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364 A

IMAGING AND NON-INVASIVE MEASUREMENT OF


CAPSAICIN INDUCED DERMAL BLOOD FLOW.

Rao V. L. Papineni*, Sunil Reddy#, Sean Orton,


William McLaughlin, Douglas Vizard, John
Pizzonia, and M.U.R. Naidu#.
Carestream Molecular Imaging, 4 Research Dr., Woodbridge,
CT, 06525, USA and # NIMS, Hyderabad, India.
* rao.papineni1@carestreamhealth.com

Abstract Capsaicin Action in Dermal Vasodilation


Capsaicin effects neurogenic inflammation and a
localized vasodilation by activating transient receptor
potential vanilloid type 1 receptor (TRPV1). Topical
application of capsaicin on the human forearm results in
Dermal Vasodilation
increased dermal blood flow (DBF). Capsaicin induced Dr. Papineni
changes in the microvascular dynamics at the dermis, is
mainly driven through the calcitonin gene-related
peptide (CGRP) receptor activation. There is growing
evidence suggesting that endothelial dysfunction is an
important and an early event in the pathogenesis of
major cardiovascular diseases. Novel sensitive and
robust methodologies are becoming essential in clinics CGRP
Capsaicin
to determine endothelial function in dermal circulation
Substance P
non-invasively. Here, we have utilized two approaches Prostaglandins
to both compare and validate the methodologies in Nitric Oxide
determination of the DBF. In the method-1, RBC Neurokinin A
perfusion was carried out in healthy human subjects Histamine TRPV1
using Laser Doppler Flowmetry. Measurements were
made after 30 min of topical application of capsaicin
(0.075%) on one arm and saline on the other arm
(control). Significant change in the DBF was observed Vasodilation Neurogenic Inflammation Activation
in the arm applied with capsaicin- the mean blood flow
increased from 25.7 bpu to 83.5 bpu. The mean blood
flow change in the control arm however showed Capsaicin Induced Dermal Blood Flow. The cartoon shows the activation of transient
negligible changes (26.1 bpu to 26.6 bpu). In the receptor potential vanilloid type I receptor (TRPV1) by capsaicin. The resultant neurogenic
second method, we determined the dermal blood flow in inflammation and vasodilation are evoked by the release of calcitonin gene-related peptide
response to the topical application of capsaicin using a (CGRP), NO, Substance P and prostaglandins. The neuropeptide CGRP is the major
planar optical imaging setup. Fluorescence images player in the capsaicin induced dermal blood flow.
were captured to determine the capsaicin-induced
dermal blood flow. The results indicate the possibility of
utilizing inexpensive optical imaging in the clinical and
pharmaceutical fields in microvascular dynamic analysis
and testing endothelial function in clinical studies. Also,
provides opportunity for rapid screening of novel
compound antagonists of CGRP receptor that block the
Changes in Dermal Microvascular Dynamics
capsaicin-induced DBF. 35
500

30
300

25
BPU (a.u)

BPU (a.u)

20
200

15

Materials and Methods 10


100

Laser Doppler Flowmetry (LDF) from BIOPAC was used to 5

measure dermal blood flow. The Llaser Doppler microvascular 0


perfusion module monitors the red blood cell perfusion in the 0 2 4 6 8 10 12 14 16 18 20 22 24 0
1 2 3 4 5 6 7 8 9 10

microcirculation. Laser Doppler signals are recorded as Dominant Arm

BPU (Blood Perfusion units). Healthy Subjects (#) Non-dominant Arm Healthy Subjects (#)
The data from 24 healthy human subjects (Upper Left Panel) were obtained using LDF to validate the blood
Pea size capsaicin was applied to the skin to evoke the perfusion Unit (BPU) measurement technique. The data from left arm (dark red Bar) and the Right arm (orange
pharmacological response in healthy individuals. The time of Bar) show negligible changes in BPU. In response to the capsaicin (0.075%) treatment (Upper Right Panel), the
incubation was for 30 min before measurement. In the case of ten individuals show significant changes in the dermal blood flow (BPU). Capsaicin was applied to non-dominant
optical imaging, 15 min incubation protocol was observed. arm while cold cream was applied to dominant arm. The changes also seem to be related to the time (AM or PM)
Baseline measurements were performed prior to capsaicin of capsaicin application. The violet sections of the stacked bars represent the baseline, and the blue regions
application. represent post pharmacological treatment.
Optical Imaging: The microcirculation was
Caucasians, Asian Chinese, South Asian, adult volunteers were determined using Carestream Developmental
enrolled after full explanation of the studies. All individuals completed Phase-Planar Optical Imaging Set-up (Left Two
the study per protocol. Panels).
Non-invasive imaging of healthy subject’s hand: pre
(left-upper panel) and post-capsaicin treatment (left-
lower panel) were performed. The surface plots of
Dermal Imaging – Optical Imager the natural fluorescence with the raw images (inset)
are shown here. Ex 620 EM 700; F-Stop: 2.8, no
binning.

Conclusions
Hand

Dermal blood flow in response to capsaicin treatment


is determined by planar optical imaging utilizing
CCD natural fluorescence.
400 watt
EX 620 Data indicates a circadian rhythmic nature in dermal
microvascular dynamics when responding to
capsaicin treatment- a direction we are currently

The above schematic describes the Carestream Developmental pursing.


phase “Planar Optical Imaging set-up” designed to image human The feasibility of utilizing the imaging approach in
hand. A 400-Watt Xenon illuminator has been applied to image the measuring dermal blood flow provides promise and
natural fluorescence at the interphalangeal joints and the whole Arm.
opportunity to adapt the methodology in detection of
endothelial dysfunction.
Carestream is a trademark of Carestream Health, Inc. The Kodak trademark is used under license from Kodak. Carestream
Molecular Imaging is a division of Carestream Health, Inc. LDF100C is the trademark of BIOPAC Systems Inc. Capzasin-HP is the
trademark of CHATTEM.

© Carestream Health, Inc.


"Molecular Imaging - Wisdom To See For Maladies To Flee"
Dr. Rao V. L. Papineni

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