Pain
-
Joint pain is a common clinical problem for which both inflammatory and degenerative joint diseases are major causes. The purpose of this study was to investigate the role of CB1 and CB2 cannabinoid receptors in the behavioral, histological, and neurochemical alterations associated with joint pain. The murine model of monosodium iodoacetate (MIA) was used to induce joint pain in knockout mice for CB1 (CB1KO) and CB2 cannabinoid receptors (CB2KO) and transgenic mice overexpressing CB2 receptors (CB2xP). ⋯ All mouse lines developed similar histological changes after MIA intra-articular injection. Nevertheless, MIA intra-articular injection produced specific changes in the expression of cannabinoid and opioid receptor genes in lumbar spinal cord sections that were further modulated by the genetic alteration of the cannabinoid receptor system. These results revealed that CB2 receptor plays a predominant role in the control of joint pain manifestations and is involved in the adaptive changes induced in the opioid system under this pain state.
-
The influence of pain descriptors and mechanical hypersensitivity on pain severity in neuropathic pain has not been well researched and is poorly understood. The aim of this study was to determine the relationship between pain severity and other factors describing chronic neuropathic pain in a large cohort of patients with self-reported neuropathic pain potentially recruited as subjects for a Phase IIa study. A questionnaire specific to the study parameters covering demographics and pain characteristics was sent to potential participants. ⋯ Having 3 or 4 pain descriptors was also strongly indicative of both moderate and severe pain. Female gender, age, and history of serious mental disorders were found to be weaker indicators of both moderate and severe pain. Given the large and varied population with many neuropathic pain diagnoses in the study, the findings are not likely to be merely chance, but are likely to reflect important relationships between pain severity and other factors in those who suffer from chronic neuropathic pain.
-
Environmentally caused changes in chromosomes that do not alter the DNA sequence but cause phenotypic changes by altering gene transcription are summarized as epigenetics. A major epigenetic mechanism is methylation or demethylation at CpG-rich DNA islands. DNA methylation triggered by drugs has largely unexplored therapeutic consequences. ⋯ This has phenotypic consequences for pain and may provide a new, epigenetics-associated mechanism of opioid-induced hyperalgesia. The results indicate a potential influence of opioid analgesics on the patients' epigenome. They emphasize the need for reliable and cost-effective screening tools and may imply that high-throughput screening for lead compounds in artificial expression systems may not provide the best tools for identifying new pain medications.