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Peripheral antinociceptive effects of a bifunctional µ and δ opioid receptor ligand in rat model of inflammatory bladder pain.
Terashvili, Maia; Talluri, Bhavana; Palangmonthip, Watchareepohn; Iczkowski, Kenneth A; Sanvanson, Patrick; Medda, Bidyut K; Banerjee, Banani; Cunningham, Christopher W; Sengupta, Jyoti N.
Afiliação
  • Terashvili M; Medical College of Wisconsin, USA.
  • Talluri B; Medical College of Wisconsin, USA.
  • Palangmonthip W; Medical College of Wisconsin, USA; Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
  • Iczkowski KA; Medical College of Wisconsin, USA.
  • Sanvanson P; Medical College of Wisconsin, USA.
  • Medda BK; Medical College of Wisconsin, USA.
  • Banerjee B; Medical College of Wisconsin, USA.
  • Cunningham CW; Concordia University Wisconsin School of Pharmacy, Wisconsin, USA.
  • Sengupta JN; Medical College of Wisconsin, USA. Electronic address: sengupta@mcw.edu.
Neuropharmacology ; 196: 108701, 2021 09 15.
Article em En | MEDLINE | ID: mdl-34256047
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oximorfona / Raízes Nervosas Espinhais / Compostos de Benzilideno / Receptores Opioides delta / Receptores Opioides mu / Cistite Intersticial / Mecanotransdução Celular / Analgésicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oximorfona / Raízes Nervosas Espinhais / Compostos de Benzilideno / Receptores Opioides delta / Receptores Opioides mu / Cistite Intersticial / Mecanotransdução Celular / Analgésicos Idioma: En Ano de publicação: 2021 Tipo de documento: Article