Chronic pathological pain arising from our internal (visceral) organs is a colossal global problem, affecting millions of patients with Irritable Bowel Syndrome, Inflammatory Bowel Disease and overactive bladder. Our group investigates the underlying causes of chronic visceral pain, and the development of new treatments. Using state of the art molecular, anatomical and functional approaches allows us to study mechanisms from the single cell through to in vivo and clinical studies.
These multi-faceted research programs have translated to high-impact publications in journal such as Nature, Nature Communications, Nature Reviews Gastroenterology and Hepatology, Gastroenterology, Gut, Pain and The Journal of Neuroscience.
Our group is funded by the National Health and Medical Research Council of Australia (NHMRC), The Australian Research Council (ARC), and research collaborations with numerous international industry partners, including Takeda Pharmaceuticals and Ironwood Pharmaceuticals.
As an indication of clinical translation our group, in collaboration with Ironwood Pharmaceuticals, identified the mechanism of pain relief of a new drug, linaclotide, in treating patients with Irritable Bowel Syndrome with Constipation (IBS-C). Linaclotide, a guanylate cyclase-C (GC-C) agonist is effective in relieving abdominal pain associated with IBS-C and is available and registered for use by IBS-C patients in the USA and Europe.
Castro J, Harrington AM, Garcia-Caraballo S, Maddern J, Grundy L, Zhang J, Page G, Miller P, Craik D, Adams DJ, Brierley SM (2017). α-conotoxin Vc1.1 inhibits human dorsal root ganglion neuroexcitability and mouse colonic nociception via GABAB receptors. Gut, pii: gutjnl-2015-310971. doi: 10.1136/gutjnl-2015-310971 (Epub ahead of print). (Impact factor 14.66)
Osteen JD, Herzig V, Gilchrist J, Emrick JJ, Zhang C, Wang X, Castro J, Garcia-Caraballo S, Grundy L, Rychkov GY, Weyer AD, Dekan Z, Undheim EAB, Alewood P, Stucky CL, Brierley S.M, Basbaum AI, Bosmans F, King GF, Julius D (2016). Subtype-selective spider toxins implicate Nav1.1 voltage-gated sodium channels in mechanical pain. Nature, 534(7608):494-9. (Impact factor 41.456)
Carstens BD, Berecki G, Daniel JT, Lee HS, Jackson KAV, Tae H-S, Sadegh M, Castro J, O’Donnell T, Deiteren A, Brierley SM, Craik DJ, Adams DJ, Clark RJ (2016). Structure-Activity Studies of Cysteine-Rich α-Conotoxins Targeting the GABAB Receptor Reveal a Minimal Functional Motif. Angew Chem Int Ed Engl., 55(15):4692-6. (Impact factor 11.26)
Brust A, Croker DE, Colless B, Ragnarsson-McGrath L, Andersson A, Palant E, Jain K, Garcia-Caraballo S, Castro J, Brierley SM, Alewood PF, Lewis RJ (2016). Conopeptide-derived κ-opioid agonists: design of potent, selective and metabolic stable dynorphine mimetics with anti-nociceptive properties. Journal of Medicinal Chemistry, 59(6):2381-95. (Impact factor 5.447)
Dantas de Araujo A, Mehdi Mobli M, Castro J, Harrington AM, Vetter I, Dekan Z, Muttenthaler M, Wan JJ, Lewis RJ, King GF, Brierley SM & Alewood PF (2014). Selenoether oxytocin analogues have analgesic properties in a mouse model of chronic abdominal pain. Nature Communications, 5:3165. (Impact factor 10.015)
Brierley SM and DR Linden (2014). Neuroplasticity and dysfunction after gastrointestinal inflammation. Nature Reviews Gastroenterology and Hepatology, 11(10):611-27. (Impact factor: 10.25)
Hughes PA, Castro J, Harrington AM, Issacs NJ, Moretta M, Hick GA, Urso D and Brierley SM (2013). Increased kappa-opioid receptor expression and function during chronic visceral hypersensitivity. Gut, 63(7):1199-200. (Impact factor 10.73)
Castro J, Harrington AM, Hughes PA, Martin CM, Ge P, Shea CM, Jin H, Jacobson S, Hannig G, Mann E, Cohen MB, MacDougall JE, Lavins BJ, Kurtz CB, Silos-Santiago I, Johnston JM, Currie MG, and Brierley SM (2013). Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic GMP. Gastroenterology, 145(6):1334-46. (Impact factor 12.81)
Hughes PA, Harrington AM, Castro J, Liebregts T, Adam B, Grasby DJ, Issacs NJ, Maldeniya L, Martin CM, Persson J, Andrews JM, Holtmann GJ, Blackshaw LA and Brierley SM (2013). Sensory neuro-immune interactions differ between IBS subtypes. Gut, 62(10):1456-65. (Impact factor 10.73)