Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons.

Nociceptin/Orphanin FQ and Urinary Bladder.

Following identification as the endogenous ligand for the NOP receptor, nociceptin/orphanin FQ (N/OFQ) has been shown to control several biological functions including the micturition reflex. N/OFQ elicits a robust inhibitory effect on rat micturition by reducing the excitability of the afferent fibers. After intravesical administration N/OFQ increases urodynamic bladder capacity and volume threshold in overactive bladder patients but not in normal subjects.

TRPV4 as a target for bladder overactivity.

Several papers published in the last 2-3 years suggest that transient receptor potential vanilloid 4 (TRPV4) channels are candidates as mechanosensors in the urinary bladder (including human) and indicate that modulation (inhibition) of these channels could represent a novel therapy for overactive bladder and storage dysfunction. The effects of only agonists on the bladder have been described up to now, although some compounds endowed with antagonistic activity were reported in the last year. Therefore, it is to be hoped that the effects of these compounds in different models of bladder overactivity will be evaluated.

Effect of selective antagonists of group I metabotropic glutamate receptors on the micturition reflex in rats.

Objective: To investigate the role of Group I metabotropic glutamate (mGlu) receptor subtypes on reflex-induced micturition in anaesthetized and conscious rats using selective mGlu1 (NPS 2407 and R214127) and mGlu5 (MPEP, MTEP, and SIB1893) allosteric antagonists.

Materials And Methods: The affinity of the compounds at mGlu1 and mGlu5 receptor subtypes was evaluated by displacement of tritiated R214127 and MPEP, respectively, from rat brain tissue. Effects of intravenous (i.

Effect of cyclooxygenase inhibitors on the micturition reflex in rats: correlation with inhibition of cyclooxygenase isozymes.

Objective: To investigate the role of cyclooxygenase (COX) isozymes (COX-1 and -2) in the regulation of bladder volume capacity (BVC) in several rat urodynamic models, using a selection of nonsteroidal anti-inflammatory drugs (NSAIDs), some selective for COX-2, correlating the potency of the tested compounds in the urodynamic models and their in vitro potency as inhibitors of COX isozymes, to verify the relative importance of the different isozymes.

Materials And Methods: The effects of an i.v.

Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions.

Background: Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions.

Effect of citalopram, amineptine, imipramine and nortriptyline on stress-induced (footshock) analgesia in rats.

The influence of the oral administration of different doses of citalopram (5, 15 and 45 mg/kg), imipramine (15, 30, 45 and 60 mg/kg), nortriptyline (15, 45 and 60 mg/kg) and amineptine (45 mg/kg) on stress-induced analgesia has been studied in anaesthetized rats. None of the administered antidepressants seem to have appreciable analgesic activity when analgesia is tested by the tail-immersion method. Citalopram, imipramine and nortriptyline, but not amineptine, increase the analgesia induced by inescapable footshock delivered continuously for 2 min to rats.