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WELCOME TO THE
MICKLE LAB

Visceral Pain and Neurophysiology Lab

Our lab research goals are to study and develop tools to better understand the multifaceted nature of visceral pain conditions and related pathophysiology. Like most chronic pain conditions visceral pain conditions likely involve multiple mechanistic changes throughout the body. Our lab aims to study the diverse mechanistic signaling and interactions of these diseases using multiple advanced technological approaches including, biochemical, live-cell imaging, electrophysiology and optogenetic techniques. Further we actively collaborate with engineers from different fields to develop new and innovative technologies that can assist us in better understanding and treating chronic pain.

 

RESEARCH

Development of technology to study visceral diseases and refine current/develop new analgesic technologies

Our lab works closely with material, chemical and electrical engineers to develop new tools to study the nervous system with the end goal using these tools to study the changes that occur in these systems during and after the development of chronic pain, as well as the hopeful end goal of implementing these strategies in patients.

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The role of immune cell signaling in interstitial cystitis/ bladder pain syndrome (IC/BPS) pain

IC/BPS is idiopathic in nature, however over the past two decades mounting evidence suggests alterations to the innate immune response may play a role in the symptomology and progression of the disease. Our lab aims to study the involvement of different immune cells in pain and bladder dysfunction associated with models of IC/BPS

Urothelial cell-to-sensory afferent signaling in bladder pain and function

Urothelial cells, the endothelial cells that line the bladder wall, were classically thought to function as a passive barrier. However, evidence collected over the last decade has shown them to be a much more active component of bladder physiology and pathophysiology. The fact that urothelial cells express many different types of sensory receptors, ion channels, signaling peptides and neurotransmitters, along with their close proximity to nerve fibers suggest that they could communicate and/or receive input from neuronal cells. Our lab is using innovative techniques to isolate these signaling mechanisms to specific cell types with the goal of understanding how these cells communicate under normal physiologic conditions as well as how the signaling may be altered under disease conditions.

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AVAILABLE POSITIONS

Research Opportunities

August 5th 2019

ACTIVELY RECRUITING HIGHLY MOTIVATED POST-DOCS, LAB TECHNICIANS, AND GRADUATE STUDENTS

Please contact email me at  - amickle at ufl.edu

September 19th 2019

POSTDOCTORAL RESEARCHER

The Mickle Lab is looking for a highly-motivated post-doctoral researcher to join our group studying mechanisms of visceral pain and disease. The postdoctoral researcher would have the opportunity to lead studies involving signaling between nociceptors and non-neuronal cells in models of interstitial cystitis and bladder pain, as well as work closely with mechanical, electrical and biological engineers to develop tools to study and eventually treat visceral pain disorders.

The postdoctoral researcher will have the potential to learn primary neuronal culture, electrophysiology, calcium imaging, optogenetic and animal behavioral assays. Additionally, the candidate will receive guidance on career goals, scientific communication, and student mentorship/supervision. There will be opportunities and expectations to present their work at local and national meetings.

The lab is located at the University of Florida in Gainesville Florida, which is ~2 hours from Orlando, Jacksonville and Tampa Bay. The UF is the largest and oldest university in the state and is the 6th largest university campus by enrollment in the USA. The university has a thriving research community spanning 16 different colleges. The office of Postdoctoral Affairs (http://postdoc.aa.ufl.edu/) at UF serves the post-doctoral community by orienting and connecting postdocs to resources to support their professional development and wellbeing.

Applicants should have recently obtained (or be about to receive) a Ph.D. in neuroscience, physiology, biology or equivalent. Experience with cell culture, mouse handling and small animal surgery is desired but not required. Candidates should be self-motivated, and have excellent communication skills. We highly value hard work, curiosity, innovation, teamwork and professional development, in combination with a healthy work/life balance.

Questions about the position can be directed to amickle at ufl.edu.

To apply submit a cover letter and CV with 3 references to (amickle at ufl.edu ).

 

PUBLISHED WORK

 

July 5, 2019

Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies.

02 January 2019

Nature 565, pages361–365 (2019)

The fast-growing field of bioelectronic medicine aims to develop engineered systems that can relieve clinical conditions by stimulating the peripheral nervous system. This type of technology relies largely on electrical stimulation to provide neuromodulation of organ function or pain. One example is sacral nerve stimulation to treat overactive bladder, urinary incontinence and interstitial cystitis (also known as bladder pain syndrome). Conventional, continuous stimulation protocols, however, can cause discomfort and pain, particularly when treating symptoms that can be intermittent (for example, sudden urinary urgency). Direct physical coupling of electrodes to the nerve can lead to injury and inflammation. Furthermore, typical therapeutic stimulators target large nerve bundles that innervate multiple structures, resulting in a lack of organ specificity. Here we introduce a miniaturized bio-optoelectronic implant that avoids these limitations by using (1) an optical stimulation interface that exploits microscale inorganic light-emitting diodes to activate opsins; (2) a soft, high-precision biophysical sensor system that allows continuous measurements of organ function; and (3) a control module and data analytics approach that enables coordinated, closed-loop operation of the system to eliminate pathological behaviours as they occur in real-time. In the example reported here, a soft strain gauge yields real-time information on bladder function in a rat model. Data algorithms identify pathological behaviour, and automated, closed-loop optogenetic neuromodulation of bladder sensory afferents normalizes bladder function. This all-optical scheme for neuromodulation offers chronic stability and the potential to stimulate specific cell types.

Pain. 2018 Sep;159 Suppl 1:S65-S73

Optogenetics is a powerful technique that has transformed the field of neuroscience by allowing unprecedented temporal and spatial control of neuronal activity. This technology has enabled major advancements in mapping complex neuronal circuits and in understanding the functional significance of individual cell types within these circuits. Optogenetic approaches have been broadly applied to studies of the brain, but implementation of these techniques in the spinal cord and peripheral nervous system, as well as in other peripheral tissues has developed more slowly due to challenges in light delivery to these structures. Here, we review strategies for opsin expression in peripheral tissues, as well as recent advances in implantable, wireless light sources that have opened the door to a variety of studies applying optogenetics outside the brain, including recent advances relevant to the study of pain.

Proceedings of National Academy of Sciences. 2018 Aug 21;115(34):E8057-E8066

Peripheral nerve damage initiates a complex series of structural and cellular processes that culminate in chronic neuropathic pain. The recent success of a type 2 angiotensin II (Ang II) receptor (AT2R) antagonist in a phase II clinical trial for the treatment of postherpetic neuralgia suggests angiotensin signaling is involved in neuropathic pain. However, transcriptome analysis indicates a lack of AT2R gene (Agtr2) expression in human and rodent sensory ganglia, raising questions regarding the tissue/cell target underlying the analgesic effect of AT2R antagonism. We show that selective antagonism of AT2R attenuates neuropathic but not inflammatory mechanical and cold pain hypersensitivity behaviors in mice. Agtr2-expressing macrophages (MΦs) constitute the predominant immune cells that infiltrate the site of nerve injury. Interestingly, neuropathic mechanical and cold pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral MΦs and AT2R-null hematopoietic cell transplantation. Our study identifies AT2R on peripheral MΦs as a critical trigger for pain sensitization at the site of nerve injury, and therefore proposes a translatable peripheral mechanism underlying chronic neuropathic pain.

  • Won SM*, Koo J*, Crawford KE*, Mickle AD,  Xue Y, Min S, McIlvried LA, Yan Y, Kim SB, Lee SM, MacEwan MR, Huang Y, Gereau RW, Rogers JA. Natural Wax for Transient Electronics. Advanced Functional Materials. 2018. doi: 10.1002/adfm.201801819.

  • Shepherd AJ, Copits BA*, Mickle AD*, Karlsson P*, Kadunganattil S*, Haroutounian S, Tadinada SM, de Kloet AD, Valtcheva MV, McIlvried LA, Sheahan TD, Jain S, Ray PR, Usachev YM,  Dussor G, Krause EG, Price TJ, Gereau RW, Mohapatra DP. Angiotensin II triggers painful macrophage-to-sensory neuron redox crosstalk. Journal of Neuroscience. 2018 Aug 8;38(32):7032-7057. doi: 10.1523/JNEUROSCI.3542-17.2018. PubMed PMID: 2997662

  • Shepherd AJ, Mickle AD, McIlvried LA, Gereau RW, Mohapatra DP. Parathyroid Hormone-related Peptide Activates and Modulates TRPV1 Channel in Human DRG Neurons. European Journal of Pain. 2018 doi: 10.1002/ejp.1251. PubMed PMID:29797679.


  • Shepherd AJ*, Mickle AD*, Kadunganattil S*, Hu H, Mohapatra DP. Parathyroid Hormone-related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity. Frontiers in Cellular Neuroscience. 2018. Frontiers in Cellular Neuroscience. doi: 10.3389/fncel.2018.00038. PubMed PMID:29497363 


  • Noh KN, Park SI, Qazi R, Zou Z, Mickle AD, Grajales-Reyes JG, Jang KI, Gereau RW, Xiao J, Rogers JA, Jeong JW. Miniaturized, Battery-Free Optofluidic Systems with Potential for Wireless Pharmacology and Optogenetics. Small. 2018. doi: 10.1002/smll.201702479. PubMed PMID: 29215787.


  • Samineni VK*, Mickle AD*, Yoon J, Grajales-Reyes JG, Pullen MY, Crawford KE, Noh KN, Gereau GB, Vogt SK, Lai HH, Rogers JA, Gereau RW. Optogenetic silencing of nociceptive primary afferents reduces evoked and ongoing bladder pain. Scientific Reports. 2017;7(1):15865. doi: 10.1038/s41598-017-16129-3. PubMed PMID: 29158567


  • Samineni VK, Yoon J, Crawford KE, Jeong YR, McKenzie KC, Shin G, Xie Z, Sundaram SS, Li Y, Yang MY, Kim J, Wu D, Xue Y, Feng X, Huang Y, Mickle AD, Banks A, Ha JS, Golden JP, Rogers JA, Gereau RWt. Fully implantable, battery-free wireless optoelectronic devices for spinal optogenetics. Pain. 2017. doi: 10.1097/j.pain.0000000000000968. PubMed PMID: 28700536.


  • Shin G, Gomez AM, Al-Hasani R, Jeong YR, Kim J, Xie Z, Banks A, Lee SM, Han SY, Yoo CJ, Lee JL, Lee SH, Kurniawan J, Tureb J, Guo Z, Yoon J, Park SI, Bang SY, Nam Y, Walicki MC, Samineni VK, Mickle AD, Lee K, Heo SY, McCall JG, Pan T, Wang L, Feng X, Kim TI, Kim JK, Li Y, Huang Y, Gereau RWt, Ha JS, Bruchas MR, Rogers JA. Flexible Near-Field Wireless Optoelectronics as Subdermal Implants for Broad Applications in Optogenetics. Neuron. 2017;93(3):509-21 e3. doi: 10.1016/j.neuron.2016.12.031. PubMed PMID: 28132830.


  • Mickle AD, Shepherd AJ, Mohapatra DP. Nociceptive Trp Channels: Sensory Detectors and Transducers in Multiple Pain Pathologies. Pharmaceuticals. 2016;9(4). doi: 10.3390/ph9040072. PubMed PMID: 27854251.

Contact us for more information about our research and publications.

LAB MEMBERS

Principle Investigator

I am a Ph.D. neuroscientist with a diverse research background that includes: behavioral neuroscience, molecular and cellular neuroscience, neuropharmacology, neurophysiology, urology, and bioengineering. My current research is focused on incorporating molecular, cellular, and whole-animal approaches to answer questions in relation to mechanisms of pain and pain relief. I have extensive interest in continuing to advance the field of pain research, education, and training.

 

CONTACT US

Thanks for your interest in our research. Email amickle at ufl . edu.

University of Florida
College of Veterinary Medicine
Basic Science Building - B3-15
1333 Center Dr, Gainesville, FL 32610

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