University of Texas System Hosts Pain Conference, Announces Formation of Texas Pain Research Consortium
This report was co-authored by Shivani Ruparel, University of Texas Health Science Center, San Antonio.
The University of Texas System and the University of Texas at Dallas (UTD) sponsored its very first pain research conference August 5-6, 2015, hosted by the UTD School of Behavioral and Brain Sciences. The two-day meeting, titled Advancing Pain Neuroscience Discovery Toward Therapeutics, was organized by Ted Price and Greg Dussor, and comprised over 140 faculty and postdoctoral, graduate, and undergraduate trainees representing pain research from 21 different organizations from across Texas. Twenty-seven pain researchers spanning 13 Texas universities data blitzed their latest discoveries, and 34 research posters were presented, evidencing the impressive scope of pain research currently occurring in Texas.
The meeting commenced by Ted Price and Greg Dussor from UTD welcoming the attendees, followed by the interim president of UTD, B. Hobson Wildenthal expressing his enthusiasm and support for the pain research efforts of Texas scientists. Invited keynote speaker, Rob Gereau, Washington University, St Louis, US, kicked off the meeting by highlighting the importance of translational science in advancing pain therapeutics and presented evidence supporting nociceptor sensitization by inflammatory mediators in human dorsal root ganglia (DRG) neurons. Pat Dougherty, MD Anderson, Houston, reiterated the importance of translational pain research and utilization of human tissues while presenting his recent work on the role of the Toll-4 receptor in chemotherapy-induced peripheral neuropathy (CIPN). Pradipta Ray, UTD, shared newly collected data, in collaboration with Ted Price and Greg Dussor, about pain transcriptomics. Using RNA-seq, they have analyzed human DRG from three pain patients so far and have found consistent dysregulation of various genes known to be involved in pain. Presenting a proposal for collaboration, Tae Hoon Kim, UTD, highlighted the potential for studying enhancer RNAs as a novel pain therapeutic target.
Terry Walters, University of Texas Health Science Center, Houston, chaired a session continuing the discussion of nociceptors driving persistent pain and central sensitization. He highlighted the occurrence of nociceptor sensitization across the animal kingdom from fruit flies and marine mollusks to mammals and discussed recent data on the role of Nav1.8 in the maintenance of pain following spinal cord injury. His talk was followed by that of Ken Hargreaves, University of Texas Health Science Center, San Antonio, discussing his research program analyzing TRP channels as integrators of lipid signaling pathways. He reported recent data indicating that inhibitors of oxidized lipids can reverse NGF-evoked persistent pain behaviors in a rodent model. The session continued with Yang Xia, University of Texas Health Science Center, Houston, reporting that elevated adenosine levels may lead to increased IL-6 activity via ADORA2B regulation in a mouse model of sickle cell-associated pain. Seol Hee Im, MD Anderson, Houston, wrapped up the session with a discussion of a model for detecting thermal thresholds in Drosophila by applying a heat probe to UV-damaged larvae and measuring rolling behavior. She reported that UV damage increased nociceptor firing rates and required the substance P receptor as evidenced in knockouts.
The meeting continued with updates on research in Texas covering mechanisms of CIPN as well as nerve injury. Karen Krukowski, MD Anderson, Houston, noted the high prevalence of nerve damage in chemotherapy patients and presented evidence that PFTμ prevents paclitaxel-induced mitochondrial damage in neurons and that metformin protects against intra-epidermal nerve fiber loss in animal models of CIPN, but neither is able to reverse established CIPN. However, the HDAC inhibitor ACY-1083 also appears to reduce CIPN, reverse glial cell activation, and may be an effective therapy against neuropathy and even numbness because it not only prevents CIPN but also reverses it. Cobi Heijnen, MD Anderson, Houston, noted the importance of the role of T cells and monocytes in the recovery from CIPN. She showed that T cell-deficient mice have a normal induction of CIPN pain but fail to recover from decreased mechanical thresholds. Moreover, her data indicated that CD8 cell treatment could induce recovery, potentially through production of IL-10 by monocytes. Michael Galko, MD Anderson, Houston, followed up with a presentation on the use of Drosophila to screen for genes expressed in larvae that do not develop UV-evoked thermal hypersensitivity. He reported that overexpressing the substance P receptor, TNF, or Hedgehog sensitizes normal larvae. He also discussed his work on a CIPN fruit fly model of sensitivity and peripheral neurodegeneration with the aim of genetically differentiating acute versus chronic responses. Carmen Dessauer, University of Texas Health Sciences Center, Houston, ended the session with a discussion of findings on the role of scaffolding proteins in persistent nociceptor sensitization via cAMP/PKA signaling in spinal cord-injured rodents.
Following a lunch break, Nathan Jeske, University of Texas Health Science Center, San Antonio, chaired a session on signaling mechanisms underlying pain chronification. He presented his latest findings on blocking hyperalgesia priming with mGluR antagonism and the role of the AKAP scaffolding protein. Li-Yen Mae Huang, University of Texas Medical Branch, Galveston, discussed findings from her lab uncovering details on communication between DRG soma and satellite cells. She presented findings that the soma releases ATP to satellite cells and that this communication depends on P2X7Rs. Shao-Jun Tang, University of Texas Medical Branch, Galveston, talked about the role of neuronal WNT signaling and astrocyte activation in pain associated with HIV in an animal model and by analysis of postmortem human tissues. Mario Romero-Ortega, UTD, wrapped up the session with a discussion of how electromagnetic signals can exacerbate pain associated with neuroma following amputation. His lab has developed a rodent model of neuroma, which displays nocifensive behaviors and allodynia when electromagnetic signals are applied to the neuroma.
The meeting moved on to a discussion of new findings in Texas in the field of trigeminal pain in a session chaired by Greg Dussor, UTD. He highlighted migraine as a pain disorder prevalent in the population needing a greater understanding of underlying pain mechanisms. He discussed his lab’s migraine model using dura cannulation to apply low pH to evoke facial (and hindpaw) mechanical allodynia, which can be reversed by blocking ASICs, and presented recent data indicating involvement of ASICs on dural fibroblasts for migraine. Phillip Kramer, Texas A&M University Baylor College of Dentistry, Dallas, presented a novel rat model of shingles facial pain. Injection of cells infected with the herpes zoster virus evoked facial mechanical and thermal sensitivity. He also reported that females appear to display greater sensitivity, similar to clinical reports on post-herpetic neuralgia. Another novel pain model was reported by Shivani Ruparel, University of Texas Health Science Center, San Antonio. She noted the high prevalence of head and neck cancer, highlighting the importance of gaining insight into the mechanisms underlying oral cancer pain. She reported that injection of human oral squamous cell carcinoma cells into a mouse tongue produces a localized tumor that induces ongoing pain as well as function-related mechanical sensitivity, both reversed by analgesics. Dayna Loyd Averitt, Texas Woman’s University, Denton, discussed the role of gonadal hormones in modulating trigeminal pain mechanisms. She reported recent findings indicating that peripheral serotonin can evoke pain via activating TRPV1-expressing trigeminal nociceptors, and that serotonin-evoked thermal hypersensitivity is influenced by gonadal hormones in both female humans and rodents.
Invited speaker, Rob Gereau, Washington University, St Louis, US, gave a keynote presentation highlighting the importance of not only peripheral, but also central, sensitization in various pain patients, specifically noting migraineurs. He noted the spinal involvement of mGluRs, particularly the Gq-coupled mGluR1 and mGluR5, and ERK signaling in central sensitization. He presented data showing the efficacy of mGluR5 antagonism, with a focus on Fenobam, to decrease pain sensitivity across somatic, visceral, and neuropathic pain models, with no adverse effects on motor coordination. He went on to describe his lab’s recent work utilizing capsaicin injection in healthy volunteers to test Fenobam’s efficacy against secondary hyperalgesia as a measure of central sensitization. This enlightening day ended with dinner and a poster session comprising presentations from 34 postdoctoral fellows, and graduate and undergraduate students representing pain research labs across Texas. This session provided ample opportunity to interact with all the attending members of the consortium and was a perfect way to catch up with friends and colleagues.
Bryan Black of UT Dallas at poster session.
The second day of the conference started off with the formal announcement of the formation of the Texas Pain Research Consortium, spearheaded by Ted Price, Ken Hargreaves, Pat Dougherty, and Greg Dussor. This statewide consortium aims to strengthen and unify the expanding pain research efforts ongoing across the state. A discussion included determining the membership, collaborative projects, and goals of the consortium. Following the business meeting, newly appointed chair of the consortium, Jin Mo Chung, University of Texas Medical Branch, chaired a session on centrally mediated synaptic plasticity and pain. He emphasized the role of LTP and LTD in spinal circuits underlying central sensitization. He reported recent findings from his lab that spinothalamic tract neurons display LTP, and GABAergic interneurons display LTD, independent of whether the neuronal input is high or low, and speculated that the loss of GABA inhibition in the spinal cord may be due to additive effects of LTP and GABAergic LTD on sensitization. Ted Price, UTD, added that synaptic adhesion molecules, like neuroligins, play a role in GABAergic plasticity and discussed the potential for reversal of plasticity with neuroligin-2-disrupting peptides. He reported on research from his lab that GABAA agonists and antagonists display inverse effects in naive versus animals with a previous injury, and that spinal neuroligin-2 may underlie spinal GABA neuron plasticity. Feng Tao, Texas A&M University Baylor College of Dentistry, Dallas, discussed the effect of alcohol in the transition from acute to chronic pain. His recent research indicates that mice subjected to chronic exposure to ethanol display longer-lasting mechanical sensitivity following a plantar incision than unexposed mice and provided evidence of a potential role of glia activation and TNFα in the spinal cord for producing this effect. Perry Fuchs, University of Texas at Arlington, concluded the session with a presentation of his lab’s approach to examining the biopsychosocial factors underlying chronic pain in animals. He stressed the need to consider the motivational and affective components of pain along with the sensory component and presented the place escape/avoidance paradigm developed in his lab. He reported recent findings on the role of the anterior cingulate cortex in pain affect and pain-enhanced frustration-type behaviors utilizing this paradigm.
The symposia concluded with a session on chronic pain and comorbidities. Geoffroy Laumet, MD Anderson, Houston, led the session underlining depression as a comorbidity and asking whether depression shares a common neuronal pathway with pain. He shared his findings that IDO1 is required for depressive behaviors in rodents, as measured by FST-induced immobility and reduced social exploration, but is not required for neuropathic mechanical sensitivity. Stacey Gorniak, University of Houston, discussed the contribution of tactile dysfunction to manual disability in type 2 diabetes patients. Using medial nerve blocks to mimic diabetic neuropathic numbness, her lab suggests that temporary tactile removal accounts for performance changes and sensory dysfunction involving both the central nervous system and the peripheral nervous system. Marina Asiedu, a postdoctoral fellow at UTD, discussed recent findings on the novel and highly efficacious AMPK inhibitor A769662, and offered evidence for a direct effect on voltage-gated Na+ channels. She postulates that this direct effect on reduction of current amplitude and a shift in current inactivation underlies the drug’s enhanced efficacy versus other AMPK activators, providing a new opportunity for drug development. Ending the session, and the meeting, Pooja Singhmar, MD Anderson, Houston, discussed the effects of GRK2 overexpression on Epac1 and Rap1 signaling. She reported that GRK2 inhibits Epac-Rap1 signaling by phosphorylation of Epac1 and inhibition of Epac reverses mechanical allodynia in models of inflammatory and neuropathic pain.
The meeting was adjourned by thanking Ted Price and Greg Dussor for their efforts in putting the meeting together and forming the Texas Pain Research Consortium. Overall, it was a very well-organized meeting that provided the opportunity to share research and meet and interact with other pain scientists in Texas with the goal of developing further collaboration. For this, we are very grateful to Patti Hurn, vice chancellor for Research and Innovation for the University of Texas System. Hopefully this was the first of many great Texas Pain Research Consortium meetings to come. Look for the 2016 meeting, which will tentatively be held in Austin, Texas.
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Image credit: UT Dallas
