Alexander R. Mikesell

ORCID: 0000-0002-8330-6608
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About
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Research Areas
  • Erythrocyte Function and Pathophysiology
  • Pain Mechanisms and Treatments
  • Cellular Mechanics and Interactions
  • Ion channel regulation and function
  • Blood properties and coagulation
  • Ion Channels and Receptors
  • Hereditary Neurological Disorders
  • Botulinum Toxin and Related Neurological Disorders
  • Stress Responses and Cortisol
  • Tendon Structure and Treatment
  • Neuropeptides and Animal Physiology
  • Veterinary Pharmacology and Anesthesia
  • Neurobiology and Insect Physiology Research
  • Chemical and Physical Studies
  • Advancements in Transdermal Drug Delivery
  • Bee Products Chemical Analysis
  • Cancer Treatment and Pharmacology
  • Lipid Membrane Structure and Behavior
  • Biofield Effects and Biophysics
  • Planarian Biology and Electrostimulation

Medical College of Wisconsin
2020-2025

Tactile and spontaneous pains are poorly managed symptoms of inflammatory neuropathic injury. Here, we found that transient receptor potential canonical 5 (TRPC5) is a chief contributor to both these sensations in multiple rodent pain models. Use TRPC5 knockout mice inhibitors revealed selectively contributes the mechanical hypersensitivity associated with CFA injection, skin incision, chemotherapy induced peripheral neuropathy, sickle cell disease, migraine, all which were characterized by...

10.1126/scitranslmed.abd7702 article EN Science Translational Medicine 2021-05-26

Epidermal keratinocytes mediate touch sensation by detecting and encoding tactile information to sensory neurons. However, the specific mechanotransducers that enable respond mechanical stimulation are unknown. Here, we found mechanically-gated ion channel PIEZO1 is a key keratinocyte mechanotransducer. Keratinocyte expression of critical for normal afferent firing behavioral responses stimuli in mice.

10.7554/elife.65987 article EN cc-by eLife 2022-09-02

The present study was designed to investigate the role of Schwann cell (SC) Piezo1 in peripheral nociception. We first developed an AAV vector that has primary SC tropism after delivery into sciatic (or tibial) nerve. This achieved by packing AAV-GFP transcribed a CBA promoter using capsid AAVolig001 generate AAVolig001-CBA-GFP. Six weeks intraneural injection AAVolig001-CBA-GFP naive rats, GFP expression detected selectively both myelinating SCs (mSCs) and non-myelinating (nmSCs). A dual...

10.1016/j.omtm.2025.101433 article EN cc-by-nc-nd Molecular Therapy — Methods & Clinical Development 2025-02-12

Few analgesics identified using preclinical models have successfully translated to clinical use. These translational limitations may be due the unidimensional nature of behavioral response measures used assess rodent nociception. Advances in high-speed videography for pain behavior allow objective quantification nuanced aspects evoked paw withdrawal responses. However, whether videography-based assessments mechanical hypersensitivity outperform traditional measurement reproducibility is...

10.1097/j.pain.0000000000003174 article EN Pain 2024-02-02

Abstract Epidermal keratinocytes mediate touch sensation by detecting and encoding tactile information to sensory neurons. However, the specific mechanotransducers that enable respond mechanical stimulation are unknown. Here, we found mechanically-gated ion channel Piezo1 is major keratinocyte mechanotransducer. Keratinocyte expression of critical for normal afferent firing behavioral responses stimuli.

10.1101/2020.07.19.211086 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-07-19

Recent work demonstrates that epidermal keratinocytes are critical for normal touch sensation. However, it is unknown whether contribute to touch-evoked pain and hypersensitivity after tissue injury. Here, we used a mouse model of paclitaxel treatment determine the extent which keratinocyte activity contributes severe neuropathic accompanies chemotherapy. We found inhibition by either optogenetic or chemogenetic methods largely alleviated paclitaxel-induced mechanical across acute persistent...

10.1126/scitranslmed.adn5629 article EN Science Translational Medicine 2024-12-11

Abstract Recent work demonstrates that epidermal keratinocytes are critical for normal touch sensation. However, it is unknown if contribute to evoked pain and hypersensitivity following tissue injury. Here, we used inhibitory optogenetic chemogenetic techniques determine the extent which keratinocyte activity contributes severe neuropathic accompanies chemotherapeutic treatment. We found inhibition largely alleviates paclitaxel-induced mechanical hypersensitivity. Furthermore, paclitaxel...

10.1101/2023.12.12.571332 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2023-12-13

Abstract We previously reported functional Piezo1 expression in Schwann cells of the peripheral nervous system. This study is designed to further investigate role cell nociception. first developed an adeno-associated viral (AAV) vector that has primary tropism after delivery into sciatic nerve. was achieved by packing AAV-GFP transcribed a hybrid CMV enhancer/chicken β-actin (CBA) promoter using capsid AAVolig001 generate AAVolig001-CBA-GFP. Five weeks intrasciatic injection...

10.21203/rs.3.rs-3405016/v1 preprint EN cc-by Research Square (Research Square) 2023-10-16

Abstract Persistent tactile pain is a poorly managed symptom of inflammatory and neuropathic injury. To develop therapies for this maladaptive sensation, the underlying molecular mediators must be identified. Using knockout mice pharmacological inhibitors, we identified transient receptor canonical 5 (TRPC5) as key contributor to persistent that occurs in many preclinical rodent models. TRPC5 inhibition was effective injuries associated with elevated levels bioactive phospholipid...

10.1101/2020.07.13.201186 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2020-07-14
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