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Noor et al. Neuroimmunol Neuroinflammation 2019;6:10 Neuroimmunology
DOI: 10.20517/2347-8659.2019.18 and Neuroinflammation

Original Article Open Access

LFA-1 antagonist (BIRT377) similarly reverses
peripheral neuropathic pain in male and female mice

with underlying sex divergent peripheral immune
proinflammatory phenotypes

Shahani Noor , Melody S. Sun , Arden G. Vanderwall , Mara A. Havard , Jacob E. Sanchez , Nathan
2
1
1,2
1#
1#
W. Harris , Monique V. Nysus , Jeffrey P. Norenberg , Harrison T. West , Carsten R. Wagner , Lauren L.
5
1
4
5
4
Jantzie , Nikolaos Mellios , Erin D. Milligan 1
1
3
1 Department of Neurosciences, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
2 Department of Anesthesiology and Critical Care, University of New Mexico, Albuquerque, NM 87131, USA.
3 Department of Pediatrics and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
4 Department of Radiopharmaceutical Sciences, College of Pharmacy, New Mexico Center for Isotopes in Medicine, University
of New Mexico, Albuquerque, NM 87131, USA.
5 Department of Medicinal Chemistry, University of Minnesota, College of Pharmacy, Minneapolis, MN 55455, USA.
# Author contributed equally to this work.
Correspondence to: Dr. Shahani Noor, Department of Neurosciences, School of Medicine, University of New Mexico,
Albuquerque, NM 87131,USA. E-mail: snoor@salud.unm.edu; Prof. Erin D. Milligan, Department of Neurosciences, School of
Medicine, University of New Mexico, Albuquerque, NM 87131, USA. E-mail: EMlilligan@salud.unm.edu
How to cite this article: Noor S, Sun MS, Vanderwall AG, Havard MA, Sanchez JE, Harris NW, Nysus MV, Norenberg JP, West
HT, Wagner CR, Jantzie LL, Mellios N, Milligan ED. LFA-1 antagonist (BIRT377) similarly reverses peripheral neuropathic pain
in male and female mice with underlying sex divergent peripheral immune proinflammatory phenotypes. Neuroimmunol
Neuroinflammation 2019;6:10. http://dx.doi.org/10.20517/2347-8659.2019.18
Received: 29 May 2019 First Decision: 18 Jul 2019 Revised: 6 Jul 2019 Accepted: 8 Jul 2019 Published: 22 Jul 2019
Science Editor: Athanassios P. Kyritsis Copy Editor: Jia-Jia Meng Production Editor: Jing Yu

Abstract
Aim: The majority of preclinical studies investigating aberrant glial-neuroimmune actions underlying neuropathic
pain have focused on male rodent models. Recently, studies have shown peripheral immune cells play a more
prominent role than glial cells in mediating pathological pain in females. Here, we compared the onset and duration
of allodynia in males and females, and the anti-allodynic action of a potentially novel therapeutic drug (BIRT377)
that not only antagonizes the action of lymphocyte function-associated antigen-1 (LFA-1) to reduce cell migration in
the periphery, but may also directly alter the cellular inflammatory bias.

Methods: Male and female mice were subjected to peripheral nerve injury chronic constriction injury (CCI) applying
two methods, using either 4-0 or 5-0 chromic gut suture material, to examine potential sex differences in the

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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