María Florencia Coronel
Laboratorio de Dolor en Cáncer, Instituto de Investigaciones en Medicina Traslacional CONICET - Universidad Austral
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Symposia
OCT 19 | 9:00 - 11:00
Neuroscience and Translational Pain Research
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The symposium will present recent advances in modern neuroscience, ranging from studies in animal models to human clinical trials, in relation to research of the most common, debilitating, and often undertreated condition affecting human health: pain. In the first lecture, Dr. Eduardo Souza-Silva will review the neurobiology of musculoskeletal nociception and the sensory role of histamine, a biogenic vasodilator amine involved in biochemical processes of the immune response. Also, the evidence found so far to validate the existence of a potential analgesic mechanism involving peripheral activation in the knee joint will be presented. The second presentation by Dr. José Biurrun Manresa, will be centered onhuman surrogate models of nociception and pain, describing how the knowledge from animal experiments is translated into human research, focusing on the development and assessment of models for central sensitization. Afterwards, Dr. Margarita Calvo, will present recent clinical findings demonstrating that chronic cutaneous injury can lead to injury and dysfunction of the most distal part of small sensory fibres in a length-dependent distribution resulting in disabling neuropathic pain. Finally, Dr. Pablo Brumovsky will review the antiallodynic and anti-inflammatory effects of IMT504, an oligodeoxynucleotide with immunomodulatory , in various animal pain models, as well as in a phase I-II clinical trials.
Speakers
Antinociceptive effect of intra-articular histamine in rats
Eduardo Souza Silva
Universidade Federal de Santa Catarina
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Histamine is a biological amine that acts on 4 types of receptors (H1-H4). The sensory role of histamine has been attributed mainly to its actions on H1R in cutaneous tissue, being accepted as a mediator of hyperalgesia in inflammation. Evidence supporting the nociceptive role for histamine in skin tissue in some cases may have been overestimated due to the low selectivity of H1 antihistamines, histamine concentrations above what can be released per gram of skin tissue, histamine activity in tissue cells or even the ambiguity of the sensations of itching and pain in the skin tissue. Although it is found in synovial fluid in different conditions of arthritis, the role of histamine in inflammatory pain is poorly understood. Our results show that H1 antihistamines promote hyperalgesia and, conversely, histamine reduces inflammatory joint pain. We highlight strong evidence for the role of the spinal cord in the hyponociceptive action of joint histamine suggesting the possibility of a mechanism that could help the development of new pharmacological strategies for the treatment of clinically relevant pain that usually originates from joint structures.
Human surrogate models of pain
José Biurrun Manresa
Institute for Research and Development in Bioengineering and Bioinformatics, IBB-CONICET-UNER
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Clinical trials in pain patients are usually a costly and time-consuming process, and they always involve a degree of heterogeneity with regards to the factors that could potentially interact with the neurophysiological mechanisms under evaluation. Prior evaluation of the efficacy of new drugs or alternative methods for pain relief in surrogate models serve as an initial proof of concept and help improving study designs and defining relevant efficacy parameters in subsequent clinical trials. While animal models are useful to get a better understanding of the neurobiology and mechanisms involved in nociception, these findings often do not translate to patients with chronic pain conditions. Hence, surrogate models of nociception and pain in healthy volunteers are necessary to translate data from animals to humans. This talk will present a description of the most common human surrogate models, describing how the knowledge from animal experiments is translated into human research, with particular focus on the development and assessment of models for central sensitization.
Small fibre neuropathy secondary to skin damage
Margarita Calvo
Pontificia Universidad Católica de Chile
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Small fibre neuropathy (SFN) is a disease that affects exclusively the un myelinated or thinly myelinated sensory and autonomic fibres. The main symptom are pain, itch and dysautonomy. It complicates several common diseases, such as diabetes mellitus and HIV, and the associated pain contributes significantly to the morbidity of these diseases. SFN is the most common polyneuropathy with an estimated incidence of 11.7 cases/100,000/y. The neurobiology of SFN is not well understood, hindering the development of new treatments. SFN is diagnosed based on presence of symptoms (pain or itch), plus abnormal thermal sensation, and a reduction in the density of small fibers in the epidermis. Small fibers innervate the epidermis and convey thermosensation, nociception and itch from the skin through sensory peripheral nerves to the dorsal horn. SFN is believed to occur due to a specific type of axonal degeneration called “dying back”. Neurons with their axons degenerating become hyperexcitable as a consequence of altered gene expression and post-translational modification of voltage gated sodium and potassium channels, leading to severe pain or itch or both. The causes of SFN are only found in around 50% of patients at initial workout. In here we will show that a potentially important and frequently overlooked cause of SFN are chronic inflammatory skin conditions such as Recessive Dystrophic Epidermolysis Bullosa and Lichen simplex chronicus.
IMT504 and chronic pain: A “bench to bedside” tale
Pablo Brumovsky
Instituto de Investigaciones en Medicina Traslacional
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Chronic pain, caused either by inflammation or peripheral neuropathies, affects millions of patients around the World. Many of these patients remain undertreated, as most drugs currently available to control pain have limited efficacy and/or exert serious adverse effects. In recent times, the role of the immune system in the mechanisms of pain is receiving serious attention, also for the development of new therapeutic agents. IMT504 is an oligodeoxynucleotide (ODN) with immunomodulatory and tissue repair properties. Work in our laboratory for the past 15 years has exposed remarkable antiallodynic and anti-inflammatory effects in various animal pain models. In the present talk, we will review these effects and relate them to recent findings on the role of different types of immune cells and mesenchymal stem cells. This will be followed by an elaboration on the steps taken thus far in relation to the validation of IMT504 as a therapeutic agent for the treatment of inflammatory or neuropathic pain in humans, through the development of a phase I-II clinical trial.