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

Nociceptive flexion reflexes, RIII reflex in particular, have been demonstrated to be a useful tool for pain research in humans, since the threshold of RIII reflex is that of pain. In this study a reduction of RIII reflex threshold, strictly related to the severity of the disease, is described in migraine with interval headache (MIH), that is considered a severe and evolutive form of common migraine (CM). These abnormalities were not found in CM or in other chronic pain conditions, i.e. chronic tensive headache (CTH), suggesting that this electrophysiological parameter may be useful in the clinical assessment of primary headache. Moreover, the administration of amitriptyline, a drug producing analgesia mainly by blocking serotonin uptake, was able to markedly increase the RIII reflex threshold in MIH. This fact supports the hypothesis that an impairment of serotoninergic antinociceptive system may exist in this type of headache. A significant correlation between percentage increase in RIII reflex threshold and reduction of PTI was also observed after amitriptyline treatment, indicating that pain reflex may be used for predicting treatment response in migraine.
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PMID:Pain reflexes in the clinical assessment of migraine syndromes. 360 72

Binding a critical pentapeptide region on the scaffolding protein filamin A regulates signaling of mu opioid receptors (MORs) so that their activation should not result in the opioid tolerance, dependence and addiction associated with current opioid painkillers. Additionally, we show that compounds that bind this site on filamin A reduce release of inflammatory cytokines. PTI-609 is a new chemical entity that binds filamin A with picomolar affinity and also activates opioid receptors via a novel binding domain. PTI-609 and analogs have similar analgesic efficacy to morphine by oral administration in mice, provide some anti-inflammatory activity in the rat collagen-induced arthritis model, and show no conditioned place preference at analgesic doses, suggesting no potential for abuse and addiction. PTI-609 was designed after discovering filamin A as the high-affinity target of naltrexone or naloxone. Combined with opiates, ultra-low-dose naloxone or naltrexone can enhance and prolong the analgesia of the opiate alone and prevent or attenuate opioid tolerance, dependence and addictive properties. We will review here the mechanism of action of ultra-low-dose naltrexone and naloxone, the discovery of filamin A as their high-affinity target, and the rationale as to why the current, dualfunction new chemical entity should not only be easier to develop but also more consistently efficacious than opioids combined with ultra-low-dose naltrexone. This new class of compounds, as well as the concept, screening assay and pharmacophore model, are covered in a family of recent patent applications.
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PMID:PTI-609: a novel analgesic that binds filamin A to control opioid signaling. 2072 36