Uncovering the analgesic effects of a pH-dependent mu-opioid receptor agonist using a model of non-evoked ongoing pain.

  title={Uncovering the analgesic effects of a pH-dependent mu-opioid receptor agonist using a model of non-evoked ongoing pain.},
  author={Nicolas Massaly and Julia Temp and Halina Machelska and Christoph Stein},
Currently, opioids targeting mu-opioid receptors (MOR) are the most potent drugs for acute and cancer pain. However, opioids produce adverse side effects such as constipation, respiratory depression, or addiction potential. We recently developed (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), a compound that does not evoke central or intestinal side effects due to its selective activation of MOR at low pH in peripheral injured tissues. While we demonstrated that NFEPP… 
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Results extend the range of conditions across which pain-related manipulations fail to increase opioid seeking in rats and suggest that enhanced opioid-addiction risk in humans with chronic pain involves factors other than enhanced opioid reinforcement and relapse.
Modelling altered signalling of G-protein coupled receptors in inflamed environment to advance drug design
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Pain and Opioid Use in Cancer Survivors: A Practical Guide to Account for Perceived Injustice.
Clinicians are advised to screen for perceived injustice in patients with pain following cancer treatment and Therapeutic targeting of perceived injustice can be done through an approach comprising of modified pain neuroscience education, motivational interviewing, and acceptance-based interventions.
A low pKa ligand inhibits cancer-associated pain in mice by activating peripheral mu-opioid receptors
The increased affinity of NFEPP for murine MOR at low pH, and its ability to inhibit bone cancer-induced hyperalgesia through peripheral MOR are demonstrated.


Analgesic effects of a novel pH-dependent μ-opioid receptor agonist in models of neuropathic and abdominal pain
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Chronic Pain Induces Anxiety with Concomitant Changes in Opioidergic Function in the Amygdala
The present data constitute the first evidence that chronic pain has an anxiogenic effect in mice and may be associated with changes in opioidergic function in the amygdala.
Direct Evidence for the Involvement of the Mesolimbic κ-Opioid System in the Morphine-Induced Rewarding Effect Under an Inflammatory Pain-Like State
Findings suggest that the inflammatory pain-like state induced by formalin injection may have caused a sustained activation of the κ-opioidergic system within the N.Acc.
Activation of Peripheral &mgr;-opioid Receptors by Dermorphin [D-Arg2, Lys4] (1–4) Amide Leads to Modality-preferred Inhibition of Neuropathic Pain
Findings suggest that DALDA may represent a potential alternative to current opioid therapy for the treatment of neuropathic pain and is likely to be associated with minimal adverse effects.
Effects of acute and repeated treatment with the biased mu opioid receptor agonist TRV130 (oliceridine) on measures of antinociception, gastrointestinal function, and abuse liability in rodents
The results suggest that TRV130 retains undesirable constipating and abuse-related effects during repeated treatment despite its bias for G-protein signaling.
Kappa Opioid Receptors Drive a Tonic Aversive Component of Chronic Pain
It is shown that KORs are sufficient to drive the tonic-aversive component of chronic pain; the emotional component of pain that is argued to significantly impact a patient's quality of life.
A nontoxic pain killer designed by modeling of pathological receptor conformations
A novel opioid receptor agonist that, unlike clinically used opioids, best activates the receptors in such acidified tissues and produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation,constipation, constipation, or addiction potential.
Kappa opioid signaling in the central nucleus of the amygdala promotes disinhibition and aversiveness of chronic neuropathic pain
Testing the hypothesis that KOR circuits in the central nucleus of the amygdala (CeA) undergo neuroplasticity in chronic neuropathic pain resulting in increased sensory and affective pain responses found that nor-BNI eliminated the aversiveness of ongoing pain.
Lateralized kappa opioid receptor signaling from the amygdala central nucleus promotes stress-induced functional pain
After priming, stress-induced dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws, likely reflecting enhanced descending facilitation that masks descending inhibition.
Central Sensitization and Neuropathic Features of Ongoing Pain in a Rat Model of Advanced Osteoarthritis.