Joel Castro Kraftchenko
School of Biomedicine
Faculty of Health and Medical Sciences
2015: Joel Castro (Kraftchenko) Research Officer
Visceral Pain Laboratory (SAHMRI)
Flinders University.
Dr. Joel Castro Kraftchenko (known as Joel Castro on its publication records) is a principal investigator and Head of the Endometriosis Research Unit at the Visceral Pain Research Group, located at the South Australian Health and Medical Research Institute (SAHMRI). He is an expert in the field of visceral nociception and pain and his research focuses on understanding the causes, and developing treatments, for chronic visceral pain associated with inflammatory diseases such as endometriosis, inflammatory bowel disorder (IBD), and irritable bowel syndrome (IBS). Dr. Castro’s research has contributed 62 peer-reviewed manuscripts in top ranked journals including Nature (x2), Cell, Nature Communication, Gastroenterology, Gut, PNAS, Pain, and JCI insight. Together these outputs have been cited over 4670 times (Google Scholar August 2024) with and h-index of 36. 65
Dr Castro’s research focuses on studying the sensory afferents innervating visceral organs, to understand how pain is detected from these sites. He investigates the ion channels/receptors expressed within these afferents (which govern their function); how these afferents are altered in animal models of endometriosis, IBD and IBS, and what changes in ion channel/receptor expression occur, to trigger these alterations and cause chronic visceral pain.
Throughout his career Dr. Castro has contributed to the establishment and characterisation of clinically relevant animal models of endometriosis, IBD and IBD in remission (IBS-like mouse). He has developed several techniques crucial to identify functional, structural, and molecular characteristics of sensory fibres innervating visceral organs in health and disease states. The knowledge gained through this work has enabled fundamental breakthroughs in the treatment of pain in IBD and IBS patients. For example, as part of a collaboration with Ironwood pharmaceuticals, we performed the pre-clinical studies to support approval by the FDA of Linaclotide, a drug designed to relieve chronic visceral pain in IBS patients with constipation (IBS-C). This was a breakthrough for the field and was the first newly approved first-in-class treatment for IBS-C for several years.
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Appointments
Date Position Institution name 2015 - ongoing NHMRC Postdoc Researcher (Academic B) University of Adelaide -
Language Competencies
Language Competency English Can peer review Spanish; Castilian Can peer review -
Education
Date Institution name Country Title 2005 - 2008 Flinders University Australia PhD -
Research Interests
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Journals
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Book Chapters
Year Citation 2023 Maddern, J., Brierley, S. M., & Castro, J. (2023). Pre-clinical Models of Endometriosis: A Focus on Chronic Pain. In Visceral Pain (pp. 209-222). Springer International Publishing.
2018 Harrington, A. M., Castro, J., Erickson, A., Grundy, L., & Brierley, S. M. (2018). Extrinsic Sensory Afferent Nerves Innervating the Gastrointestinal Tract in Health and Disease. In H. M. Said (Ed.), Physiology of the Gastrointestinal Tract: Sixth Edition (Vol. 1-2, pp. 387-418). United Kingdom: Academic Press.
Scopus202012 Hughes, P., Brierley, S., Castro Kraftchenko, J., Harrington, A., & Blackshaw, L. (2012). Experimental colitis models. In A. Szallasi, & T. Biro (Eds.), Methods in Pharmacology and Toxicology: TRP Channels in Drug Discovery, Volume II (Vol. 2, 1 ed., pp. 379-390). USA: Springer.
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Conference Papers
Year Citation 2021 Castro, J., Maddern, J., Garcia-Caraballo, S., Schober, G., Lindstrom, B., Schmiel, S., & Brierley, S. (2021). CANNABINOID RECEPTOR 2 (CB<sub>2</sub>) LOCALIZATION IN COLONIC TISSUE AND PRIMARY SENSORY DORSAL ROOT GANGLIA (DRG) NEURONS ISOLATED FROM RODENTS WITH COLITIS AND CHRONIC VISCERAL HYPERSENSITIVITY. In GASTROENTEROLOGY Vol. 160 (pp. S503-S504). ELECTR NETWORK: W B SAUNDERS CO-ELSEVIER INC. 2020 Castro, J., Maddern, J., Garcia-Caraballo, S., Schober, G., Lindstrom, B., Schmiel, S., & Brierley, S. (2020). CANNABINOID RECEPTOR EXPRESSION AND THE EFFECT OF OLORINAB, A PERIPHERALLY ACTING, HIGHLY SELECTIVE, FULL AGONIST OF THE CANNABINOID RECEPTOR 2 (CB<sub>2</sub>), IN RODENTS WITH COLITIS AND CHRONIC VISCERAL HYPERSENSITIVITY. In GASTROENTEROLOGY Vol. 158 (pp. S269). Austin, TX: W B SAUNDERS CO-ELSEVIER INC. 2020 Harrington, A., Garcia-Caraballo, S., Grundy, L., Castro, J., Hannig, G., & Brierley, S. (2020). CHRONIC INTRA-COLONIC LINACLOTIDE ADMINISTRATION ALTERS GLIAL ACTIVATION IN A MOUSE MODEL OF CHRONIC VISCERAL HYPERSENSITIVITY. In GASTROENTEROLOGY Vol. 158 (pp. S803). Austin, TX: W B SAUNDERS CO-ELSEVIER INC.
WoS12020 Castro, J., Maddern, J., Erickson, A., & Brierley, S. (2020). Co-morbidities of IBS: Role of voltage-gated sodium channels in mouse vaginal afferent mechanosensation and pain. In NEUROGASTROENTEROLOGY AND MOTILITY Vol. 32 (pp. 1 page). WILEY. 2019 Castro, J., Harrington, A., Maddern, J., Schober, G., Grundy, L. A., Ge, P., . . . Brierley, S. (2019). CHRONIC INTRACOLONIC ADMINISTRATION OF LINACLOTIDE INHIBITS NOCICEPTIVE SIGNALING IN A MOUSE MODEL OF CHRONIC VISCERAL HYPERSENSITIVITY. In GASTROENTEROLOGY Vol. 156 (pp. S570). San Diego, CA: W B SAUNDERS CO-ELSEVIER INC.
WoS22019 Grundy, L., Castro, J., Maddern, J., Harrington, A., Hannig, G., Ge, P., & Brierley, S. (2019). CHRONIC COLONIC ADMINISTRATION OF THE GUANYLATE CYCLASE-C AGONIST LINACLOTIDE ATTENUATES COLITIS INDUCED BLADDER AFFERENT HYPERACTIVITY. In GASTROENTEROLOGY Vol. 156 (pp. S363). San Diego, CA: W B SAUNDERS CO-ELSEVIER INC.
WoS12019 Castro, J., Maddern, J., Garcia-Caraballo, S., Lumsden, A. L., Lindstrom, B., Adams, J., & Brierley, S. (2019). OLORINAB (FORMERLY APD371), A PERIPHERALLY RESTRICTED, HIGHLY SELECTIVE, FULL AGONIST OF THE CANNABINOID RECEPTOR 2 (CB<sub>2</sub>), REDUCES VISCERAL HYPERSENSITIVITY IN ANIMAL MODELS. In GASTROENTEROLOGY Vol. 156 (pp. S382). San Diego, CA: W B SAUNDERS CO-ELSEVIER INC.
WoS42019 Castro, J., Maddern, J., Garcia-Caraballo, S., Lumsden, A., Lindstrom, B., Adams, J., & Brierley, S. M. (2019). Olorinab (APD371), a peripherally restricted, highly selective, full agonist of the cannabinoid receptor type 2 (CB<sub>2</sub>), reduces visceral hypersensitivity in animal models. In NEUROGASTROENTEROLOGY AND MOTILITY Vol. 31 (pp. 2 pages). WILEY. 2018 Uhlig, F., Grundy, L., Castro, J., Brierley, S. M., Foster, S. J., & Grundy, D. (2018). Identification of modulators of intestinal nerve activity from <i>Staphylococcus aureus</i>. In NEUROGASTROENTEROLOGY AND MOTILITY Vol. 30 (pp. 1 page). WILEY. 2018 Erickson, A., Garcia-Caraballo, S., Castro, J., Grundy, L., Rychkov, G., Vetter, I., . . . Brierley, S. (2018). Role of voltage-gated sodium channel isoforms in colon-innervating neurons in mice. In NEUROGASTROENTEROLOGY AND MOTILITY Vol. 30 (pp. 1 page). WILEY. 2018 Grundy, L., Castro, J., Harrington, A., Garcia-Caraballo, S., Maddern, J., Rychkov, G., & Brierley, S. (2018). Colitis-induced chronic colonic hypersensitivity induces cross organ sensitisation of bladder afferent pathways. In NEUROGASTROENTEROLOGY AND MOTILITY Vol. 30 (pp. 1 page). WILEY.
WoS12018 Brierley, S., Castro, J., Maddern, J., Garcia-Caraballo, S., Lindstrom, B., & Adams, J. (2018). APD371, a peripherally restricted, highly selective, full agonist of the Cannabinoid Receptor 2 (CB2), reduces colitis-induced visceral hypersensitivity in rats. In NEUROGASTROENTEROLOGY AND MOTILITY Vol. 30 (pp. 2 pages). WILEY. 2017 Grundy, L. A., Castro, J., Harrington, A., Peters, S., Feil, R., Miller, P., . . . Brierley, S. (2017). EXTRACELLULAR CGMP REDUCES THE EXCITABILITY OF SENSORY DORSAL ROOT GANGLION NEURONS VIA AN EXTRACELLULAR MECHANISM. In GASTROENTEROLOGY Vol. 152 (pp. S156). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC.
WoS12015 Castro, J., Harrington, A. M., Lieu, T., Garcia-Caraballo, S., Maddern, J., O'Donnell, T., . . . Brierley, S. M. (2015). A Visceral Representation of Itch: Identification 'Itch-Specific' Pruritogenic Mechanisms Within Colonic Sensory Pathways. In GASTROENTEROLOGY Vol. 148 (pp. S733). Washington, DC: W B SAUNDERS CO-ELSEVIER INC. 2015 Harrington, A. M., Castro, J., Garcia-Caraballo, S., Maddern, J., O'Donnell, T., Grundy, L., . . . Brierley, S. M. (2015). GC-C Agonists As Regulators of Visceral Sensation: Modulation of Mucosal Sensitivity via the Epithelial GC-C/cGMP Pathway. In GASTROENTEROLOGY Vol. 148 (pp. S732-S733). Washington, DC: W B SAUNDERS CO-ELSEVIER INC. 2015 Castro, J., Harrington, A. M., Garcia-Caraballo, S., Maddern, J., O'Donnell, T., Grundy, L., . . . Brierley, S. M. (2015). Chronic Activation of the GC-C/cGMP Pathway by Linaclotide Inhibits Ascending Nociceptive Pathways and Restores Aberrant Spinal Cord Signaling. In GASTROENTEROLOGY Vol. 148 (pp. S194). Washington, DC: W B SAUNDERS CO-ELSEVIER INC. 2014 Castro, J., Rychkov, G. Y., Ghetti, A., Harrington, A. M., Kurtz, C. B., Silos-Santiago, I., & Brierley, S. M. (2014). Extracellular Cyclic GMP (cGMP), the Downstream Mediator Released in Response to Linaclotide-Induced Activation of Guanylate Cyclase-C (GC-C), Reduces Excitability of Murine and Human Dorsal Root Ganglion (DRG) Neurons. In GASTROENTEROLOGY Vol. 146 (pp. S722). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC. 2014 Harrington, A. M., Castro, J., Garcia-Caraballo, S., Maddern, J., Craik, D., Adams, D. J., & Brierley, S. M. (2014). α-Conotoxin Vc1.1 Targets GABAB Receptors Modulating CaV2.2 and CaV2.3 Calcium Channels in Sensory Pathways Mediating Chronic Visceral Pain. In GASTROENTEROLOGY Vol. 146 (pp. S156). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC. 2013 Castro, J., Harrington, A. M., Mann, E. A., Cohen, M. B., Kurtz, C. B., Silos-Santiago, A., & Brierley, S. M. (2013). Mechanisms Underlying Linaclotide Induced Inhibition of Colonic Nociception. In GASTROENTEROLOGY Vol. 144 (pp. S134). Orlando, FL: W B SAUNDERS CO-ELSEVIER INC. 2013 Harrington, A. M., Castro, J., Young, R. L., Kurtz, C. B., Silos-Santiago, A., Nguyen, N. Q., . . . Brierley, S. M. (2013). Alterations in the Guanylate Cyclase-C/cGMP Pathway in Patients With Irritable Bowel Syndrome With Constipation. In GASTROENTEROLOGY Vol. 144 (pp. S59-S60). Orlando, FL: W B SAUNDERS CO-ELSEVIER INC. 2013 Hughes, P. A., Harrington, A. M., Castro, J., Isaacs, N. J., Moretta, M., Hicks, G. A., . . . Brierley, S. M. (2013). Increased Efficacy of the Peripherally-Restricted Selective Kappa-Opioid Receptor Agonist, Asimadoline, in Chronic Visceral Hypersensitivity. In GASTROENTEROLOGY Vol. 144 (pp. S934-S935). Orlando, FL: W B SAUNDERS CO-ELSEVIER INC. 2012 Castro, J., Harrington, A. M., Hughes, P. A., Martin, C., Silos-Santiago, A., Kurtz, C. B., . . . Brierley, S. M. (2012). Mechanism of Action for Linaclotide Induced Abdominal Pain Relief. In GASTROENTEROLOGY Vol. 142 (pp. S699). San Diego, CA: W B SAUNDERS CO-ELSEVIER INC.
WoS52012 Harrington, A. M., Brierley, S. M., Castro, J., Isaacs, N. J., & Blackshaw, L. A. (2012). Characterization of Dorsal Horn Neurons Activated by Noxious Colorectal Distension in Health and Chronic Visceral Hypersensitivity. In GASTROENTEROLOGY Vol. 142 (pp. S699). San Diego, CA: W B SAUNDERS CO-ELSEVIER INC. 2012 Castro, J., Harrington, A. M., Page, A. J., & Brierley, S. M. (2012). Downstream Signaling Pathways of Nitric Oxide Induced Modulation of Colonic Afferent Mechanosensitivity. In GASTROENTEROLOGY Vol. 142 (pp. S697). San Diego, CA: W B SAUNDERS CO-ELSEVIER INC. 2011 Castro, J., Martin, C., Hughes, P. A., Silos-Santiago, A., Kurtz, C. B., Blackshaw, L. A., & Brierley, S. M. (2011). A Novel Role of Cyclic GMP in Colonic Sensory Neurotransmission in Healthy and TNBS-Treated Mice. In GASTROENTEROLOGY Vol. 140 (pp. S538). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC.
WoS182011 Castro, J., Harrington, A., Hughes, P. A., Martin, C., Page, A. J., Blackshaw, L. A., & Brierley, S. M. (2011). Nitric Oxide Mechanism of Action on Visceral Nociceptors. In GASTROENTEROLOGY Vol. 140 (pp. S536). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC. 2011 Harrington, A., Brierley, S. M., Castro, J., Hughes, P. A., & Blackshaw, L. A. (2011). Identification of Colonic Afferent Central Terminals and Changes Following Colonic Inflammation. In GASTROENTEROLOGY Vol. 140 (pp. S131). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC. 2011 Castro, J., Balemba, O. B., Blackshaw, L. A., & Brierley, S. M. (2011). Garcinia Buchananii Bark Extract Inhibits Nociceptors, With Greater Efficacy During Inflammation. In GASTROENTEROLOGY Vol. 140 (pp. S866). Chicago, IL: W B SAUNDERS CO-ELSEVIER INC.
WoS72010 Hughes, P., Brierley, S., Harrington, A., Castro, J., Martin, C., & Blackshaw, L. (2010). Differential coupling of cytokine receptors to sensory neurons in health and post inflammation. In Proceedings Vol. 138 (pp. 136-137). W B SAUNDERS CO-ELSEVIER INC.
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Conference Items
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Preprint
Year Citation 2022 Castro, J., Maddern, J., Chow, C. Y., Tran, P., Vetter, I., King, G., & Brierley, S. (2022). The voltage-gated sodium channel Na<sub>V</sub>1.7 underlies endometriosis-associated chronic pelvic pain.
2022 Bayrer, J., Castro, J., Venkataraman, A., Touhara, K., Rossen, N., Morrie, R., . . . Julius, D. (2022). Gut Enterochromaffin Cells are Critical Drivers of Visceral Pain and Anxiety.
2020 Grundy, L., Caldwell, A., Garcia-Caraballo, S., Grundy, D., Spencer, N., Dong, X., . . . Brierley, S. (2020). Activation of MrgprA3 and MrgprC11 on bladder-innervating afferents induces peripheral and central hypersensitivity to bladder distension.
As a principal investigator:
- 2020-2024: NHMRC Ideas Grant APP1181448 (Castro, PI). “Decoding the pathophysiology of chronic pelvic pain associated with endometriosis and related visceral comorbidities”. Goal: Using clinically relevant models of endometriosis in combination with human samples, to identify novel mechanisms driving chronic pelvic pain in endometriosis.
- 2021-2022: Endometriosis Australia Foundation Research Grant (Castro, PI). “Identifying inflammatory mediators secreted by the endometrium of women with endometriosis, relevant to pain transmission from visceral organs”. Goal: Using clinically relevant models of endometriosis in combination with human samples, to identify novel mechanisms driving chronic pelvic pain in endometriosis.
- 2020-2021: Flinders Medical Foundation Grant as sole CIA (Castro, PI). “Developing a in vivo technique to investigate endometriosis-related chronic pelvic pain”. Goal: Seed grant to help developing an assay to measure the activity of sensory neurons within intact Dorsal Root Ganglia in vivo (intra-vital imaging)
As a Co-investigator:
- 2022-2024: Pain Management Grant with The Hospital Research Foundation Group (Wardill, Mrozik, Lynn, and Castro). “Does the gut microbiota play an important role in mediating the painful side effects of cancer treatment?”
- 2021-2022: Innovation Grant Scheme. Department of Obstetrics and Gynaecology, University of Melbourne CIs: Sarah Holdsworth-Carson, Dr Joel Castro, A/Prof Berin Boughton, Dr Jane Girling.
- 2020-2021: H.S and J.C Anderson Charitable Trust. Dr Jane Girling, A/Prof Rebecca Campbell, Dr Joel Castro, Dr Sarah Holdsworth-Carson
- 2010-present: Industry support from Ironwood Pharmaceuticals, to determine novel treatments for chronic abdominal pain associated with IBS.
Research Only
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Past Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2015 - 2019 External Supervisor Role of Voltage-gated Sodium Channel Isoforms in Electrophysiological Properties of Neurons Innervating the Viscera in Mice Doctor of Philosophy Doctorate Full Time Ms Andelain Erickson
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