Intravesical capsaicin for treatment of detrusor hyperreflexia.

Abstract

An intravesical instillation of 100 ml 1 or 2 mmolIl capsaicin has been used to treat detrusor hyperreflexia giving rise to intractable urinary incontinence in 12 patients with spinal cord disease and two other patients with detrusor overactivity of non-spinal origin. Nine patients, all of whom had spinal cord disease, showed some improvement in bladder function. The benefit was only shortlived and partial in four, but the remaining five achieved complete continence while performing intermittent self catheterisation. Urodynamic studies in these nine patients showed an increase in mean (SD) bladder capacity from 106 (57) to 302 (212) ml and a fall in the maximum detrusor pressure from 54 (20) Detrusor hyperreflexia can result either from loss of the normal inhibitory input from higher centres on to the pontine micturition centre or after a spinal lesion from interruption of the spinobulbospinal pathways that normally control physiological bladder behaviour. Animal models of chronic spinal cord disease have shown that after disruption of the connections between the pons and the sacral spinal cord a new segmental sacral reflex arc becomes functional.' The afferent neurones of this emergent reflex in the cat are mostly unmyelinated C fibres whereas in the neurologically intact animal afferent neurones from the bladder are small myelinated A5 fibres.2 Little is known of the neurological mechanism of bladder reflexes in spinally injured humans.' Disconnection of the sacral cord from the pons results in detrusor areflexia that lasts for about six weeks before volume determined bladder reflex emptying becomes established. A speculative hypothesis is that this change in detrusor behaviour results from synaptic reorganisation and possibly new nerve growth forming the neurological basis of an emerging reflex arc.Pharmacological experiments show that in many species there is a large group of fibres innervating the bladder that are capsaicin sensitive.3-6 These are mostly unmyelinated fibres in the cat' and rat.7 They are silent under physiological conditions but may be activated by bacterial or chemical irritants in the bladdere giving rise to symptoms of cystitis. It is probably these same fibres that emerge active and serve as the afferent arc for detrusor hyperreflexia in spinally injured animals. ' Capsaicin activates a vanilloid receptor on the cell membrane of sensitive primary sensory neurones9 causing an increase in cation permeability and leading to membrane depolarisation. Activation of the vanilloid receptor produces a biphasic response. The immediate effect is stimulatory with transmission of sensory impulses from the periphery to the central nervous system sensed as a painful irritation and a peripheral release from the receptor terminals of neuropeptides including substance P and CGRP. After exposure to high concentrations of capsaicin, afferent C fibres may show long lasting functional

The effects of capsaicin on the neurogenic hyperreflexic detrusor. A double blind placebo controlled study in patients with spinal cord disease. Preliminary results

“…5 An improvement of 140 ml in the bladder capacity should, for a mean hourly diuresis of 50 to 100 ml, result in an increase in the intervoiding period of 1.5 to 3 h. This corresponds quite closely with the reduction in voiding frequency found in our trial.…”

“…The installation protocol used in our study was strictly that described by Fowler. 5 We obtained detailed data on side e ects (Table 4) which were present in almost every patient at the time of the installation (suprapubic burning sensation, sensory urgency, hot¯ush and, more rarely, autonomic hyperre¯exia) as well as within the following 6 days (suprapubic burning sensation, exacerbation of incontinence, macroscopic hematuria). These e ects were also reported by the previous authors, who considered them to be clinically tolerable, as did we.…”

Intravesical Capsaicin Versus Resiniferatoxin In Patients With Detrusor Hyperreflexia: A Prospective Randomized Study

“…9 Does lidocaine attenuate the potential benefits of capsaicin? We consider this hypothesis most unlikely because capsaicin causes excitation (nociception) and then desensitization through nonselective receptor mediated ion channels, whereas lidocaine blocks axonal transmission through voltage dependent sodium channels.…”

Urodynamic assessment during intravesical infusion of capsaicin for the treatment of refractory detrusor hyperreflexia

“…1,2 Its mechanism of action is based on the interference with Ad thinly myelinated ®bres and sensory unmyelnated C ®bres which mediate the a erent limb of micturation re¯ex in chronic spinal animals. The clinical outcome of intravesical capsaicin, in patients su ering from refractory detrusor hyperre¯exia, has been recently reviewed by a dual-centre study with a long term follow-up.…”