Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell anemia is a common genetic disorder in African Americans. Opioid analgesics are traditionally the treatment for the severe pain associated with this disease. Here we reveal that the opioid antagonist naloxone possesses potent analgesic activity in two transgenic mouse models of sickle cell anemia (NY1DD and hBERK1) and not in their respective controls (ICR-CD1 and C57BL/6J) when administered by three parenteral routes [intracerebroventricular (i.c.v.), intrathecal, and subcutaneous]. In the NY1DD mice, naloxone (i.c.v.) possessed approximately 300-fold greater potency than morphine (i.c.v.). Other opioid antagonists (naltrexone, norbinaltorphimine, and naltrindole) were substantially less effective in producing analgesia. Naloxone and morphine were synergistic in NY1DD mice, suggesting different receptor systems. Microarray analysis suggested naloxone-induced down-regulation of the CC chemokine receptor (CCR)5 in NY1DD mice but not in control mice. Pretreatment of control mice with CC chemokine ligand 5 [CCL5 (RANTES)] enabled naloxone to produce analgesia similar to that observed in NY1DD mice. Mu opioid receptor knockout mice treated similarly also displayed analgesia. That the effect of CCL5 was specifically related to CCR5 and/or CCR1 activation was demonstrated by antagonism of analgesia with the chemokine antagonist methionylated RANTES. Similar antagonism of naloxone-induced analgesia also was observed when NY1DD mice were pretreated with methionylated RANTES. These results indicate that CCR5/CCR1 receptors are directly or indirectly involved in analgesia produced by naloxone. The present study suggests that naloxone may be clinically useful in the treatment of pain associated with sickle cell disease and other disorders involving inflammation.
 ...
PMID:Naloxone acts as a potent analgesic in transgenic mouse models of sickle cell anemia. 1738 63

Neuropathic pain is a chronic condition which significantly reduces the quality of life and serious clinical issue that is in general resistant to available therapies. Therefore looking for new analgesics is still critical issue. Recent, studies have indicated that chemokine signaling pathways are crucial for the development of neuropathy; however, the role of CC chemokine receptor 4 (CCR4) in this process has not yet been studied. Therefore, the aim of our research was to investigate the influence of C021 (a CCR4 antagonist) and CCR4 CC chemokine ligands 17 and 22 (CCL17 and CCL22) on the development of hypersensitivity and the effectiveness of morphine induced analgesia in naive animals and/or animals exposed to chronic constriction injury (CCI) of the sciatic nerve. Firstly, we demonstrated that the intrathecal administration of CCL17 and CCL22 induced pain-related behavior in naive mice. Secondly, we revealed that the intrathecal injection of C021 significantly reduced CCI-induced hypersensitivity after nerve injury. In parallel, C021 reduced microglia/macrophages activation and the level of some pronociceptive interleukins (IL-1beta; IL-18) in the spinal cord 8 days after CCI. Moreover, C021 not only attenuated mechanical and thermal hypersensitivity but also enhanced the analgesic properties of morphine. Our research indicates that CCR4 ligands might be important factors in the early stages of neuropathy, when we observe intense microglia/macrophages activation. Moreover, pharmacological blockade of CCR4 may serve as a potential new target for better understanding the mechanisms of neuropathic pain development.
 ...
PMID:CCR4 antagonist (C021) influences the level of nociceptive factors and enhances the analgesic potency of morphine in a rat model of neuropathic pain. 3240 23