Targeting sickle pain with novel therapies and developing methods to quantify pain

• Kalpna Gupta

• Vascular Biology Centre• Division of Hematology, Oncology and

Transplantation• Department of Medicine

• University of Minnesota Medical School• Minneapolis, MN

• Email: gupta014@umn.edu

Pain(Nociception)

Spinal Activation

Phospho-P38/MAPK ERKTLR4↑ IL6↑ COX-2

Leg ulcer

Hypoxia, ischemia, reperfusion injury

Vascular/neural aberrations

Free heme Inflammation

Pain in Sickle Cell Disease: A complex synergism between peripheral and central mechanisms

• How do we quantify pain?

• How do we convey the “pain” as soon as it starts to the healthcare providers?

• Can diet and alternative therapies help reduce pain?

• What are the potential novel therapies to treat pain without an inadvertent effect?

Recognizing the problem and finding solutions to treat sickle pain

Action Units Normal (~22˚C) Cold (4˚C)

Eyes are more circular and open

Eyes are tightly squeezed, and oval shape

Ears erect & perpendicular to the neck line

Ears are parallel to the neck line

Nose is smooth without skin tightening

Tightening of nose with an extension of skin visible

Cheek is smooth

Convex, similar to “puffing” of cheeks

Orbital Tightening

Ear Position

Cheek Bulge

Nose Bulge

Cold leads to changes in facial expressions

Facial expression readout to quantify pain from remote access?

Goal: To develop pain quantification on images transmitted through a cell phone from the patient’s home to the healthcare provider at a distant location.Lucey et al. Int Conf Affect Comput Intell Interact Workshops. 2009:1-8

Thakur AS, et al. Hematological Parameters and RBC TBARS Level of CoQ10 Supplemented Tribal Sickle Cell Patients: A Hospital Based Study. Indian J Clin Biochem. 2013 Apr;28(2):185-8

Dose Coenzyme Q10: 15 mg/Kg/dayCurcumin: 45 mg/Kg/day

Curcumin and CoQ10 reduce pain in sickle mice

†, vs HbSS RD/M-*, vs BL

High calorie diet and mating attenuate pain in sickle mice.

Incr

ease

of m

echa

nica

l hyp

eral

gesi

aMechanical

BL 1 2 30

2

4

6

8

10

PW

F (

1.0

g f

ibe

r)

HbSS RD/M-

HbAA RD/M-

HbSS SD/M+

HbAA SD/M+

HbSS SD/M-HbSS RD/M+

†††† †††

****

**** ****††

††††

†

*

*

*

Treatment (weeks)

††

Sickle

Control

vehicle

treatments

Potential strategies to improve pain treatment

Cannabinoids?

AT-200 a nociceptin receptor agonist provides analgesia in chronic and hypoxia/reoxygenation induced pain in sickle mice.

Mast cell inhibition with imatinib may reduce pain and improve the sensitivity to opioid-analgesia.

Salubrinal reduces pain and increases HbF expression in human erythroid cells.

NHLBI, UO1HL117664; RO1: HL68802; HL103733; HL68802-06S1; HL68802-7S1

Institute for Engineering in MedicineUniversity of Minnesota Foundation

Dean’s and Department of Medicine Funds

CollaboratorsSaad Bedros, EngineeringBin He, EngineeringWei Chen, Engineering

Univ of MN ResourcesUniversity Imaging CentreResearch Animal ResourcesCharacterization Facility (EM)Cancer CenterCTSIMSI

Carol Taubert (Illustrations)

Lab MembersYing Wang, MD, PhDHuy TranJianxun Lei, PhDJinny A Paul, PhDLucile Vincent, PhDYessenia Guevara, PhDYann Lamarre, PhDMaureen Reidl, PhDJoe Cataldo, PhDMegan Uhelski, PhD

Lab MembersJulia NguyenBarbara BensonRitu JhaKathryn LukSusan ThompsonLindsey SkubitzThu DuongJonathan Luk PaulAditya M MittalDeniz Arcan-Fang

ACKNOWLEDGEMENTS