Papers by Tally Largent-Milnes
American Journal of Physiology-heart and Circulatory Physiology, Nov 1, 2022
Cerebral parenchymal arterioles from menopause mice showed increased myogenic tone. We identified... more Cerebral parenchymal arterioles from menopause mice showed increased myogenic tone. We identified an impairment in smooth muscle cell BKCa channel activity, without a reduction in endothelium-dependent dilation or nitric oxide production. Microvascular dysfunction was associated with a reduction in neurovascular responses after somatosensory stimulation. Despite the neurovascular impairment, cognitive abilities were maintained in menopausal mice.
International Journal of Molecular Sciences
Pain is the most significant impairment and debilitating challenge for patients with bone metasta... more Pain is the most significant impairment and debilitating challenge for patients with bone metastasis. Therefore, the primary objective of current therapy is to mitigate and prevent the persistence of pain. Thus, cancer-induced bone pain is described as a multifaceted form of discomfort encompassing both inflammatory and neuropathic elements. We have developed a novel non-addictive pain therapeutic, PNA6, that is a derivative of the peptide Angiotensin-(1-7) and binds the Mas receptor to decrease inflammation-related cancer pain. In the present study, we provide evidence that PNA6 attenuates inflammatory, chemotherapy-induced peripheral neuropathy (CIPN) and cancer pain confined to the long bones, exhibiting longer-lasting efficacious therapeutic effects. PNA6, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-Lact)-amide, was successfully synthesized using solid phase peptide synthesis (SPPS). PNA6 significantly reversed inflammatory pain induced by 2% carrageenan in mice. A second murine model of p...
Research Square (Research Square), Jun 11, 2021
Frontiers in Pharmacology, Apr 16, 2021
The Journal of Pain, Dec 1, 2021
Benefits of phototherapy were characterized in multiple diseases including depression, circadian ... more Benefits of phototherapy were characterized in multiple diseases including depression, circadian rhythm disruptions, and neurodegeneration. Studies on migraine and fibromyalgia patients revealed that green light-emitting diodes (GLED) exposure provides a pragmatic and safe therapy to manage chronic pain. In rodents, GLED reversed hypersensitivity related to neuropathic pain. However, little is known about the underlying mechanisms of GLED efficacy. Here, we sought to understand how green light modulates the endogenous opioid system. We first characterized how exposure to GLED stimulates release of β-endorphin and proenkephalin in the central nervous system of male rats. Moreover, by individually editing each of the receptors, we found that μ- and δ-opioid receptors are required for green light’s antinociceptive effect in naïve rats and a model of HIV-induced peripheral neuropathy. We investigated how GLED could increase pain thresholds, and explored its potential in reversing hypersensitivity in a model of HIV-related neuropathy. Through behavioral and gene editing approaches, we identified that green light provides antinociception via modulation of the endogenous opioid system in the spinal cord. This work identifies a previously unknown mechanism by which GLED can improve pain management. Clinical translation of these results will advance the development of an innovative therapy devoid of adverse effects.
Frontiers in Neuroscience, Apr 18, 2023
Neuroscience Letters, Oct 1, 2022
Proceedings of the National Academy of Sciences of the United States of America, May 8, 2019
ACS Chemical Neuroscience, Dec 6, 2022
Current Topics in Pharmacology, 2017
Springer eBooks, 2018
Chronic pain is a widespread problem that plagues an estimated 10 to 30% of the world’s populatio... more Chronic pain is a widespread problem that plagues an estimated 10 to 30% of the world’s population. The current therapeutic repertoire is inadequate in managing patient pain with narcotic use resulting in a drug overdose epidemic, affirming the need for the development of new therapeutics. Adenosine and its four cognate receptors (A1AR, A2AAR, A2BAR, and A3AR) play essential roles in physiological and pathophysiological states, including chronic pain. For decades, preclinical and clinical studies have revealed that adenosine and A1AR- and to a lesser extent A2AAR-selective agonists have analgesic properties, yet their therapeutic utility has been limited by adverse cardiovascular side effects. There is no evidence that A2BAR plays a role in pain. Recent preclinical studies have demonstrated that selective A3AR agonists result in antinociception in models of acute and chronic pain while lacking unwanted side effects. These exciting preclinical observations of A3AR agonists have been bolstered by clinical trials of A3AR agonists in other disease states including rheumatoid arthritis and psoriasis that suggests a clinical benefit without cardiotoxicity. Our goal herein is to briefly discuss adenosine and its receptors in the context of pathological pain and examine what is known at present regarding A3AR-mediated antinociception. We will highlight recent findings pertaining to A3AR in pain and describe possible pathways by which A3AR may mediate its effects and the current state of selective A3AR agonists used in pain studies. The adenosine-to-A3AR pathway represents an important endogenous system that can be targeted to provide safe, effective pain relief in patients suffering with chronic pain.
Pharmacology & Pharmacy, 2023
Journal of pharmaceutics & pharmacology, Dec 18, 2017
The Journal of Pain, Apr 1, 2015
Journal of Biosciences and Medicines, 2021
Journal of Pharmacology and Experimental Therapeutics, May 20, 2020
The FASEB Journal, Apr 1, 2015
Many cancerous solid tumors, including breast, metastasize to the bone and induce pain (CIBP). CI... more Many cancerous solid tumors, including breast, metastasize to the bone and induce pain (CIBP). CIBP is often severe due to an enhanced inflammation in the bone, rapid bone degradation, and nocicept...
Methods in molecular biology, 2019
Uploads
Papers by Tally Largent-Milnes