerebral cortical dysfunction typically urinate normally, but will do so in inappropriate locations (loss of learned urination habits). The basal nuclei and preoptic area of the hypothalamus may play a role in the initiation of bladder evacuation. The ventromedial region of the hypothalamus has an inhibitory influence on urination.



  2. Cerebellar influence


    The influence of the cerebellum on urination appears to be minor. The cerebellum normally exerts an inhibitory influence over the detrusor reflex. Cerebellar lesions may result in increased frequency of urination.


Normal bladder filling and evacuation1, 4, 5, 8, 9, 11, 13, 14, 16, 20, 22, 23, 25–27, 29, 31, 33, 36



  1. Bladder filling (primarily controlled by L region of the pons; Fig. 16.3

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Apr 7, 2020 | Posted by in SMALL ANIMAL | Comments Off on Neurology and Neuropharmacology of Normal and Abnormal Urination

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