Roles of Opiate in Lower Urinary Tract Dysfunction Associated With Spinal Cord Injury in Rats

Abstract

These results suggest that the kappa opioid receptor system is related to DSD caused by spinal cord injury. The kappa opioid receptor agent is believed to have therapeutic potential for treating DSD associated with SCI.

Suppression of detrusor-sphincter dysynergia by GABA-receptor activation in the lumbosacral spinal cord in spinal cord-injured rats

“…However, in the chronic phase of spinal cord injury, the bladder exhibits detrusor overactivity, and bladder-sphincter coordination is impaired, leading to detrusor-sphincter dyssynergia (DSD), which is simultaneous contractions of the external urethral sphincter and bladder during the micturition reflex (4). These lower urinary tract dysfunctions then produce various problems, such as urinary incontinence, recurrent urinary tract infection, and vesicoureteral reflux, with or without upper urinary tract deterioration.It has been reported that glutamate, glycine, and opioids can modulate the activity of the external urethral sphincter in the DSD condition (13,15,21). Glutamate is known to be a major excitatory neurotransmitter (18), and both ionotropic N-methyl-D-aspartate and ␣-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid glutamate receptor antagonists inhibit urethral activity in spinal cord injury rats (15).…”

“…It has been reported that glutamate, glycine, and opioids can modulate the activity of the external urethral sphincter in the DSD condition (13,15,21). Glutamate is known to be a major excitatory neurotransmitter (18), and both ionotropic N-methyl-D-aspartate and ␣-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid glutamate receptor antagonists inhibit urethral activity in spinal cord injury rats (15).…”

“…Glycine is a major inhibitory neurotransmitter in the central nervous system, and intrathecal or dietary glycine also inhibits urethral activity in spinal cord injury rats (13). Opioids are also abundant inhibitory neurotransmitters (7), and activation of spinal -opioid receptors selectively depresses the reflex pathways that control external urethral sphincter function in spinal cord injury rats (21).…”

Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury

“…Intrathecal administration of opioid agonists inhibited contractions and reduced DSD in spinal cord injured animal studies and could be used to boost the effects of bladder inhibition with PNS. 140 Lastly, benzodiazepines, acting as an agonist of the effects of GABA A , could enhance the effects of GABA A -mediated PNS bladder inhibition.…”

Prevalence of Opioid-Related Dysuria in Patients With Advanced Cancer Having Pain

“…9 It has been reported that the opioid-receptor system is involved in bladder and urethral function, although the exact mechanism by which opioids cause urinary retention is incompletely understood. 10 Animal and human studies suggest that a significant component of the effect is owing to a combined action on the spinal cord and brain, although peripheral effects at the bladder may also play a role. 8,11 Mechanisms seem to be mediated through central as well as peripheral opioid receptors situated in the spinal cord and in the bladder, respectively.…”