Transcript Style B 24 by 48 wide - Loyola University Chicago

Efficacy of a novel synthetic topically applied tetrapeptide on eliciting corneal analgesia
subsequent to experimentally induced chemical corneal injury
Bruce I. Gaynes, OD, Pharm D, Michael Russo, David Goldmeier
Loyola University Chicago, Stritch School of Medicine, Department of Ophthalmology, Maywood, IL
Introduction
• Currently, only limited medical
alternatives are available to obtain
adequate corneal analgesia following
various corneal insults, either
iatrogenic, traumatic or disease
related.
• Effective corneal analgesics must
provide adequate pain relief without
compromise of corneal sensitivity.
• Interestingly, viper venom appears to
demonstrate marked analgesic
properties. Chromatographic
fractionation of venoms demonstrated
that low molecular weight fractions
consist of peptides that impart
significant analgesics properties.
• Here we describe the action of the
synthetic analogue of the low
molecular weight venom fraction pGluAsn-Trp-Thr-OH (SIS-ZEP04) for
topical use as a potential corneal
analgesic.
 Study Purpose: To ascertain efficacy
of SIS-ZEP04 in reducing pain in a rat
model of experimentally induced
chemical corneal injury.
Methods
• Five adult Sprague Dawley rats were
utilized for study. All procedures were
approved by the local animal use
committee. The capsaicin eye wipe
test was employed as a mechanism
to ascertain analgesic efficacy.1,2
Summary
Methods
• Administration of 20 µL of 0.01 mg/mL
of tetrapeptide in 0.01% ethanol
vehicle was applied to the right eye for
14 days. A negative control was
employed in the fellow eye.
• Capsaicin testing was performed at
baseline, day 7 and 14.
• The time required for recovery from
capsaicin induced corneal insult,
defined as blepharospasm, eye
wiping, and squinting was recorded as
a surrogate indicator of analgesic
efficacy in relation to the control eye.
Results
• Mean time (seconds) for recovery from
capsaicin induced irritation in both right
and left eyes at baseline was 38.0 +/7.8 and 52.2 +/- 9.8 seconds
respectively.
• Following SIS-ZEP04 treatment (at day
14) mean (SD) time for capsaicin
induced irritation recovery was 12.8 +/5.6 and 24.4 +/- 14.7 seconds for right
and left eyes respectively (Tables 1
and 2).
• A statistically significant reduction in
mean time of capsaicin recovery was
found for both right and left eyes
(paired one way t test, p=0.0250 and
0.0072 respectively, Figure 1+).
• Cochet-Bonnet aesthesiometry
measurements did not deviate from
baseline levels at day 7 or 14 for either
eye.
• Intermediate day 7 capsaicin results
did not differ significantly between
treatment and control groups.
Table 1. Descriptive values, blepharospasm recovery time
(seconds+)
right eye
baseline
Number of values
Minimum
Maximum
Mean
Std. Deviation
4
31.00
49.00
38.00
7.746
right eye
2 weeks
4
6.000
19.00
12.75
5.560
left eye
baseline
5
42.00
62.00
52.20
9.757
left eye
2 weeks
5
13.00
50.00
24.40
14.69
Table 2. Power analysis*
T test
matched pairs
Analysis
Input
Calculated
effect size
Total sample
size
Power (1-β)
Post-hoc
one tailed
2.4598
4
0. 974965
*G*Power
v3.1.7
+GraphPad Prism v5.00
• SIS-ZEP04 appears to demonstrate
efficacy in reducing pain and
modifying pathways of nociception
following chemical irritation in a
capsaicin model of corneal insult.
• As analgesic action was apparent in
both treated and control eyes, it is
unclear what effect, if any, the vehicle
exerted in minimizing ocular pain or
rather if a central action induced by
systemic absorption of the peptide is
in place.
• The analgesic action appears to be a
delayed action and occurs without
reduction in corneal sensitivity.
• Further study is required to clarify the
mechanism by which this novel
peptide appears to exert analgesia in
the mammalian eye as well as
ramifications of potential systemic
absorption.
References
1. Farazifard R. Safarpour F, Sheibani V,
Javan M. Eye-wiping test: a sensitive
animal model for acute trigeminal pain
studies. Brain Research Protocols.
2005;16:44-49
2. Bates, BD, Mitchell K, Keller MM, Chan
CC, Swaim WD, Yaskovich R, Mannes
AJ, Iadarola MJ. Prolonged analgesic
response of cornea to topical
resiniferatoxin., a potent TRPV1 agonist.
Pain. 2010;149:522-528
Acknowledgments: We would like to acknowledge the support of
the Shulov Institute of Science (SIS) Ltd. Rehovot, Israel and the
Richard A. Perritt Charitable Foundation in the conduct of this
work. SIS ZEP04 was kindly provided by Dr. Naftali Primor of
Shulov Institute of Science Ltd.