Faculty Collaboration Database

Peripheral antinociceptive effects of a bifunctional μ and δ opioid receptor ligand in rat model of inflammatory bladder pain. Neuropharmacology 2021 Sep 15;196:108701

Date

07/14/2021

Pubmed ID

34256047

Pubmed Central ID

PMC8435000

DOI

10.1016/j.neuropharm.2021.108701

Scopus ID

2-s2.0-85110016880 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

There is a need to develop a novel analgesic for pain associated with interstitial cystitis/painful bladder syndrome (IC/PBS). The use of the conventional μ-opioid receptor agonists to manage IC/PBS pain is controversial due to adverse CNS effects. These effects are attenuated in benzylideneoxymorphone (BOM), a low-efficacy μ-opioid receptor agonist/δ-opioid receptor antagonist that attenuates thermal pain and is devoid of reinforcing effects. We hypothesize that BOM will inhibit bladder pain by attenuating responses of urinary bladder distension (UBD)-sensitive afferent fibers. Therefore, the effect of BOM was tested on responses of UBD-sensitive afferent fibers in L6 dorsal root from inflamed and non-inflamed bladder of rats. Immunohistochemical (IHC) examination reveals that following the induction of inflammation there were significant high expressions of μ, δ, and μ-δ heteromer receptors in DRG. BOM dose-dependently (1-10 mg/kg, i.v) attenuated mechanotransduction properties of these afferent fibers from inflamed but not from non-inflamed rats. In behavioral model of bladder pain, BOM significantly attenuated visceromotor responses (VMRs) to UBD only in inflamed group of rats when injected either systemically (10 mg/kg, i.v.) or locally into the bladder (0.1 ml of 10 mg/ml). Furthermore, oxymorphone (OXM), a high-efficacy μ-opioid receptor agonist, attenuated responses of mechanosensitive bladder afferent fibers and VMRs to UBD. Naloxone (10 mg/kg, i.v.) significantly reversed the inhibitory effects of BOM and OXM on responses of bladder afferent fibers and VMRs suggesting μ-opioid receptor-related analgesic effects of these compounds. The results reveal that a low-efficacy, bifunctional opioid-based compound can produce analgesia by attenuating mechanotransduction functions of afferent fibers innervating the urinary bladder.

Author List

Terashvili M, Talluri B, Palangmonthip W, Iczkowski KA, Sanvanson P, Medda BK, Banerjee B, Cunningham CW, Sengupta JN

Authors

Bidyut K. Medda PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Patrick P. Sanvanson MD Associate Professor in the Medicine department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Afferent Pathways
Analgesics
Animals
Benzylidene Compounds
Cystitis, Interstitial
Disease Models, Animal
Lumbar Vertebrae
Mechanotransduction, Cellular
Naloxone
Narcotic Antagonists
Oxymorphone
Rats
Receptors, Opioid, delta
Receptors, Opioid, mu
Spinal Nerve Roots