Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat

R. M. Craft, Samuel Monroe Cohen, F. Porreca

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10-100 nmol) or CAP (10-100 μmol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2-3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 μg/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment). The present study demonstrates that a single, local exposure to RTX produces desensitization of bladder afferents that lasts approximately 2 months, and that intervening exposures to a 10-fold lower dose do not significantly enhance desensitization. RTX is approximately 1000 times more potent than CAP in producing desensitization in this behavioral model, but only 100-300 times more potent in producing tissue inflammation, suggesting that RTX may be superior to CAP as a desensitization therapy.

Original languageEnglish (US)
Pages (from-to)317-323
Number of pages7
JournalPain
Volume61
Issue number2
DOIs
StatePublished - Jan 1 1995

Fingerprint

Capsaicin
Urinary Bladder
resiniferatoxin
Inflammation
Irritants

Keywords

  • Bladder
  • Capsaicin
  • Desensitization
  • Resiniferatoxin

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Neurology
  • Pharmacology
  • Psychiatry and Mental health
  • Neuroscience(all)
  • Clinical Psychology

Cite this

Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat. / Craft, R. M.; Cohen, Samuel Monroe; Porreca, F.

In: Pain, Vol. 61, No. 2, 01.01.1995, p. 317-323.

Research output: Contribution to journalArticle

@article{a4c9dc16e7dd4a86a4bc59648d331884,
title = "Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat",
abstract = "The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10-100 nmol) or CAP (10-100 μmol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2-3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 μg/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment). The present study demonstrates that a single, local exposure to RTX produces desensitization of bladder afferents that lasts approximately 2 months, and that intervening exposures to a 10-fold lower dose do not significantly enhance desensitization. RTX is approximately 1000 times more potent than CAP in producing desensitization in this behavioral model, but only 100-300 times more potent in producing tissue inflammation, suggesting that RTX may be superior to CAP as a desensitization therapy.",
keywords = "Bladder, Capsaicin, Desensitization, Resiniferatoxin",
author = "Craft, {R. M.} and Cohen, {Samuel Monroe} and F. Porreca",
year = "1995",
month = "1",
day = "1",
doi = "10.1016/0304-3959(94)00193-I",
language = "English (US)",
volume = "61",
pages = "317--323",
journal = "Pain",
issn = "0304-3959",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat

AU - Craft, R. M.

AU - Cohen, Samuel Monroe

AU - Porreca, F.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10-100 nmol) or CAP (10-100 μmol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2-3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 μg/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment). The present study demonstrates that a single, local exposure to RTX produces desensitization of bladder afferents that lasts approximately 2 months, and that intervening exposures to a 10-fold lower dose do not significantly enhance desensitization. RTX is approximately 1000 times more potent than CAP in producing desensitization in this behavioral model, but only 100-300 times more potent in producing tissue inflammation, suggesting that RTX may be superior to CAP as a desensitization therapy.

AB - The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10-100 nmol) or CAP (10-100 μmol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2-3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 μg/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment). The present study demonstrates that a single, local exposure to RTX produces desensitization of bladder afferents that lasts approximately 2 months, and that intervening exposures to a 10-fold lower dose do not significantly enhance desensitization. RTX is approximately 1000 times more potent than CAP in producing desensitization in this behavioral model, but only 100-300 times more potent in producing tissue inflammation, suggesting that RTX may be superior to CAP as a desensitization therapy.

KW - Bladder

KW - Capsaicin

KW - Desensitization

KW - Resiniferatoxin

UR - http://www.scopus.com/inward/record.url?scp=0029075577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029075577&partnerID=8YFLogxK

U2 - 10.1016/0304-3959(94)00193-I

DO - 10.1016/0304-3959(94)00193-I

M3 - Article

VL - 61

SP - 317

EP - 323

JO - Pain

JF - Pain

SN - 0304-3959

IS - 2

ER -