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Nociceptin/orphanin phenylalanine glutamine (N/OFG) is a heptadecapeptide (Meunier et al. 1995; Reinscheid et al. 1995) that affects the sensory innvervation of the lower urinary tract in a similar fashion to CAP and RTX. It activates the G protein coupled receptor nociceptin orphan peptide and thus has an inhibitory effect on the micturition reflex in the rat (Lecci et al. 2000).

Table 4 Nociception/Orphanin Phenylalanine Glutamine

Author Year

Country
Research Design
Score
Total Sample Size

MethodsOutcome
Lazzeri et al. 2003

Italy
RCT

PEDro=10

N=14

Population: SCI subjects with neurogenic detrusor overactivity: Mean Age (treatment): 43.7 yr; Mean age (placebo): 41.4 yr; Gender: males=6, females=8; Level of Injury: T4-L2; Cause of injury: trauma=10, non-trauma=4 (ratio 5:2 per group); Time post-injury (treatment): 8.7 yr; Time post-injury (control): 7.0 yr.

Intervention: A randomized placebo double blind study evaluating the neuropeptide nociceptin/orphanin (N/OFG) versus placebo.

Outcome Measures: Bladder capacity, volume threshold for the appearance of detrusor overactivity (DO), and maximal bladder pressure during involuntary bladder contractions.

1.     N/OFQ resulted in significant increase in:

·     Capacity (p<0.001)

·     DO volume threshold (p<0.01).

2.     N/OFQ resulted in a non-significant decrease in:

·     Max bladder pressure

3.     No difference between N/OFG and Placebo in:

·     No phasic contractions or autonomic dysreflexia

·     Incomplete individuals – no suprapubic or urethral sensation

·     Vital signs unchanged.

4.     N/OFQ (but not placebo) elicits robust acute inhibitory effect on micturition reflex in individuals with neurogenic bladder.

Lazzeri et al. 2006

Italy

RCT

PEDro=8

N=18

Population: Neurogenic detrusor overactivity. Treatment: Mean age: 37.1 yr; Gender: males=4, females=5; Placebo: Mean age: 44.9 yr; Gender: males=4, females=5

Intervention: SCI individuals were randomly placed into the treatment group receiving 1 mg of nociceptin/orphanin FQ/d for 10 days or placebo.

Outcome Measures: Bladder pressure, Incontinence Episode Frequency (IEF), Voiding Diary-Bladder Capacity (VD-BC).

1.     Post-treatment, mean bladder pressure and IEF decreased significantly (p<0.05) in the treatment group; however, no such change was seen in the placebo group.

2.     No significant difference was seen in the bladder capacity and VD-BC post treatment.

Discussion

Following a successful preliminary human study, Lazzeri et al. (2003) confirmed that N/OFG versus placebo is responsible for a significant increase in bladder capacity (p<0.001) and threshold volume of detrusor overactivity (p<0.001), and a non-significant decrease of maximum bladder pressure of the dysfunctional neurogenic bladder. These results were verified in an additional small-scale RCT (n=18) of a 10 day course of N/OFG treatment versus placebo (saline). Statistically significant improvements to bladder capacity (assessed by daily voiding diary) and urine leakage episodes were seen in the treated group but not with placebo (Lazzeri et al. 2006). The authors conclude that this inhibition of the micturition reflex supports nociceptin orphan peptide receptor agonists as a possible new treatment for neurogenic bladders of SCI individuals.

Conclusion

There is level 1a evidence (from two RCTs; Lazzeri et al. 2003; Lazzeri et al. 2006) that supports the use of nociceptin/orphanin phenylalanine glutamine, a nociceptin orphan peptide receptor agonist for the treatment of neurogenic bladder in SCI.

Nociceptin/orphanin phenylalanine glutamine, a nociceptin orphan peptide receptor agonist, may be considered for the treatment of neurogenic bladder in SCI.