Intrathecal delivery of resiniferatoxin (RTX) reduces detrusor overactivity and spinal expression of TRPV1 in spinal cord injured animals.
Recently, it has been demonstrated that intrathecal delivery of resiniferatoxin (RTX) produces strong analgesia, even in models of bone cancer pain. RTX has been investigated to treat bladder dysfunction of spinal origin, applied by intravesical instillation. However, RTX delivered by this route was not completely satisfactory in controlling urinary incontinence and high intravesical pressure. Thus, the present study assessed the effects of intrathecal injections of RTX in bladder dysfunction in rats with spinal cord transection (SCT). Bladder function was evaluated in SCT rats 24 h following intrathecal administration of RTX. Detrusor overactivity and intravesical pressure were reduced in a dose-dependent manner. This was accompanied by a decrease in spinal cord TRPV1 and CGRP, but not in IB4 binding sensory fibres. Also, intrathecal RTX induced a dose-dependent reduction in spinal cord activation of the ERK pathway. Overall, our results show that intrathecal administration of RTX effectively reduces detrusor overactivity and reduces intravesical pressure in models of complete chronic spinal cord transection by suppressing the activity of TRPV1 expressing afferent fibres. Also, intrathecal RTX decreases sensory input, as shown by reduced spinal ERK activation. These findings might be relevant for the management of patients with spinal cord injuries.
Cruz
Célia D
CD
Institute of Histology and Embryology, Faculty of Medicine and IBMC-Instituto de Biologia Molecular e Celular, University of Porto, Portugal. ccruz@med.up.pt
Charrua
Ana
A
Vieira
Eva
E
Valente
João
J
Avelino
António
A
Cruz
Francisco
F
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D007278:Injections, Spinal; D037102:Lectins; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications*; D050916:TRPV Cation Channels / Q000378:metabolism*; D001743:Urinary Bladder / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000209:etiology; D014554:Urination / Q000187:drug effects
D004224:Diterpenes; C496198:IB4-saporin conjugate; D037102:Lectins; D009498:Neurotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C024353:resiniferatoxin; D048049:Extracellular Signal-Regulated MAP Kinases; D000076985:Saporins; D015740:Calcitonin Gene-Related Peptide