Abstract: This invention is in the field of medicinal pharmacology. In particular, the invention relates to a new class of small-molecules having a pyrazino-pyrimidine-dione (or related) structure which function as modulators (activators, inhibitors) of protease activated receptor type 2 (PAR2), and their use as therapeutics for the treatment of conditions involving PAR2 activity (e.g., asthma, chronic pain, cancer and/or vascular disorders).

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) is a primary dose-limiting side effect caused by antineoplastic agents, such as paclitaxel. This causes damage to peripheral nerves and the dorsal root ganglia (DRG). Currently, there are no effective treatments for CIPN, which can lead to long-term morbidity in patients and survivors. Neuronal-immune interactions occur in CIPN and have been implicated both in the development and progression of the disease and disease resolution. The inventors investigated the potential role of Inducible co-stimulatory molecule (ICOS) in the resolution of CIPN. ICOS is an immune checkpoint molecule that is expressed on the surface of activated T cells and promotes proliferation and differentiation of T cells. They found that intrathecal administration of ICOS agonist antibody (ICOSaa) alleviates mechanical hypersensitivity caused by paclitaxel and facilitates the resolution of pain in female mice without a clear benefit in male mice.

Abstract: Compounds having activity as inhibitors of MNK are provided. One embodiment provides compounds having Structure (II): Formula (II) or a pharmaceutically acceptable salt, stereoisomer, tautomer, or prodrug thereof, wherein R1a, R1b, R2, X, Y, and L are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of MNK are also provided.

Abstract: The disclosure provides methods and compositions for inhibiting pain and comorbid cognitive deficits by administering a MNK inhibitor to a subject in need thereof. Also provided are methods of using the inhibitor in combination with other pain therapies.

Abstract: The present disclosure describes chemically-stabilized RNA substrates that hybridize to poly-A binding protein (PABP) with high specificity in vitro, as well as their use in impairs nascent translation in a PABP-dependent mechanism in cells, thereby treating pain.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the invention relates to protease activated receptor type 2 (PAR2) modulating compounds (e.g., mimetic peptides), compositions comprising such modulating compounds, and their use as therapeutics for the treatment of conditions involving PAR2 activity.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the invention relates to protease activated receptor type 3 (PAR3) modulating compounds (e.g., mimetic peptides), compositions comprising such modulating compounds, and their use as therapeutics for the treatment of conditions involving PAR3 activity.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the invention relates to a new class of small-molecules having a pyrazino-pyrimidine-dione (or related) structure which function as modulators (activators, inhibitors) of protease activated receptor type 2 (PAR2), and their use as therapeutics for the treatment of conditions involving PAR2 activity (e.g., asthma, chronic pain, cancer and/or vascular disorders).

Abstract: The present disclosure provides ophthalmic compositions containing resveratrol. Also provided are methods of using ophthalmic resveratrol compositions to treat acute ocular pain, chronic ocular pain, dry eye disease, and/or photophobia.

Abstract: The present disclosure describes chemically-stabilized RNA substrates that hybridize to poly-A binding protein (PABP) with high specificity in vitro, as well as their use in impairs nascent translation in a PABP-dependent mechanism in cells, thereby treating pain.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the invention relates to protease activated receptor type 2 (PAR2) modulating compounds (e.g., mimetic peptides), compositions comprising such modulating compounds, and their use as therapeutics for the treatment of conditions involving PAR2 activity.

Abstract: This invention is in the field of medicinal pharmacology. In particular, the invention relates to protease activated receptor type 3 (PAR3) modulating compounds (e.g., mimetic peptides), compositions comprising such modulating compounds, and their use as therapeutics for the treatment of conditions involving PAR3 activity.

Abstract: Methods and compositions using a combination of adenosine monophosphate protein kinase (AMPK) activators for treating pain such as post-surgical pain or development of chronic pain. The two or more AMPK activators work synergistically and may be administered in individually sub-efficacious doses. The AMPK activators may have different mechanisms of AMPK activation. The AMPK activators may be administered systemically and/or topically in, for example, as a gel, ointment, cream, lotion, suspension, liquid, or transdermal patch.

Abstract: Methods and compositions using a combination of adenosine monophosphate protein kinase (AMPK) activators for treating pain such as post-surgical pain or development of chronic pain. The two or more AMPK activators work synergistically and may be administered in individually sub-efficacious doses. The AMPK activators may have different mechanisms of AMPK activation. The AMPK activators may be administered systemically and/or topically in, for example, as a gel, ointment, cream, lotion, suspension, liquid, or transdermal patch.

Abstract: A topical composition containing an adenosine monophosphate protein kinase (AMPK) activator and methods of administering the AMPK activator for treating acute pain or preventing the development of chronic pain in a subject. The AMPK activator is resveratrol. A second AMPK activator may also be used. The second AMPK activator is metformin. The topical composition may be administered as a gel, ointment, cream, lotion, suspension, liquid, or transdermal patch.