Responsiveness of lumbosacral superficial dorsal horn neurons during the voiding reflex and functional loss of spinal urethral-responsive neurons in streptozotocin-induced diabetic rats.

Abstract

Sensory information from the lower urinary tract (LUT) is conveyed to the spinal cord to trigger and co-ordinate micturition. However, it is not fully understood how spinal dorsal horn neurons are excited during the voiding reflex. In this study, we developed an in vivo technique allowing recording of superficial dorsal horn (SDH) neurons concurrent with intravesical pressure (IVP) during the micturition cycle in both normal and diabetic rats. Lumbosacral dorsal horn neuronal activity and IVP were recorded from urethane-anesthetized naive and streptozotocin (STZ)-induced diabetic rats. Saline was continuously perfused into the urinary bladder through a cannula to induce micturition. We classified SDH neurons into bladder- and urethral-responsive neurons, based on their responsiveness during the voiding reflex. Bladder-responsive SDH neurons responded to the rapid increase in IVP at the start of voiding. In contrast, urethral-responsive SDH neuronal firing increased at the peak IVP and their firing lasted during the voiding phase (the high-frequency oscillations). Urethral-responsive SDH neurons were more sensitive to capsaicin, received C afferent fiber inputs, and were rarely detected in STZ-diabetes rats. Administration of a cyclohexenoic long-chain fatty alcohol (TAC-302), which is reported to promote neurite outgrowth of peripheral nerves in STZ-diabetic rats, prevented the functional loss of spinal urethral response. Sensory information from the bladder and urethra is conveyed separately to different groups of SDH neurons. Functional loss of spinal urethral sensory information through unmyelinated C afferent fibers may contribute to diabetic bladder dysfunction.