Identification and characterization of novel candidate compounds targeting 6- and 7-transmembrane μ-opioid receptor isoforms.

Background And Purpose: The μ-opioid receptor (μ receptor) is the primary target for opioid analgesics. The 7-transmembrane (TM) and 6TM μ receptor isoforms mediate inhibitory and excitatory cellular effects. Here, we developed compounds selective for 6TM- or 7TM-μ receptors to further our understanding of the pharmacodynamic properties of μ receptors.

A functional substitution in the L-aromatic amino acid decarboxylase enzyme worsens somatic symptoms via a serotonergic pathway.

Objective: Heightened somatic symptoms are reported by a wide range of patients with chronic pain and have been associated with emotional distress and physical dysfunction. Despite their clinical significance, molecular mechanisms leading to their manifestation are not understood.

Methods: We used an association study design based on a curated list of 3,295 single nucleotide polymorphisms mapped to 358 genes to test somatic symptoms reporting using the Pennebaker Inventory of Limbic Languidness questionnaire from a case-control cohort of orofacial pain (n = 1,607).

Genetic pathway analysis reveals a major role for extracellular matrix organization in inflammatory and neuropathic pain.

Chronic pain is a debilitating and poorly treated condition whose underlying mechanisms are poorly understood. Nerve injury and inflammation cause alterations in gene expression in tissues associated with pain processing, supporting molecular and cellular mechanisms that maintain painful states. However, it is not known whether transcriptome changes can be used to reconstruct a molecular pathophysiology of pain.

Human pain genetics database: a resource dedicated to human pain genetics research.

The Human Pain Genetics Database (HPGDB) is a comprehensive variant-focused inventory of genetic contributors to human pain. After curation, the HPGDB currently includes 294 studies reporting associations between 434 distinct genetic variants and various pain phenotypes. Variants were then submitted to a comprehensive analysis.

Differences in the Antinociceptive Effects and Binding Properties of Propranolol and Bupranolol Enantiomers.

Unlabelled: Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective β-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and bupranolol for all 3 β-ARs.

COMT gene locus: new functional variants.

Catechol-O-methyltransferase (COMT) metabolizes catecholaminergic neurotransmitters. Numerous studies have linked COMT to pivotal brain functions such as mood, cognition, response to stress, and pain. Both nociception and risk of clinical pain have been associated with COMT genetic variants, and this association was shown to be mediated through adrenergic pathways.