BIOBANK OF BIOLOGICAL SAMPLES FROM CHRONIC PAIN PATIENTS FROM CANADIAN REGISTRIES AND SCREENING FOR MOLECULAR MARKERS

Leader(s): Luda Diatchenko
Institution(s)McGill University
Other Members: Quebec Pain Network

Creation of a biobank of biological samples, including DNA, RNA and plasma proteins, obtained from patients in the registries of SPOR Network grant partners. Samples will be used to identify molecular markers of the chronicity of pain conditions and their response to specific treatments.



Why was the study done?

The main purposes of this study are to better understand the reasons why some patients that suffer with pain get better (achieve pain relief) with certain treatments while others do not; why pain becomes a long-term problem for some people; and how to prevent it from becoming a long-term problem. To do so we are creating the Quebec Low Back Pain Biobank (QLBPB) a biobank of biological samples – blood and saliva - obtained from patients in the Registries of our SPOR grant partners and we are focusing on patients with Low Back Pain (LBP) and with neuropathic pain (NP). Blood samples are collected to obtain DNA, RNA, and protein from blood cells. Saliva samples are collected to extract DNA. DNA and RNA are molecules that contain our hereditary genetic information and that control the activities of our body and cells. Proteins are molecules that are produced from our DNA and RNA and that execute the activities of our body and cells. We will investigate if differences in the DNA, RNA and proteins can answer to our initial questions.

These discoveries could help us develop precision medicine, that is, a targeted medicine for specific subpopulations of patients.

Moreover the creation of the QLBP BIOBANK will enable future research on pain: the data collected from questionnaires as well as DNA, RNA, and/or protein stored in the QLBP BIOBANK once de-identified will be shared with other researchers that obtain approval by both the QLBP Steering Committee and the appropriate Ethics Review Board.

 

How was the study done?

The study is dived in two arms. The retrospective arm includes saliva samples collected from subjects enrolled in the Quebec Pain Registry (QPR) for whom the Registry contains information about their pain states at the time of their initial treatment and at 6 month follow up and for whom information on treatment response is available. We sent these patients a study package by mail containing a saliva collection kit (Oragene) that has been used for DNA purification, together with a short questionnaire on their current pain status and the Informed Consent Form. A participation fee of $30 has been recognized to subjects who sent back the study materials. We have sent 5823 study packages and we have recruited 1000 participants: 602 female and 398 male. DNA from 1000 samples has been extracted in house with our own resources and quality control and integrity analysis have been performed. The recruitment through the Quebec Pain registry started in 2018 and it’s completed; we are now contacting participants with chronic low back pain enrolled in the Quebec Low Back Pain Core Study.

The prospective arm includes DNA, RNA and plasma samples purified from the blood and saliva of subjects enrolled from the Quebec Low Back Pain Core Study. We are focusing on acute low back pain participants (pain for less then 3 months), chronic low back pain participants (pain for more than 3 months) and healthy controls (no chronic pain conditions); participants must attend a visit during which a certified research nurse draws blood, collects saliva and assists them while they complete some questionnaires online. Participants with acute low back pain are asked to attend a second visit after three months.

The targeted enrolment is 400 subjects: 200 chronic low back pain participants, 100 acute low back pain participants and 100 healthy controls. Up to now, before all clinical studies were put on hold due to the COVID-19 outbreak, we had recruited 97 participants with chronic low back pain (43 female, 54 male), 13 with acute low back pain (5 female, 8 male) and 22 healthy controls (12 female, 10 male).



What were the study results?

The study is still ongoing and, before the COVID-19 outbreak, we were aiming to complete the recruitment phase by June 2021. Now we don’t know when we will be able to resume the research activities. We hope by the end of next year to complete this phase and to start to analyze the data. We are really eager to understand why pain, in this case low back pain, became a long-term problem for some people while for other don’t.



Was a patient-partner involved with your study?

We had the chance to benefit form the advise of several patient-partners during all the phases of the study: during the design of both arms of the study patients-partners helped us writing some documents as the Informed Consent Forms to make them more user-friendly for the participant and suggested us the schedule to contact and to send reminders to participants. A patient-partner is a stable member of the Steering Committee of the Quebec Low Back Pain Consortium, a consortium of researchers, research coordinators and chronic pain perspective partners who are part of the Quebec Pain Research Network (QPRN) Low Back Pain (LBP) Strategic Initiative.



Recent Updates:
The study is still ongoing and, before the COVID-19 outbreak, we were aiming to complete the recruitment phase by June 2021.
Last updated: August 2020


Selected Publications:
  • Benavides R., Vsevolozhskaya O, Cattaneo S, Zaykin D, Brenton A, Parisien M, Verma V,   Khoury S, Gilron I, Diatchenko L. A functional polymorphism in the ABCB1 transporter predicts pharmacologic response to combination of nortriptyline and morphine in neuropathic pain patients. Pain. 2020 Mar; 161(3):619-629. PMID: 31738228
  • Ohrbach R, Slade GD, Bair E, Rathnayaka N, Diatchenko L, Greenspan JD, Maixner W, Fillingim RB. Premorbid and concurrent predictors of TMD onset and persistence. Eur J Pain. 2020 Jan;24(1):145-158. PMID: 31421009
  • Verma V, Khoury S, Parisien M, Cho C, Maixner W, Martin LJ, Diatchenko L. The dichotomous role of epiregulin in pain. Pain. 2020 Jan 7. [Epub ahead of print] PMID: 31917773
  • Millecamps M, Qun Shi X, Piltonen M, Echeverry S, Diatchenko L, Zhang J, Stone LS. The geriatric pain experience in mice: intact cutaneous thresholds but altered responses to tonic and chronic pain. Neurobiology of Aging, 31 December 2019, accepted
  • Pagé G, Lacasse A, Beaudet N, Choinière M, Deslauriers S, Diatchenko L, Dupuis L, Grégoire S, Hovey R, Leclair E, Leonard G, Beraldo Meloto C, Montagna F, Parent A, Rainville P, Roy J-S, Roy M, Ware MA, Wideman TH, Stone LS, the Quebec Back Pain Consortium. The Quebec Low Back Pain Study: a protocol for an innovative 2-tier provincial cohort. PAIN Reports: 2020 January/February (5, 1): e799.
  • Zorina-Lichtenwalter K, Maixner V, Diatchenko L. Detangling red hair from pain: phenotype-specific contributions from different genetic variants in melanocortin-1 receptor. Pain. 2019 Dec 11. [Epub ahead of print]. PMID: 31834199
  • Gentile ME, Li Y, Robertson A, Shah K, Fontes G, Kaufmann E, Polese B, Khan N, Parisien M, Munter HM, Mandl JN, Diatchenko L, Divangahi M, King IL. NK cell recruitment limits tissue damage during an enteric helminth infection. Mucosal Immunol. 2019 Nov 27. [Epub ahead of print] PMID: 31776431
  • Zhu C, Han Q, Samoshkin A, Convertino M, Linton A, Faison EM, Ji RR, Diatchenko L, Dokholyan NV. Stabilization of μ-opioid receptor facilitates its cellular translocation and signaling. Proteins. 2019 Oct; 87(10):878-884. PMID: 31141214.
  • Khoury S, Piltonen MH, Ton AT, Cole T, Samoshkin A, Smith SB, Belfer I, Slade GD, Fillingim RB, Greenspan JD, Ohrbach R, Maixner W, Neely GG, Serohijos AWR, Diatchenko L. A functional substitution in the L-aromatic amino acid decarboxylase enzyme worsens somatic symptoms via a serotonergic pathway. Ann Neurol. 2019 Aug; 86(2):168-180. PMID 31177555.
  • Beraldo Meloto C, Slade GD, Lichtenwalter RN, Bair E, Rathnayaka N, Diatchenko L, Greenspan JD, Maixner W, Fillingim RB, Ohrbach R. Clinical predictors of persistent temporomandibular disorder in people with first-onset temporomandibular disorder. JADA. 2019 July Vol. 150, Issue 7, 572:581 e10. PMID: 31248483
  • Upadhyay U, Zhuang GZ, Diatchenko L, Parisien M, Kang Y, Sarantopoulos KD, Martin ER, Smith SB, Maixner W, Levitt RC. Profound analgesia is associated with a truncated peptide resulting from tissue specific alternative splicing of DRG CA8-204 regulated by an exon-level cis-eQTL PLoS Genet. 2019 Jun 14;15(6):e1008226. PMID: 31199789
  • Bersellini Farinotti A., Wigerblad G., Nascimento D., Bas D.B, Morado Urbina C., Selva Nandakumar K., Sandor K., Xu B., Abdelmoaty S., Hunt M.A., Ängeby Möller K., Baharpoor A., Sinclair J., Jardemark K., Lanner J.T., Khmaladze I., Borm L.E., Zhang L., Wermeling F., Cragg M., Lengqvist J., Chabot-Doré A-J., Diachenko L., Belfer I., Collin M., Kultima K., Heyman B., Andrade Jimenez J.M., Codeluppi S., Holmdah R., Svensson C.I. Cartilage-binding antibodies induce pain through immune complex–mediated activation of neurons. JEM 06-13-2019, vol. 216 no. 8. PMID: 31196979.
  • Slade G. D., Rosen, J. D., Ohrbach, R., Greenspan, J. D., Fillingim, R. B., Parisien, M., Khoury, S., Diatchenko, L., Maixner, W., Bair, E. Anatomical selectivity in overlap of chronic facial and bodily pain. PAIN Reports: May/June 2019 - Volume 4 - Issue 3 - p e729.
  • Parisien M, Samoshkin A, Tansley SN, Piltonen MH, Martin LJ, El-Hachem N, Dagostino C, Allegri M, Mogil JS, Khoutorsky A, Diatchenko L. Genetic pathway analysis reveals a major role for extracellular matrix organization in inflammatory and neuropathic pain. Pain. 2019 Apr;160(4):932-944. PMID: 30763288.
  • Piltonen M, Parisien M, Grégoire S, Chabot-Doré AJ, Jafarnejad SM, Bérubé P, Djambazian H, Sladek R, Geneau G, Willett P, Stone LS, Shabalina SA, Diatchenko L. Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms. Mol Neurobiol. 2019 Apr;56(4):2855-2869 PMID: 30066306.