2014 QNJPI Conference - Quebec Network of Junior - Rencontre du RQJID 2014
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2014 QNJPI Conference
Quebec Network of Junior
Pain Investigators
Rencontre du RQJID 2014
Réseau québécois des jeunes
investigateurs de la douleur
Welcome message from the QNJPI board
The QNJPI board is very pleased to welcome you to this annual meeting. Our newly
formed board of directors is composed of dynamic members from each University
of Quebec. Together, we track recent and cutting-edge advances in pain research while
working for the interest of our members. We are thrilled with the number of conference
registrants and the very high quality of abstracts submitted for both student talks and
poster presentations. We hope that this meeting will stimulate knowledge exchange
between our members as well as collaborations between Universities for a more dynamic
research. We look forward to meet you and discuss during the meeting.
Enjoy the conference!
QNJPI board members
Message de bienvenue des membres du comité du RQJID
Les membres du comité du RQJID sont très heureux de vous accueillir à cette conférence
annuelle. Nous avons un tout nouveau comité formé de membres dynamiques provenant
des différentes universités de la province pour mieux suivre le pouls de la recherche en
douleur au Québec et l’intérêt de ses membres. Nous sommes ravis du nombre de
personnes inscrites à la conférence et de la qualité des résumés soumis tant pour les
présentations orales que les affiches. Nous espérons que cette rencontre puisse stimuler le
partage de connaissances entre nos membres ainsi que les collaborations entre universités
pour une recherche plus dynamique. Nous avons très hâte de vous rencontrer et de
discuter durant la conférence.
Profitez bien de la conférence!
Les membres du comité du RQJID
2
Conference Attendees
Lauren Martin, Mcgill University
Ihab Daou, McGill University Kayla Bergeron-Vézina, Université de
Jérôme Côté, Université de Sherbrooke Sherbrooke
Hugues Petitjean, McGill University Valerie Bourassa, McGill University
Marc Bergeron, Université Laval Florence Pomares, McGill University
Isabel Plasencia Fernandez, Université Lydia Girard-Tremblay, Université de
Laval Sherbrooke
Élora Midavaine, Université de Sherbrooke Noosha Yousefpour, McGill University
Irina Kudrina, McGill University Behrang Sharif, McGill University
Beatriz Monteiro, Université de Montréal Samantha Locke, McGill University
Véronique Gougeon, Université de Jeongho Jang, McGill University
Sherbrooke Ariane Ballard, Université de Montréal
Louis-Etienne Lorenzo, Université Laval Marie-Lou Filiatrault, Université de
Sarah Rosen, McGill University Montréal
Tony Lim, McGill University Magali Millecamps, McGill University
Mélisange Roux, UdeS Robert Samberg, McGill University
Jean-Daniel Dubois, Université du Québec à Amalia Callado Pérez, Université Laval
Trois-Rivières Rebecca Price, McGill University
Feng Wang, Université Laval Bérengère Houzé, Université de Montréal
Hélène Beaudry, McGill University Stéphanie Grégoire, McGill University
Hichem Saidi, Université de Montréal Yue Ran Sun, McGill University
Catherine Ferland, McGill University Marc André Dansereau, Université de
Hazim Alkhani, McGill University Sherbrooke
Steven Cordeiro Matos, McGill University Louis Couturier, Université de Sherbrooke
Luca Posa, Université de Montréal Katerina Lichtenwalter, McGill University
Robert Bonin, Université Laval Yao Yao
Jimena Perez Sanchez, Université Laval Karim Nagi, Université de Montréal
Ali Khatibi, Université de Montréal Cecile de Vos, McGill University
Christelle Khadra, Université de Montréal Marjo Piltonen, McGill University
Claire Magnussen, McGill University Martin Guillot, Université de Sherbrooke
Gabrielle Pagé, Université de Montréal Caroline Arbour, Université de Montréal
3Schedule of Events
9:45 Coffee and Posters Set-up
10-:00-10:15 Opening Remarks
10:15-11:00 Invited Speaker
- Martin Guillot, Université de Sherbrooke
11:00-12:00 Posters Session
12:00-12:45 Oral Presentations
- Tony Lim, McGill University
- Robert Bonin, Université Laval
- Véronique Gougeon, Université de Sherbrooke
12:45-13:45 Lunch and Posters Session
13:45-14:45 Oral Presentations
- Ali Khatibi, Université de Montréal
- Florence Pomares, McGill University
- Louis Couturier, Université de Sherbrooke
- Behrang Sharif, McGill University
14:45-15:00 Coffee Break
15:00- 16:00 Round Table Discussion
16:00-16:15 Presentation Awards
16:15- 17:00 Invited Speaker
- Loren J. Martin, McGill University
17:00 Happy Hour
4Invited Speaker
Martin Guillot PhD, Université de Sherbrooke
Martin Guillot is a postdoctoral researcher in
neurophysiology under the supervision of Dr
Serge Marchand and Roger Lecomte at the
Research Center of the Centre Hospitalier
Universitaire de Sherbrooke. He studied
Veterinary Medicine at École nationale
vétérinaire de Toulouse, France (2005), obtained
a Veterinary Internship (small animals) diploma
(2006) and a Master of Veterinary Sciences
(2009) at University of Montreal. He also
performed a PhD (2014) in Veterinary
Sciences/Pharmacology in Dr Éric Troncy’s lab
dealing with osteoarthritis-associated pain in
cats. His PhD work leads to the first
characterization of a central sensitization
component in osteoarthritis-associated pain in cats. This work was recognize by several
distinctions and awards as an Alexander-Graham-Bell doctoral Scholarship from the
NSERC, a doctoral Scholarship from the CIHR – MENTOR Strategic Training Initiative,
the Vetoquinol Canada Award in Animal Aging Research and the Merial Canada Award
in Animal Pain Research. His postdoctoral research focuses on animal model of
osteoarthritis-associated pain and on conditioned pain modulation in humans. For this
work, Dr Guillot is supporting by a Scholarship for postdoctoral research from the
NSERC. Dr Guillot is involved in several pain networks, particularly he is the current
Treasurer of the International Association for the Study of Pain - Pain and Pain
Management in Non-Human Species Special Interest Group.
5Why your cat is so grumpy?
Characterising osteoarthritis-associated pain in cats
Guillot M1,2, Rialland P1, Klinck MP1, Moreau M1, Taylor PM3, Rousseau JA2, Beaudoin
J-F2, Chartrand G4, Pelletier JP5, Martel-Pelletier J5, de Guise JA4, Lecomte R2, Troncy
E1,5.
1. Research Group in Animal Pharmacology of Quebec, Faculty of Veterinary Medecine,
Université de Montréal, St-Hyacinthe, QC, Canada 2. Centre d'imagerie moléculaire de
Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke,
Sherbrooke, QC, Canada.3. Topcat Metrology, Gravel Head Farm, Downham Common,
Little Downham, Nr Ely, Cambridgeshire, United Kingdom. 4. Laboratoire de recherche
en imagerie et orthopédie, Research Center of the Université de Montréal Hospital
Centre; École de Technologie Supérieure, Université du Québec, QC, Canada.5.
Osteoarthritis Research Unit, University of Montreal Hospital Research Center
(CRCHUM), Notre-Dame Hospital, Montreal (QC)
Feline osteoarthritis prevalence increases with age, up to 80% in cats aged 11 years old
and more. Osteoarthritis is associated with chronic pain expressing as altered behaviour
and a decrease in mobility. Currently, there is no validated technique to evaluate
osteoarthritis-associated chronic pain in cats. This situation leads to an absence of
approved medication for the treatment of OA-associated chronic pain in cats.
Our hypothesis states that osteoarthritis-associated pain in cats is expressed as physical
disabilities, neurophysiologic changes, hypersensibility, which need to be assessed to
quantify adequately this pain and its impact on quality of life. Our objectives were 1) to
develop a cat adapted method to assess physical disabilities using kinematics, kinetics
and motor activity evaluations; 2) to describe functional and neurophysiologic changes
related to osteoarthritis-associated pain, and to test a non steroidal anti-inflammatory
based analgesic treatment.
Using objective chronic pain evaluation tools determined as sensitive and repeatable, we
characterized feline osteoarthritis-associated pain. Cats afflicted with osteoarthritis
presented lameness characterised by decreased joint amplitude, or decreased peak ground
reaction vertical force, and decreased motor activity. Using the two latter evaluations, we
demonstrated the efficacy of a non steroidal anti-inflammatory (meloxicam) to alleviate
osteoarthritis-associated pain. Moreover, using quantitative sensory testing and brain
functional imaging, we demonstrated for the first time, that osteoarthritis-associated pain
in cats led to central nervous system changes. Specially, cats afflicted with osteoarthritis
developed central sensitisation as indicated by a decreased von Frey withdrawal threshold
(a reflex evaluation), and also by a facilitated mechanical temporal summation (an
approach allowing to take into account affective and cognitive dimensions of pain). The
increase of brain metabolism in the secondary somatosensory cortex, thalamus and
6periaqueductal grey matter also highlighted the importance of pain chronicity related
changes.
Using an analgesic treatment built to alleviate osteoarthritis-associated pain will improve
cats quality of life, will help veterinarians, and will benefit owners who will retrieve an
active and social cat. Demonstrating both the importance of central sensitisation and
assessment of brain changes related to osteoarthritis-associated chronic pain using brain
functional imaging opens new research opportunities in cats (development and/or
validation of hypersensitivity related treatments), and humans (potential natural model of
osteoarthritis-associated pain).
7Invited speaker
Lauren J. Martin PhD, McGill University
Loren Martin received his PhD in
neuroscience from the University of Toronto
under the supervision of Dr. Beverley Orser.
While there, he studied the role of GABA A
receptor neurotransmission in the
neuroplasticity of learning and memory using
a genetic mouse model. He is currently a
postdoctoral fellow in the Pain Genetics
laboratory of Dr. Jeffrey Mogil at McGill
University. His current work aims to identify
novel roles for growth factor receptors in pain
processing and determine social factors that
modulate pain in both mice and humans. He
has published 25 journal articles from his
graduate and postdoctoral studies and has received numerous honours and awards
including postdoctoral fellowships from CIHR, NSERC and the Canadian Pain Society.
His work has appeared in journals such as Nature Neuroscience, Nature Methods and the
Journal of Neuroscience. In January, he will start as Assistant Professor in the
Department of Psychology at the University of Toronto Mississauga, where he will
integrate his memory and pain backgrounds to study the interplay between cognition and
pain.
Loren Martin will be starting a professorship at university of Toronto this January. He
will talk about his career path, and the steps he took to get a professorship.
8Student Talks
Vascular dysfunction after nerve injury causes endoneurial hypoxia and
neuropathic pain
Tony KY Lim, Xiang Q Shi, Julia M Johnson, Samuel David, Ji Zhang
Integrated Program in Neuroscience, McGill University
Background: All our traumatic injury models of neuropathic pain involve constriction of
peripheral nerve. Such injuries are expected to cause changes to the microvasculature
which could then result in a functional deficit in the ability of the microvasculature to
supply the nerve with nutrients and oxygen. Such a functional deficit could have
implications in our understanding of neuropathic pain mechanisms. Methods: The partial
sciatic nerve ligation mouse model of neuropathic pain was used. To detect hypoxia,
mice were administered hypoxyprobe-1. Structural alterations in the nerve were
characterized to support the observation of chronic hypoxia in the nerve following injury.
To physiologically antagonize hypoxia, animals were treated with hyperbaric oxygen.
Results: Hypoxyprobe-1 demonstrated that PSNL created a hypoxic area at the injury site
up to 3 days post-injury. After day 3, widespread hypoxia was observed in the distal
portion of the nerve. The size of the lumen of the blood vessels increased, suggesting
ongoing vascular dysfunction. Both hypoxia and nerve injury reduced Na+/K+ ATPase
levels. Treatment of the PSNL mice with hyperbaric oxygen resulted in an alleviation of
neuropathic pain behaviours, which provides functional evidence that hypoxia is involved
in the generation of neuropathic pain. Conclusions: In summary, we describe evidence of
an ongoing vascular pathology in PSNL mice, which has not been previously described in
traumatic peripheral neuropathy. This ongoing vascular pathology results in endoneurial
hypoxia, which in turn contributes to the generation of neuropathic pain.
9A spinal analogue of memory reconsolidation enables the reversal of
hyperalgesia
Robert P. Bonin & Yves De Koninck
Université Laval
The development of persistent pain through the sensitization of pain relays in the spinal
cord dorsal horn shares many mechanistic and phenotypic parallels with memory
formation. Memory reconsolidation, in which the reactivation of memories renders them
labile and susceptible to erasure by inhibition of protein synthesis, may thus be of
particular relevance to the treatment of persistent pain. Here we test the hypothesis that
the reactivation of sensitized pain pathways initiates a process similar to memory recall
and reconsolidation to render hyperalgesia labile and erasable. We find that both acute
and long-lasting mechanical hyperalgesia could be reversed after reactivation of the
sensitized pain pathway and the concomitant inhibition of spinal protein synthesis. This
process was dependent on the activation of spinal AMPA, NMDA, and NK1 receptors
during reactivation of the sensitized pain pathways, and on the activation of CaMKII and
ERK. Additionally, the activation of spinal AMPA or NMDA receptors without
peripheral stimulation was sufficient to render hyperalgesia labile, suggesting this process
was mediated by post-synaptic activation of dorsal horn neurons. In electrophysiological
experiments, synaptic LTP in the superficial dorsal horn, a cellular model of
hyperalgesia, was similarly rendered labile and reversible by reapplying the LTP
induction stimulus in the presence of the protein synthesis inhibitor anisomycin. These
findings provide the first demonstration of a reconsolidation-like phenomenon in spinal
pain processing pathways, suggesting that reconsolidation may exist more broadly
throughout the CNS than previously known. These findings may further provide a novel
therapeutic strategy for the treatment and erasure of persistent pain.
10Conditioned pain modulation (CPM) triggered by the affective
component of pain
Gougeon, V., Gaumond, I., Goffaux, P., Potvin, S., & Marchand, S.
Université de Sherbrooke
It has been demonstrated that the affective component of pain influence pain perception
as well as pain inhibition mechanisms. Recent studies have established that cortical areas
involved in the experience of pain are also engaged when an individual observe, imagine
or anticipate someone else in pain. This study aims to determine if the observation of
ourselves or a loved one in pain can activate conditioned pain modulation mechanisms
(CPM) without a noxious stimulation. Thirty healthy participants (15 couples)
participated in four experimental conditions (baseline, pain, self and spouse observation).
CPM was evaluated by comparing pain intensity produced by a 2 minutes thermal
stimulation before and after a cold pressor test (2 minutes at 20 or 7°C). Results
demonstrated that the observation of both ourselves or a loved one in pain can trigger
CPM response. Correlational analysis relates CPM efficacy to different psychological
factors according to different experimental settings. Moreover, the mechanisms
underlying this activation are different between men and women; empathy is a
contributing factor in women during the observation of their spouse in pain, but not for
men. Taken together, these results support the role of the affective component of pain in
CPM and provide a better understanding of its implication.
11Differential spinal and supraspinal modulation of responses to pain by
attention: the case of vicarious pain facilitation
Ali Khatibi, Pierre Rainville
Laboratory of research on neuropsychophysiology of pain, University of Montreal
Pain is recognized as a sensory experience with emotional dimension. This unpleasant
experience can be influenced by a number of modulatory mechanisms. It has been shown
that, observation of pain in the facial expression of other people results in facilitation of
observers’ responses to pain. Researchers have shown that this facilitation occurs at both
spinal (improved nociceptive flexion reflex; NFR) and supraspinal (increased pain
perception) levels. On the other hand, a number of other studies suggested that
manipulation of attention of observers can influence facilitation of their responses. We
were aimed to compare facilitation of responses by observation of pain in the faces of
other people at spinal and supraspinal levels. We recorded participants’ NFR while they
were observing dynamic painful (three levels of intensity: strong, moderate, mild) and
neutral facial expressions of other people. In Separate trials, they were asked to rate the
intensity of shown pain or to compare facial movements in the upper versus the lower
part of the face. After each painful stimulation, participants rated felt pain in that trial.
Findings revealed that although participants NFR and pain reports increased by
observation more intense painful expressions, their response at the spinal level (NFR)
was modulated by the attentional manipulation while at the supraspinal level there was no
indication of attentional modulation. These results suggest that low level reflexive
responses are more prone to get influence from attentional manipulation as compared to
responses to pain at higher cortical processing levels.
12Are brain grey matter decreases related to water content change in
fibromyalgia?
Pomares FB, Roy S, Feier N, Stikov N, Naso L, Ceko M, Fitzcharles MA, Schweinhardt
P
Alan Edwards Centre for Research on Pain and Faculty of Dentistry, McGill University
Fibromyalgia patients present cerebral grey matter volume decreases observed with
magnetic resonance imaging (MRI), which have been related to longer pain duration as
well as cognitive dysfunction, pointing to the consequences long-term pain might have on
the brain and its function. Standard MRI does not allow determining the histopathology
of grey matter changes, which could be caused by changes in neuronal density, neuronal
viability, glial cells, or water content. In this study we investigated grey matter alterations
in 29 post-menopausal women with fibromyalgia compared to 28 healthy controls with
voxel-based morphometry on T1-weighted MRI images. T1 relaxation times maps
reflecting water content in grey matter were computed from quantitative MRI sequences.
Water content changes were assessed with voxel-based relaxometry. Fibromyalgia
patients had decreased grey matter volume in the precuneus/posterior cingulate cortex,
insula, and inferior parietal lobule compared to controls. Water content was not different
between patients and controls in brain areas showing decreased grey matter volume with
voxel-based morphometry. Voxel-based relaxometry is a new technique investigating
differences in regional cortical water content between patients and controls. We did not
observe water content differences in areas of decreased grey matter volume,
demonstrating that water content is not an underlying cause of the measured grey matter
volume decreases in fibromyalgia.
13Conditioned pain modulation in children: a complex interaction of age
and sex
Louis Couturier, Sylvie Lafrenaye; Mélanie Morin; Serge Marchand
Université de Sherbrooke
INTRODUCTION: Conditioned pain modulation (CPM), a paradigm where a painful
stimulus triggers the inhibition of pain, has been suggested as a predictor of chronic pain.
However, little attention has been given to this phenomenon in children. METHODS: 54
healthy subjects aged between 7-17 yo (mean 12,2 ± 3,6 yo) were included. To assess
CPM, the test-stimulus consisted of a thermal stimulation lasting 120s at constant
temperature on the forearm. Conditioning stimulus was a cold pressor test (CPT) using
circulating water at 10°C. CPM is the difference of pain reported for the test-stimulus
before and after the conditioning stimulus, expressed in percentage. RESULTS: When all
participants were considered, CPM was only present for the first 30s of test-stimulus,
averaging 12,6 ± 48,3% (p=0,008). When only childrenOptogenetic interrogation of itch pathway in awake mice
Behrang Sharif, Philippe Séguéla
McGill University
Itch can be described as an unpleasant sensation which leads to scratching behavior or the
desire to scratch. Despite significant overlaps between this sensation and nociception, and
despite its clinical prevalence in many chronic conditions, research on itch remained
somewhat limited until the recent years. Lately, the development of optogenetics and its
improvements have endowed scientists with tools to investigate various unknowns of the
nervous system in vitro and in vivo. In this project, taking advantage of these state-of-the-
art genetic tools, we are investigating the underlying neurophysiological basis of itch
sensation and its relation to pain. Using a Cre recombination-based BAC transgenic
mouse line, excitatory opsins (ChR2) and inhibitory proton pumps (ArchT) are targeted
selectively to the surface of the recently characterized MrgprA3+ peripheral neurons,
shown to constitute a population of itch-specific afferents (Han et al., 2013). In vitro
electrophysiological recordings of dissociated DRG and trigeminal neurons has validated
the specificity of expression and photocurrent densities in MrgprA3+ neurons. In vivo
studies will follow these experiments to evaluate the behavioral responses to light-evoked
activation of this pruriceptive pathway. Behavioral assays are currently designed to
measure scratching activity, perceived aversion and sensitization.
15Posters Presentations
1- Light-induced analgesia in freely moving optogenetic mice
Ihab Daou, Ariel R. Ase, Jeffrey S. Wieskopf, Jeffrey S. Mogil, Philippe Séguéla
McGill University
Aim of Investigation: Noxious stimuli are encoded by primary afferent neurons,
particularly nociceptors. Interfering with the activity of their peripheral endings alters
nociceptive transduction, leading to modified pain perception. The goal of this study is to
develop a rodent model in which light-induced analgesia could be achieved through
optogenetic silencing of peripheral nociceptors. Methods: Taking advantage of the
Nav1.8-Cre recombinase driver line, we used a conditional genetic strategy to deliver the
proton pump Archeorhodopsin (Arch) to Nav1.8-positive nociceptors.
Immunohistological analysis was conducted to assess the cellular distribution of Arch-
EGFP in peripheral pain pathways. Patch clamp recordings were performed to evaluate
the functionality of Arch pumps in normal and sensitized cultured dorsal root ganglia
(DRG) neurons. Finally, thermal and mechanical sensitivities of freely moving Arch-
expressing mice were investigated under normal and inflammatory conditions, to assess
the analgesic potential of orange-yellow light in acute and chronic pain models. Results:
Histological characterization showed a strong and selective distribution of Arch-EGFP in
DRG, trigeminal ganglia, sciatic nerve, glabrous skin and dorsal horn of the spinal cord
indicating an efficient trafficking from Nav1.8+ nociceptive cell soma to central and
peripheral targets. Electrophysiological recordings in DRG neurons revealed significant
outward photocurrents and hyperpolarizations in response to orange-yellow light (589
nm) stimulation. These light-evoked hyperpolarizations were sufficiently large to block
electrically- as well as chemically (αβmeATP)-induced action potentials in Arch-
expressing neurons. The efficient and functional expression of Arch in the periphery
translated into light-mediated decrease of mechanical allodynia under zymosan- and
capsaicin-induced inflammatory conditions, with optical stimulation having no effect on
basal mechanical threshold. Thermal sensitivity of Arch-expressing mice will be
interrogated under normal and chronic conditions, to determine the analgesic potential of
orange-yellow light on the thermal modality. Conclusions: Our data provide evidence for
a novel analgesic model in which nociception is remotely and optically silenced in
awake, behaving transgenic mice. The non-invasive control of genetically-defined
populations of primary afferent neurons represents a useful approach to modulate sensory
input and has the potential to lead to the discovery of innovative optogenetic treatments
for intractable chronic pain in humans.
162- Three-dimensional reconstruction of synaptic relationship
between interneurons of dorsal horn of the spinal cord
Hugues Petitjean
Physiology departement Mcgill University
The dorsal horn of the spinal cord is the first central region where somatosensory
information is processed. A complex network of excitatory and inhibitory interneurons
integrates peripheral inputs before transferring them to supraspinal sites. How the
different elements of this network are interconnected is not well established. In this study,
we propose a quantification method to analyze the synaptic appositions from identified
inhibitory neurons to identified excitatory neurons. This method uses transgenic reporter
mice, immunostainning, confocal imaging and image processing using the IMARIS
software. Our method allows us to generate a 3-D reconstruction of neuronal processes
and detect close synaptic appositions inferior to 100nm. This approach enabled us to
establish the connectivity pattern of parvalbumin interneurons onto their excitatory
interneurons target. Furthermore, our results indicate that a single inhibitory interneuron
can perform appositions onto multiple target excitatory interneurons. By combining this
approach with behavioral experiments, we will examine whether interfering with this
pattern of connectivity impacts the processing of sensory information in the dorsal horn,
especially in the context of chronic neuropathic pain.
173- Chloride extrusion enhancers as novel therapeutics for
neurological diseases
Marc Bergeron, Martin Gagnon et Yves DeKoninck
Université Laval
The K+-Cl– cotransporter KCC2 is responsible for maintaining low Cl– concentration in
neurons of the central nervous system (CNS), essential for postsynaptic inhibition
through GABAA and glycine receptors. While no CNS disorders have been associated
with KCC2 mutations, loss of activity of this transporter has emerged as a key
mechanism underlying several neurological and psychiatric disorders including epilepsy,
motor spasticity, stress, anxiety, schizophrenia, morphine-induced hyperalgesia and
chronic pain. Recent reports indicate that enhancing KCC2 activity may be the favoured
therapeutic strategy to restore inhibition and normal function in pathological condition
involving impaired Cl– transport. We designed an assay for high-throughput screening in
HEK293 and NG108 cells to identify KCC2 activators. The assay led to the identification
of KCC2 activators that reduce [Cl–]i. Optimization of a first-in-class arylmethylidine
family of compounds resulted in a KCC2-selective analog (CLP257) that lowers [Cl–]i.
CLP257 restored impaired Cl– transport in neurons with diminished KCC2 activity. The
compound rescued KCC2 plasma membrane expression without affecting protein levels.
In vivo, the compound renormalised stimulus-evoked responses in spinal nociceptive
pathways sensitized after nerve injury and alleviated hypersensitivity in the PNI model.
Oral efficacy for analgesia equivalent to that of Pregabalin but without motor impairment
was achievable with a CLP257 prodrug. These data show for the first time that it is
possible to reverse BDNF- and PNI-induced KCC2 downregulation found in chronic pain
by modulating [Cl–]i through the molecule CLP257, which likely acts on post-
translational KCC2 regulation mechanisms rather than transcriptional ones. Finally, these
results validate KCC2 as a druggable target for CNS diseases.
184- Targeting CCL2/CCR2 signaling in the management of
metastatic bone pain
Élora Midavaine, Pascal Tétreault, David A. Barrière, Jean-Michel Longpré and Philippe
Sarret
Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke,
Québec, Canada
Bone cancer pain is a debilitating condition for patients coping with bone metastasis.
Over 50% of patients suffer from unsuccessful pain management. Targeting CCL2/CCR2
chemokine axis has been shown to be effective in relieving pain in neuropathic and
inflammatory pain models. Furthermore, the CCL2/CCR2 system promotes breast cancer
spread to bones and bone remodeling. The aim of the present study was thus to
investigate the relevance of targeting CCL2/CCR2 axis in bone cancer pain management.
Our research relies on a breast cancer bone metastasis model in Sprague-Dawley female
rats which consists in injecting 30 000 MRMT-1 mammary carcinoma cells into the
femur. We found by immunofluorescence staining that MRMT-1 cells endogenously
express both CCL2 and CCR2. µCT, MRI, and PET analysis showed a profound
disorganization of the trabecular bone architecture, which was associated with
osteoclast/osteoblast imbalance. Furthermore, tumor proliferation also led to glial cells
reactivity in the spinal cord. Real-time qRT-PCR showed decreases in CCL2 and CCR2
mRNA expression levels in the DRGs ipsilateral to the surgery, although levels remained
unchanged in the spinal cord. Tumor progression was accompanied by an increase of the
mechanical hypersensitivity, tumor-bearing rats displaying decreased paw withdrawal
thresholds at days 11 to 18 compared to sham animals. Acute intrathecal administration
of the CCR2 antagonist RS 504393 (25 µg/rat) was successful at alleviating mechanical
allodynia, reaching up to 48% of pain relief at day 14. Altogether, these results suggest
that the CCL2/CCR2 chemokine axis represents a promising target for treating cancer
patients with painful bone metastases.
195- Analgesic efficacy of tramadol administered orally for two weeks
in cats with naturally occurring osteoarthritis
BP Monteiro,1 MP Klinck,1,2 M Moreau,1,2 M Guillot,1,2 PVM Steagall,3 JP Pelletier,2
J Martel-Pelletier,2 D Gauvin1 & E Troncy1,2
1 GREPAQ (Animal Pharmacology Research Group of Quebec), University of Montreal,
Canada; 2 Osteoarthritis Research Unit, University of Montreal Hospital Centre, Canada;
3 Clinical Sciences, University of Montreal
This study aimed to evaluate the analgesic efficacy of tramadol in feline osteoarthritis
(OA), in a prospective randomized blinded placebo-controlled design. In Phase 1,
evaluations aimed to differentiate non-OA (n = 5) from OA (n = 15) cats (Guillot et al.
2013). In Phase 2, OA cats were orally administered placebo (PG; n = 7) or tramadol (3
mg kg-1 bid) (TG; n = 8) for 19 days. Evaluations were performed in OA and non-OA
cats (baseline: D0), and in OA cats after 2 weeks (W2) of treatment, and included: 1)
peak vertical force (PVF); 2) night-time motor activity (MA); 3) mechanical paw
withdrawal threshold (PWT) with electronic von Frey; 4) response to mechanical
temporal summation (RMTS) (Guillot et al. 2014). Data were analysed with mixed model
methods ( = 0.05). Phase 1: 1) PVF was higher in non-OA cats (p = 0.005); 2) Night
MA and 3) PWT were not different between groups; 4) RMTS was higher in non-OA
than OA cats (p < 0.0001). Phase 2: 1) PVF increased in both groups (p = 0.02); 2) MA
increased only in the TG (p = 0.001); 3) PWT increased only in TG (p = 0.05); 4) RMTS
increased in all cats in the TG, with a significant difference between PG and TG at W2 (p
= 0.02). Biomechanical alterations were diagnosed in OA cats with PVF. Night MA
increased in TG. Nociceptive hypersensitivity, quantified by RMTS (not PWT), was
evident in OA cats and was responsive to tramadol treatment.
206- Gephyrin clusters are absent from small diameter primary
afferent terminals despite the presence of GABA(A) receptors
Louis-Etienne Lorenzo1,2,3,4, Antoine G. Godin1,5, Feng Wang1, Manon St-Louis2,
Salvatore Carbonetto6, Paul W. Wiseman5,7, Alfredo Ribeiro-da-Silva2,4,8 and Yves De
Koninck1,2,3,4
1 Institut Universitaire de Santé Mentale de Québec, Québec, Québec G1J 2G3, Canada 2
Department of Pharmacology & Therapeutics, McGill University, Montréal, Québec,
H3G 1Y6, Canada 3 Département de Psychiatrie et Neurosciences, Université Laval,
Québec, Québec, G1K 7P4, Canada 4 Alan Edwards Center for Research of Pain, McGill
University, Montréal, Québec, H3A 0G1, Canada 5 Department of Physics, McGill
University, Montréal, Québec, H3A 2T8, Canada 6 McGill University Health Centre,
Montréal, Québec, H3G 1A4, Canada 7 Department of Chemistry, McGill University,
Montréal, Québec, H3A 2K6, Canada 8 Department of Anatomy and Cell Biology,
McGill University, Montréal, Québec, H3A 2B2, Canada
While both GABAA-receptors (GABAAR) and glycine-receptors (GlyR) play a role in
control of dorsal horn neuron excitability, their relative contribution to inhibition of small
diameter primary afferent terminals remains controversial. To address this, we designed
an approach for quantitative analyses of the distribution of GABAAR-subunits, GlyRα1-
subunit and their anchoring protein, gephyrin on terminals of rat spinal sensory afferents
identified by Calcitonin-Gene-Related-Peptide for peptidergic terminals and by Isolectin-
B4 for non-peptidergic terminals. The approach was designed for light microscopy,
which is compatible with mild fixation conditions necessary for immunodetection of
several of these antigens. An algorithm was designed to recognize structures with
dimensions similar to those of the microscope resolution. To avoid detecting false
colocalization, the latter was considered significant only if the degree of pixel overlap
exceeded that expected from randomly overlapping pixels given a hypergeometric
distribution. We found that both CGRP(+) and IB4(+) terminals were devoid of GlyRα1-
subunit and gephyrin. The α1GABAAR was also absent from these terminals. In contrast,
the GABAARα2/α3/α5 and β3 subunits were significantly expressed in both terminal
types, as other GABAAR-associated-proteins (α-Dystroglycan/Neuroligin-2/Collybistin-
2). Ultrastructural immunocytochemistry confirmed the presence of GABAARβ3-
subunits in small afferent terminals. Real-time quantitative-Polymerase Chain Reaction
confirmed the results of light microscopy immunochemical analysis. These results
indicate that dorsal horn inhibitory synapses follow different rules of organization at pre
vs. postsynaptic sites (nociceptive afferent terminals vs. inhibitory synapses on dorsal
horn neurons). The absence of gephyrin clusters from primary afferent terminals suggests
a more diffuse mode of GABAA-mediated transmission at pre- than at postsynaptic sites.
217- Complete Reversal of Neuropathic and Inflammatory Mechanical
Allodynia in Pregnant Mice
Sarah Rosen, Jean-Sebastien Austin, Jeffrey S. Mogil
McGill University
We have recently observed that administration of intrathecal glial inhibitors only reverse
neuropathic and inflammatory mechanical allodynia in male mice, and have no effect in
female mice. We have collected evidence suggesting that whereas male mice employ a
microglia-dependent mechanism to mediate allodynia, and female mice instead employ T
cells to the same ends. A possible explanation for this sex difference is that males and
females have different T cell immune environments: males have a Th2-dominant and
females a Th1-dominant immune environment. However, during pregnancy, due to
changes in sex hormone levels, females shift to a Th2-dominant immune environment.
We wished to investigate the implications of this for microglia-dependence of mechanical
allodynia. We show here that pregnant female mice do indeed switch to a microglia-
dependent mechanism to mediate allodynia. In addition, we observe that in late
pregnancy female mice that once suffered from a neuropathic injury have little to no
evidence of pain. Female mice with spared nerve injury (SNI) or injected with complete
Freund's adjuvant (CFA) progressively lose mechanical allodynia during pregnancy;
shortly after delivery the mechanical allodynia returns to pre-pregnancy levels. This
phenomenon has been reported clinically, but has never been studied in animal models.
Current experiments are examining the role of gonadal hormones, T-helper cells, and
opioid receptors in these phenomena. Here we show that T-cell deficient, nude pregnant
mice do not exhibit a blockade of mechanical allodynia during late pregnancy after SNI,
suggesting that T-cells are playing a significant role in the phenomenon.
228- Novel antisense technology-based drugs for the targeted
treatment of pain: Proof-of-concept with the NTS2 receptor in a
context of acute and persistent pain
Mélisange Roux1, Pascal Tétreault1, Jean-Michel Longpré1, Ashley M. Jacobi2, Scott D.
Rose2, Mark A. Behlke2, Philippe Sarret1
1 Département de Physiologie et biophysique, Faculté de médecine et des sciences de la
santé, Université de Sherbrooke, Sherbrooke, Qc, Canada. 2 Integrated DNA
Technologies Inc., Coralville, IA, USA.
Activation of the neurotensin receptor 2 (NTS2) modulates the spinal nociceptive
transmission. To open up new therapeutic approaches towards enhancing pain treatment,
we develop here a gene therapy based on a novel antisense technology. Small interfering
RNA (siRNA) requires to be complexed to a transfection agent, which provokes
undesired effects in vivo, like inflammatory responses. In fact, transfection agents are
frequently toxic for the organism and restrict the amount of interfering molecules to be
injected thus limiting their effectiveness. In this study, we demonstrate that NTS2-
specific antisense oligonucleotides (ASO) containing locked nucleic acid modifications
(LNA) can be injected solely in the central nervous system of SD rats to decrease the
antinociceptive action of a NTS2-selective agonist without causing any adverse effects.
An in vitro screening enabled us to select two ASO-LNA sequences with best efficacies
to reduce NTS2 expression. We then confirmed by confocal microscopy the capacity of
ASO-LNA to penetrate rat dorsal root ganglion neurons after intrathecal injection (i.t)
with a Texas Red-labeled sequence. Two NTS2-selective ASO-LNAs were tested for
their ability at reducing the antinociceptive response produced by JMV-431, a NTS2-
selective agonist. In the tail-flick test, only one ASO-LNA was able to completely reverse
the JMV-431 antinociceptive effect, indicative of a knockdown of NTS2. Interestingly,
both NTS2-ASO-LNA candidates abolished JMV-431 antinociception in the persistent
pain model. Overall, ASO-LNA represents a promising and secure alternative to
pharmacological approaches for studying and eventually treating central nervous system
pathologies, including pain.
239- Contribution of TRPC3 to calcium homeostasis and inflammatory
nociceptive pathways in DRG sensory neurons
Hazim Alkhani, Ariel R. Ase, Rebecca Grant, Dajan O’Donnell, Philippe A. Seguela
McGill University
Pain is an unpleasant sensation experienced following peripheral injury, inflammation or
ischemia. Pathologically abnormal calcium levels in peripheral DRG neurons are linked
to sensory hyperexcitability and chronic pain. Tight regulation of extracellular calcium
entry is key to calcium homeostasis and STIM1-dependent SOCE (store-operated
calcium entry) has been implicated as a major mechanism for regulating intracellular
calcium levels. The TRPC (transient receptor potential, canonical) gene family encodes 7
subunits assembled in tetrameric calcium-permeable channels at the plasma membrane.
TRPC channels have a documented role in both store- and receptor-operated responses
linked to phospholipase C, a key pathway in inflammatory sensitization of DRG neurons.
Our in situ hybridization data on the distribution of the entire TRPC family at the cellular
level showed that TRPC3 is strongly expressed in adult rat DRG sensory neurons,
particularly in small and medium diameter nociceptors. Using ratiometric calcium
imaging, pharmacology, gene knockdown and overexpression, we gathered evidence for
a significant involvement of TRPC3 in both store- and GqPCR-operated channels in
recombinant preparations as well as in rat DRG neurons. Overexpression of TRPC3 in rat
DRG neurons resulted in a strong increase of calcium influx upon endoplasmic reticulum
(ER) store depletion with thapsigargin, implicating the channel’s role in SOCE. This was
complemented with shRNA-mediated knockdown, where we measured a significant
decrease in calcium entry following ER store depletion, which was also confirmed with a
TRPC3 specific blocker, Pyrazole-10. Furthermore, a functional link with the
inflammatory metabotropic receptors P2Y2 and PAR2 was also observed with our
overexpression and knockdown assays. Our results indicate that TRPC3 contributes to
sensory neuron excitability through a dual role: by participating in STIM1-dependent
calcium homeostasis and by linking the activation of inflammatory receptors to the
recruitment of calcium-dependent signalling pathways.
2410- A role for noradrenergic modulation of HCN channels in
neuropathy-associated hyperexcitability of the medial prefrontal
cortex
Steven Cordeiro Matos, Geraldine Longo, Zizhen Zhang, Alfredo Ribeiro-da-Silva and
Philippe Seguela
McGill University
It is well established that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate a
variety of critical neuronal properties. Moreover, cationic currents mediated by HCN channels (Ih) play a
role in peripheral pain pathways by facilitating ectopic firing and hyperexcitability. Consistently, mice in
which HCN2 channels were selectively deleted in Nav1.8-positive DRG nociceptors showed no
neuropathic pain in response to mechanical and thermal stimuli. However, little is known regarding the role
of Ih in supraspinal pain pathways, particularly the medial prefrontal cortex (mPFC). The mPFC is
involved in affective aspects of pain and exhibits high HCN channel expression. Our primary aim is to
provide novel insights into the involvement of Ih in pain processing and the underlying mechanisms in the
neuropathic mPFC. To investigate the effect of nerve injury on HCN channel function, we used the rat
spared nerve injury (SNI) model of chronic neuropathic pain and whole-cell patch-clamp recordings in
layer II/III pyramidal neurons in acute mPFC slices. The von Frey, Hargreaves and acetone tests were
performed on naive, sham-operated and SNI rats to determine the development of neuropathic pain in the
SNI group at 3 weeks post-surgery. Immunofluorescence experiments were performed on tissue extracted
from perfused sham and SNI rats to determine changes in noradrenergic fiber density in the mPFC. SNI
rats displayed lower thresholds for nocifensive responses to mechanical and thermal stimuli, consistent
with the development of neuropathic pain. In contralateral mPFC slices, we observed a hyperpolarizing
shift in the voltage-dependent activation of HCN channels in SNI pyramidal neurons. Consistently, SNI
neurons exhibited both increased input resistance and excitability compared to sham neurons. However, the
amplitude and density of maximal Ih were not significantly different between both groups. We previously
observed that HCN channels modulate mGluR5-mediated persistent firing (PF), a cellular substrate for
working memory, in layer II/III pyramidal neurons of the mPFC and that norepinephrine (NE) enhances PF
via postsynaptic 2 adrenoceptor-mediated HCN channel inhibition. Interestingly, when we applied
subthreshold doses of the group 1 mGluR agonist DHPG, some PF was evoked in SNI but not in sham
pyramidal neurons. Hence, this phenomenon may contribute to pain processing in the context of nerve
injury-related mnemonic processes and/or attention to pain. Furthermore, preliminary data show that
application of bromo-cAMP is capable of shifting the activation curve of HCN channels to more
depolarized potentials in SNI neurons, suggesting that altered cAMP regulation might underlie the
hyperpolarizing shift observed in SNI conditions. Application of the 2 agonist clonidine induces a similar
hyperpolarizing shift in the voltage-dependent activation of HCN channels. Interestingly, we also observed
an increased density of noradrenergic fibers in the mPFC of SNI rats. This suggests that noradrenergic
modulation plays a significant role in the changes to HCN channel properties observed in SNI neurons. Our
findings suggest that the hyperpolarizing shift in the voltage-dependent activation of HCN channels
observed in SNI prefrontal neurons might arise from a decrease in cAMP levels mediated by abnormal 2
adrenoceptor activation. Thus, we propose a model in which high levels of NE in the mPFC, linked to pain-
associated stress, promote HCN channel-dependent hyperexcitability that contributes to the manifestation
of neuropathic pain.
2511- Molecular determinants of delta opioid receptor recycling
Luca Posa¹, Iness Charfi¹ and Graciela Pineyro¹²
¹Department of Pharmacology, University of Montreal, ²Department of Psychiatry,
University of Montreal
Opioids are the most potent analgesics for the treatment of severe pain. Delta opioid
receptor (DOR) agonists induce their analgesic actions with fewer side effects than those
of mu receptor, making them a target of interest for development of novel analgesics.
However, chronic use of DOR agonists induces analgesic tolerance. Recent hypotheses
suggest that the distinct profiles of tolerance of different opioid analgesics could result
from the stabilization of different ligand-specific conformations of the receptor, each
having different trafficking profiles. We compared different DOR ligands to assess
whether they display different post-endocytic trafficking properties. Experiments were
done in cortical neurons and HEK293 cells transfected with DORs. Our results indicate
that in neurons, DPDPE, UFP-512 and TIPP were able to induce DOR recycling, while
SNC-80 and morphine did not. We observed that when stimulated by DPDPE, DORs co-
localize with mannose-6-phosphate receptors (M6PR), a marker for late endosomes (LE)
and the trans-Golgi network (TGN). Inhibition of Rab9 and TIP47 (two proteins involved
in the transport between LE and TGN) affects DOR recycling. Taken together, in neurons
translocation from LE to TGN constitutes a route for internalized DORs to reach the
membrane. In HEK293 cells, only DPDPE stimulation triggered the receptor to enter into
the recycling pathway. Here too, DORs co-localized with M6PR and recycling was
dependent on Rab9 and TIP47. Furthermore, the kinase PKD (which is known to
intervene in trafficking from TGN to the membrane), Rab7 (which enables retromer-
mediated transport from sorting endosomes (SE) to TGN) and Rab11 (which mobilizes
recycling cargo from perinuclear compartment to the membrane) were also involved in
this process. We can conclude that in HEK293 cells, the DOR may recycle from the SE
directly or via the LE and/or the TGN. These results will help towards the development
of ligands with a longer analgesic activity.
2612- α5GABA-A receptors in the superficial dorsal horn regulate
central sensitization
Perez-Sanchez J, Bonin RP, Lorenzo LE, Labrakakis C, Bridgewater E, Orser BA, De
Koninck Y
Université Laval
The tonic activation of extrasynaptic α5 subunit-containing GABA-A (α5GABA-A)
receptors is known to regulate neuronal excitability in the CNS. In the spinal cord, tonic
inhibition may be important for the control of nociception and has been suggested to
contribute to hyperalgesia. However, the role of α5GABA-A receptors in nociceptive
information processing remains elusive. We therefore explored the distribution of
α5GABA-A receptors in the dorsal horn of the spinal cord and their functional
contribution to pain processing. Immunohistochemical analysis showed that α5GABA-A
receptors are localized in superficial layers in the dorsal horn of the spinal cord. Thus, we
recorded from dorsal horn neurons located in laminae I and II from Gabra5−/− and wild
type (WT) mice. We found no change in either frequency or amplitude of miniature
inhibitory postsynaptic currents (mIPSCs), consistent with the extrasynaptic nature of
these receptors. Tonic current, measured by the administration of bicuculline, was
decreased in lamina II cells of Gabra5−/− mice. In behavioural tests, mice lacking the
α5GABA-A receptors (Gabra5−/−) exhibited increased responses in phase 2 of the
formalin test, which has been associated with central sensitization in the dorsal horn.
However, no difference was found in the mechanical hyperalgesia produced by
intraplantar administration of capsaicin between Gabra5−/− and WT mice. Also, baseline
acute nociception was similar between Gabra5−/− and WT mice. Taken together, our
data suggest that α5GABA-A receptors contribute to central sensitization in the dorsal
horn of the spinal cord in a modality specific manner.
2713- Évaluation de l'efficacité d'interventions de distraction virtuelle
pour la gestion de la douleur procédurale et de l’anxiété d’enfants ayant
subi des brûlures
Christelle Khadra & Sylvie Le May, PhD
Université de Montréal
Problématique: La douleur procédurale reste la douleur la plus intense et le plus souvent
sous-traitée parmi les douleurs associées aux brûlures. Pour soulager cette douleur, les
méthodes habituelles consistent surtout en l’administration d’analgésiques et
d'anxiolytiques. Mais leur usage n’assure pas toujours un soulagement optimal et il est
souvent accompagné d’effets secondaires. D’où l’importance d’une approche
multimodale combinant la médication et une intervention non-pharmacologique telle que
la distraction. La distraction par réalité virtuelle (RV) permet de détourner la
concentration de l’enfant vers un élément attrayant, entravant sa perception des stimuli
douloureux. But: Le but de l'étude sera donc d'évaluer l’efficacité de la distraction (RV)
combinée aux analgésiques pour le soulagement de la douleur procédurale et de l’anxiété
d’enfants ayant subi des brûlures et la réduction du besoin en opioïdes. Méthode: ECR
auprès d'enfants francophones de 2 à 17 ans ayant subi des brûlures et nécessitant un
débridement de leurs plaies. Taille de l’échantillon souhaitée: 66 patients. Milieux : Deux
centres hospitaliers universitaires pédiatriques de la région de Montréal. Allocation :
selon une liste randomisée préétablie, groupe expérimental (traitement standard
+intervention de distraction par RV), groupe contrôle (traitement standard). Plan
d’analyses : des analyses quantitatives multivariées et des comparaisons entre les deux
groupes selon les deux variables dépendantes principales seront effectuées pour
déterminer l’efficacité de l’intervention. Retombées escomptées: la distraction par la
réalité virtuelle pourrait constituer un moyen non pharmacologique important pour
soulager la douleur, sans effets secondaires et facile à utiliser dans les unités des Grands
Brûlés.
2814- Neuropeptide Y is abundantly expressed in the peripheral nervous
system in a rat model of trigeminal neuropathic pain
Magnussen, C.; Hung, SP.; Ribeiro-da-Silva, A.
McGill University
Neuropeptide Tyrosine (NPY) is a neurotransmitter implicated in the modulation of pain.
Normally, NPY is found in interneurons in the dorsal horn of the spinal cord and in
sympathetic neurons but is absent from the cell bodies of sensory neurons. While NPY is
upregulated in the CNS after nerve injury, NPY expression in the periphery has never
been investigated in a pain model. NPY expression in the trigeminal ganglia (TG), the
mental nerve (MN) and in the skin of the lower lip was studied in relation to markers of
sensory and sympathetic fibers to determine in which populations of fibers NPY was
upregulated in following a chronic constriction injury (CCI) of the mental nerve. CCI rats
developed mechanical allodynia, which was present at 2 and 6 weeks. NPY-
immunoreactivity (IR), not seen in control TG cell bodies, was significantly upregulated
2 and 6 weeks after CCI in medium to large diameter TG neurons expressing NF200, but
not CGRP. NPY fibers, absent from the MN of controls, were seen both proximal and
distal to the ligations. In the skin, CCI caused a sprouting of sympathetic fibers into the
upper dermis, a region from where they are normally absent, and these fibres contained
NPY. In addition, some sensory neurons in the skin began to express NPY after CCI.
This is the first study to detail changes in NPY expression in the periphery in a pain
model.
2915- Tracking the pain trajectory of patients treated in tertiary care
multidisciplinary pain treatment facilities using the Quebec Pain
Registry database
Pagé, Gabrielle(1); Ware, Mark(2); Romero Escobar, Edwin Manolo(3); Choinière,
Manon(1)
(1) Centre de recherche du Centre hospitalier de l'Université de Montréal; (2) Alan
Edwards Center for Research on Pain - McGill University; (3) Department of
Psychology, York University
Objectives: The heterogeneity of pain experiences is often neglected when using
statistical approaches that use average pain scores across patient groups. The goals of the
present study were to 1) identify subgroups of patients that shared similar pain intensity
trajectories over the first 24 months of attending a multidisciplinary pain treatment
facility (MPTF), and 2) examine how these trajectories were associated with various pain
and psychological outcomes at 24-months. Methods: Participants were 2540 patients
(mean age = 53.45 (SD = 14.2); female = 60.2% [n = 1530]) attending one of three
MPTFs and enrolled in the Quebec Pain Registry. Patients completed a battery of
questionnaires on pain and psychosocial constructs before initiating treatment and at 6,
12, and 24 months thereafter. Data were analyzed using heterogeneous linear mixed
effects approach and MANOVAs. Results: Results showed a 6-trajectory model best fit
the data. Approximately 8% of patients reported a significant improvement in their pain
intensity levels, 22% reported stable mild-moderate pain intensity, while 70% reported
stable severe pain intensity. Pain trajectory membership predicted several pain
characteristics and psychological variables at 24 months. Implications: The results
revealed the presence of different subgroups of patients that differed in terms of initial
pain intensity and its rates of change over time. These pain trajectories were associated
with pain and psychological outcomes at 24 months. Early identification of patients in
poor outcome trajectories, through examination of baseline characteristics and rates of
change in pain scores, can provide valuable information about prognosis.
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