Peripheral antinociceptive effects of a bifunctional μ and 8 opioid receptor ligand in rat model of inflammatory bladder pain

NEUROPHARMACOLOGY

卷:196

Article

Terashvili, Maia¹  Talluri, Bhavana¹  Palangmonthip, Watchareepohn^1,2  Iczkowski, Kenneth A.¹  Sanvanson, Patrick¹  Medda, Bidyut K.¹  Banerjee, Banani¹  Cunningham, Christopher W.³  Sengupta, Jyoti N.¹ 

[1] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[2] Chiang Mai Univ, Fac Med, Dept Pathol, Chiang Mai, Thailand

[3] Concordia Univ, Wisconsin Sch Pharm, Madison, WI USA

关键词: Cystitis;    Opioids;    Analgesic;    Bladder pain;    Bladder afferents;   

DOI  :  10.1016/j.neuropharm.2021.108701

来源: Elsevier

【 摘 要 】

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 mu-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 mu-opioid receptor agonist/8-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 mu, 8, and mu-8 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 mu-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 mu-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.

【 授权许可】

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