laura.s.stone [at] mcgill.ca (Email)
Tel:(514) 398-7203 ext. 00039
The overall objective of Dr. Stone’s research program is to improve diagnosis and treatment of chronic pain by expanding our understanding of its neurochemistry and neuropathology.
Dr. Stone received her PhD at the University of Minnesota in 1999. As a post-doctoral trainee at the Oregon Health and Sciences University (OHSU), she was the first recipient of the John J. Bonica Post-Doctoral Training Fellowship from the International Association for the Study of Pain (IASP). Following a brief interlude in biotechnology, she returned to academia in 2002. Since that time she has received two NIH R21 grants and a CIHR operating grant as Principal Investigator. Dr. Stone is an inventor on 7 patents, has co-authored over 20 manuscripts and has been recognized for Early Career Scholarship by the American Pain Society (John C. Liebeskind Early Career Scholar Award 2006). Dr. Stone joined the Faculty of Dentistry at McGill University in Jan 2007.
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Many analgesic drugs such as those acting at opioid- or alpha-2-adrenergic receptors interact in a synergistic manner when co-administered in humans or in animal models. This is a important clinically as co-administration of synergistically interacting agents can help maximize analgesia while minimizing adverse side effects. A major goal of my research is to elucidate the underlying mechanism(s) analgesic drug interactions using a multidisciplinary approach that includes behavioral, biochemical, anatomical. electrophysiological and genetic methods. We are currently investigating the hypothesis that the formation of hetero-oligomeric receptor complexes represents a molecular mechanism underlying synergy.
Chronic Back Pain
Persistent back pain is the most common chronic pain condition in Canadians age 65 and under. Unfortunately, the vast majority of individuals suffer for years with little relief. This is due, in part, to a lack of understanding of the underlying causes of back pain. In order to enhance our understanding, we have developed and are currently validating a rodent model of back pain due to degeneration of the spine. Such a model will allow for the identification and testing of novel therapeutic interventions for the alleviation of chronic back pain.
Chronic pain is associated with reduced grey matter and altered activation patterns in certain regions of the brain. The full consequences of these changes are not clear, nor is not known if they can be reversed or attenuated by successful pain management. In collaboration with Post-Doctoral Fellow Dr. David Seminowicz, Orthopedic Surgeon Dr. Jean Ouellet and Pain Management Specialist Dr. Yoram Shir, we are performing a longitudinal study using functional and anatomical magnetic resonance imaging in chronic low back pain patients to determine if successful management by either surgical intervention or spinal injection(s) can reverse or attenuate these changes. We will also determine if the degree of cortical degeneration is linked to a decreased probability that a patient will benefit from treatment. If that is the case, then it will become critical to treat chronic pain early and aggressively in order to prevent grey matter loss.
In collaboration with colleagues from the University of Minnesota, we have developed a research program to characterize the biochemical and anatomical changes that accompany chronic low back pain. We are currently focused on low back pain patients who are scheduled for spinal surgery to remove degenerated lumbar discs for therapeutic reasons. Following documentation pain severity and physical impairment, samples of cerebral spinal fluid obtained from these patients are compared with normal controls for pain-related biomarkers using cutting edge proteomics methods (i.e. LC-MS/MS). In addition, anatomical studies are being performed on lumbar discs (removed as part of surgical treatment) to determine if altered disc biochemistry or innervation patterns contribute to chronic low back pain.
Please Dr. Stone's Google Scholar profile for a complete list of publications
S. Alvarado, M. Tajerian, M Millecamps, M. Suderman, L.S. Stone, M. Szyf; Peripheral Nerve Injury Is accompanied by chronic transciptome-wide changes in the mouse prefrontal cortex. Molecular Pain, in press
M. Tajerian, S. Alvarado, M Millecamps, P Vachon, C. Crosby, M.C. Bushnell, M. Szyf, L.S. Stone; Peripheral Nerve Injury Is Associated with Chronic, Reversible Changes in Global DNA Methylation in the Mouse Prefrontal Cortex. PLOS One, 2013; 8(1), e55259.
L. Low, M. Millecamps, D.A. Seminowicz, L. Naso, S.J. Thompson , L.S. Stone, M.C. Bushnell; Nerve injury causes long-term cognitive deficits in rats; Neuroscience Letters, 2012; 529:103-107.
M. Millecamps, M. Tajerian, L. Naso, L.S Stone; Lumbar Intervertebral Disc Degeneration Associated with Axial and Radicular Low Back Pain in Aging SPARC-null Mice; Pain, 2012; 153(6):1167-79.
M. Tajerian, M. Millecamps, L.S Stone; Morphine and Clonidine Synergize to Ameliorate Low Back Pain in Mice; Pain Research and Treatment, Volume 2012, Article ID150842.
N. Audet, O. Mnie-Filali, M. Amraei, A-J. Chabot-Doré, M. Millecamps, L.S. Stone and G. Pineyro; Differential Association of Receptor-G?? Complexes with ?-arrestin2 Determines Recycling Bias and Potential for Tolerance of Delta Opioid Receptor (DOR) Agonists; J Neuroscience, 32(14):4827– 4840, 2012.
M. Tajerian, S. Alvarado, M. Millecamps, T. Dashwood, K.M. Anderson, L. Haglund, J.A. Ouellet, M. Szyf, L.S Stone; DNA Methylation of SPARC is Associated with Low Back Pain; Molecular Pain, 7(1):65, 2011.
D.A. Seminowicz, T.H. Wideman, L. Naso, Z. Hatami-Khoroushahi, S. Fallatah, M. Ware, P. Jarzem, M.C. Bushnell, Y Shir, J.A. Ouellet, and L.S. Stone; Effective Treatment of Chronic Low Back Pain Reverses Structural and Functional Brain Changes; Journal of Neuroscience, 31(20):7540-7550, 2011.
F.J. Symons, J.J. Wolff, L.S. Stone, T. Lim and J.W. Bodfish; Salivary Biomarkers of HPA Axis and Autonomic Activity in Adults with Intellectual Disability With and Without Stereotyped and Self-Injurious Behavior Disorders; Journal of Neurodevelopmental Disorders: 3(2):144-151, 2011.
M. Millecamps, M. Tajarian, E.H. Sage, and L.S. Stone; Behavioral Signs of Chronic Back Pain in the SPARC-null mouse; Spine, 36(2):95-102, 2011 (NIHMS221485, CAPMC1525).
M. Millecamps, A. Laferrière, J.V. Ragavendran, L.S. Stone and T.J. Coderre; Role of Peripheral Endothelin Receptors in an Animal Model of Complex Regional Pain Syndrome type 1; Pain, 151:174-183, 2010.
M.S. Riedl, S. Schnell, A.C. Overland, A-J. Chabot-Dore, A.M. Taylor, A. Ribeiro-Da-Silva, R. Elde, G.L. Wilcox and L.S. Stone. Co-expression of Alpha-2a-adrenergic and delta-opioid receptors in Substance P terminals in rat dorsal horn. Journal of Comparative Neurology 513(4):385-398; 2009 (NIHMS89435).
C.A. Fairbanks, K.F. Kitto, H.O. Nguyen, L.S. Stone., and G.L. Wilcox. Clonidine and Dexmedetomidine Produce Antinociceptive Synergy in Mouse Spinal Cord. Anesthesiology 110(3):638-47; 2009.
L.S. Stone., K.F. Kitto, J.C. Eisenach, C.A. Fairbanks and G.L. Wilcox. ST91 [2-(2,6-Diethylphenylamino)-2-imidazoline Hydrochloride] - Mediated Spinal Antinociception and Synergy with Opioids Persists in the Absence of Functional Alpha-2A- or Alpha-2C- Adrenergic Receptors. Journal of Pharmacology and Experimental Therapeutics 323(3):899-906 2007.
C.J. Goracke-Postle, A.C. Overland, M.A. Riedl, L.S. Stone.and C.A. Fairbanks. Potassium- and capsaicin-induced release of agmatine from spinal nerve terminals. Journal of Neurochemistry 102:1738-1748; 2007.
L.S. Stone and G.L. Wilcox. Alpha-2-Adrenergic and Opioid Receptor Additivity in Rat Locus Coeruleus Neurons. Neuroscience Letters 361(1-3):265-268; 2004.
L.S. Stone., L. Vulchanova, M.S. Riedl, F.G. Williams, G.L. Wilcox and R. Elde. Effects of Peripheral Nerve Injury on Delta Opioid Receptor (DOR) Immunoreactivity in the Rat Spinal Cord. Neuroscience Letters 361(1-3):208-211, 2004.
L.S. Stone.and L. Vulchanova. The Pain of Antisense: in vivo Application of Antisense Oligonucleotides for Functional Genomics in Pain and Analgesia [Review]. Advanced Drug Delivery Reviews 55(8):929-1115, 2003.
L. Vulchanova, T.H. Olsen, L.S. Stone., M.S. Riedl, R. Elde and C.N. Honda. Cytotoxic Targeting of Isolectin Ib4-Binding Sensory Neurons. Neuroscience 108(1):143-155, 2001.
C.A. Fairbanks, I.J. Posthumus, K.F. Kitto, L.S. Stone.and G.L. Wilcox. Moxonidine, an a2/Imadazoline Receptor Agonist, Synergizes with Morphine and Deltorphin II to Inhibit Substance P-Induced Behavior in ICR Mice. Pain 84(1):1107-1116; 2000.
L.S. Stone., L. Vulchanova, M.S. Riedl, J. Wang, F.G. Williams, G.L. Wilcox, and R. Elde. Effects of Peripheral Nerve Injury on Alpha-2A and Alpha-2C Adrenergic Receptor Immunoreactivity in the Rat Spinal Cord. Neuroscience 93(4):1399-1407; 1999.
L. Vulchanova, M.S. Riedl, S.J. Shuster, L.S. Stone., K.M. Hargreaves, G. Buell, A. Surprenant, R.A. North and R. Elde. P2X3 is Expressed by DRG Neurons that Terminate in Inner Lamina II. European Journal of Neuroscience 10: 3470-3478; 1998.
L.S. Stone., C. Broberger, L. Vulchanova, G.L. Wilcox, T. Hökfelt, M. Riedl and R. Elde. Differential Distribution of Alpha-2A and Alpha-2C Adrenergic Receptor Immunoreactivity in the Rat Spinal Cord. Journal of Neuroscience, 18(15):5928-5937; 1998.
L.S. Stone., L. Macmillan, K.F. Kitto, L. Limbird and G.L. Wilcox. The a2a-Adrenergic Receptor Subtype Mediates Spinal Analgesia Evoked by a2-Agonists and is Necessary for Spinal Adrenergic/Opioid Synergy. Journal of Neuroscience, 17(18):7157-7165; 1997
L.S. Stone., C.A. Fairbanks, T.M. Laughlin, H.O. Nguyen, T.M. Bushy, M. Wessendorf and G.L. Wilcox. Spinal Analgesic Actions of the New Endogenous Opioid Peptides Endomorphin-1 and -2. Neuroreport 8(14):3131-3135; 1997.
J. Lai, M. Riedl, L.S. Stone., U. Arvidsson, E.J. Bilksy, G.L. Wilcox, R. Elde and F. Porreca. Immunofluorescence Analysis of Antisense Oligo-deoxynucleotide-Mediated Knock-Down’ of the d Opioid Receptor in Vitro an in Vivo. Neuroscience Letters 213:205-208; 1996.
C.A Fairbanks, L.S. Stone., and G.L Wilcox. Pharmacological Profiles of Alpha-2 Adrenergic Receptor Agonists Identified using Genetially Altered Mice and Isobolographic Analysis [Review] Pharmacology and Therapeutics, in press.
L.S. Stone. Joint degeneration and chronic pain: Still looking for the missing link (Editorial), Pain 141(1):185-186, 2009.
T. Ness, U. Wesselmann, L.S. Stone., P. Mantyh, J. Neubert. The American Pain Society and Translational Pain Research: A Position Statement from the American Pain Society. Copyright 2007 by the American Pain Society.
C. Bantel, L.S. Stone., M. Maze, G. L. Wilcox “Alpha2-Adrenergic Agonists in Pain Treatment” In: Schmidt, R.F, & Willis, W.D (eds). Encyclopedic Reference of Pain. Springer, Berlin Heidelberg New York, 2005.
G. L. Wilcox, L.S. Stone., M.H. Ossipov, J. Lai, F. Porreca “Pharmacology of pain transmission and modulation. I. Central mechanisms” In: M. Pappagallo (Ed.), The Neurologic Basis of Pain, McGraw-Hill, New York, pp. 31 -52; 2004.