Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

Purpose Of Review: Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges.

Discovery and evaluation of nNa1.5 sodium channel blockers with potent cell invasion inhibitory activity in breast cancer cells.

Voltage-gated sodium channels (VGSC) are a well-established drug target for anti-epileptic, anti-arrhythmic and pain medications due to their presence and the important roles that they play in excitable cells. Recently, their presence has been recognized in non-excitable cells such as cancer cells and their overexpression has been shown to be associated with metastatic behavior in a variety of human cancers. The neonatal isoform of the VGSC subtype, Na1.

Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.

This review focuses on our efforts to translate a low-toxicity retinoid X receptor-selective agonist, UAB30, to the clinic for the prevention of breast cancers. The review is divided into several sections. First, the current status of breast cancer prevention is discussed.

Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers.

(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid (UAB30) is currently undergoing clinical evaluation as a novel cancer prevention agent. In efforts to develop even more highly potent rexinoids that prevent breast cancer without toxicity, we further explore here the structure-activity relationship of two separate classes of rexinoids. UAB30 belongs to the class II rexinoids and possesses a 9Z-tetraenoic acid chain bonded to a tetralone ring, whereas the class I rexinoids contain the same 9Z-tetraenoic acid chain bonded to a disubstituted cyclohexenyl ring.

Methyl substitution of a rexinoid agonist improves potency and reveals site of lipid toxicity.

(2E,4E,6Z,8E)-8-(3',4'-Dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid, 9cUAB30, is a selective rexinoid that displays substantial chemopreventive capacity with little toxicity. 4-Methyl-UAB30, an analogue of 9cUAB30, is a potent RXR agonist but caused increased lipid biosynthesis unlike 9cUAB30. To evaluate how methyl substitution influenced potency and lipid biosynthesis, we synthesized four 9cUAB30 homologues with methyl substitutions at the 5-, 6-, 7-, or 8-position of the tetralone ring.