PMID- 36549668
OWN - NLM
STAT- MEDLINE
DCOM- 20230505
LR  - 20230505
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 180
IP  - 11
DP  - 2023 Jun
TI  - TRPV1 and TRPM8 antagonists reduce cystitis-induced bladder hypersensitivity via 
      inhibition of different sensitised classes of bladder afferents in guinea pigs.
PG  - 1482-1499
LID - 10.1111/bph.16017 [doi]
AB  - BACKGROUND AND PURPOSE: Interstitial cystitis (=painful bladder syndrome) is a 
      chronic bladder syndrome characterised by pelvic and bladder pain, urinary 
      frequency and urgency, and nocturia. Transient receptor potential (TRP) channels 
      are an attractive target in reducing the pain associated with interstitial 
      cystitis. The current study aims to determine the efficacy of combination of TRP 
      vanilloid 1 (TRPV1) and TRP melastatin 8 (TRPM8) channel inhibition in reducing 
      the pain associated with experimental cystitis in guinea pigs. EXPERIMENTAL 
      APPROACH: A novel animal model of non-ulcerative interstitial cystitis has been 
      developed using protamine sulfate/zymosan in female guinea pigs. Continuous 
      voiding cystometry was performed in conscious guinea pigs. Ex vivo 
      "close-to-target" single unit extracellular recordings were made from fine 
      branches of pelvic nerves entering the guinea pig bladder. Visceromotor responses 
      in vivo were used to determine the effects of TRP channel antagonists on 
      cystitis-induced bladder hypersensitivity. KEY RESULTS: Protamine sulfate/zymosan 
      treatment evoked mild inflammation in the bladder and increased micturition 
      frequency in conscious animals. In cystitis, high threshold muscular afferents 
      were sensitised via up-regulation of TRPV1 channels, high threshold 
      muscular-mucosal afferents were sensitised via TRPM8 channels, and mucosal 
      afferents by both. Visceromotor responses evoked by noxious bladder distension 
      were significantly enhanced in cystitis and were returned to control levels upon 
      administration of combination of low doses of TRPV1 and TRPM8 antagonists. 
      CONCLUSIONS AND IMPLICATIONS: The data demonstrate the therapeutic promises of 
      combination of TRPV1 and TRPM8 antagonists for the treatment of bladder 
      hypersensitivity in cystitis.
CI  - (c) 2022 British Pharmacological Society.
FAU - Ramsay, Stewart
AU  - Ramsay S
AUID- ORCID: 0000-0003-2068-3868
AD  - Discipline of Human Physiology, Flinders Health and Medical Research Institute, 
      College of Medicine and Public Health, Flinders University, Adelaide, South 
      Australia, Australia.
FAU - Keightley, Lauren
AU  - Keightley L
AD  - Discipline of Human Physiology, Flinders Health and Medical Research Institute, 
      College of Medicine and Public Health, Flinders University, Adelaide, South 
      Australia, Australia.
FAU - Brookes, Simon
AU  - Brookes S
AD  - Discipline of Human Physiology, Flinders Health and Medical Research Institute, 
      College of Medicine and Public Health, Flinders University, Adelaide, South 
      Australia, Australia.
FAU - Zagorodnyuk, Vladimir
AU  - Zagorodnyuk V
AUID- ORCID: 0000-0001-6418-7482
AD  - Discipline of Human Physiology, Flinders Health and Medical Research Institute, 
      College of Medicine and Public Health, Flinders University, Adelaide, South 
      Australia, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230113
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Transient Receptor Potential Channels)
RN  - 0 (TRPV Cation Channels)
RN  - 9010-72-4 (Zymosan)
RN  - 0 (TRPM Cation Channels)
SB  - IM
MH  - Animals
MH  - Female
MH  - Guinea Pigs
MH  - *Cystitis/drug therapy
MH  - *Cystitis, Interstitial
MH  - *Hypersensitivity
MH  - Pain
MH  - *Transient Receptor Potential Channels
MH  - TRPV Cation Channels
MH  - Urinary Bladder
MH  - Zymosan/pharmacology
MH  - TRPM Cation Channels/antagonists & inhibitors
OTO - NOTNLM
OT  - TRPM8 channels
OT  - TRPV1 channels
OT  - bladder afferents
OT  - bladder hypersensitivity
OT  - cystitis
OT  - visceromotor responses
EDAT- 2022/12/23 06:00
MHDA- 2023/05/03 06:42
CRDT- 2022/12/22 19:42
PHST- 2022/11/25 00:00 [revised]
PHST- 2022/06/13 00:00 [received]
PHST- 2022/12/19 00:00 [accepted]
PHST- 2023/05/03 06:42 [medline]
PHST- 2022/12/23 06:00 [pubmed]
PHST- 2022/12/22 19:42 [entrez]
AID - 10.1111/bph.16017 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2023 Jun;180(11):1482-1499. doi: 10.1111/bph.16017. Epub 2023 Jan 
      13.