Nociceptin/orphanin FQ receptor and pain: Feasibility of the fourth opioid family member.
The pharmacological management of chronic pain is a major therapeutic problem. The need of repeated treatments reduces the usefulness of classical analgesic drugs, like μ opioid receptor (MOP) agonists, characterized by tolerance development, side effects and abuse. Moreover, the pathological persistence of pain modifies nociceptive signals and pain-devoted structure activity weakening MOP agonists and making difficult the research of new active molecules. Nociceptine/orphanin FQ (N/OFQ) and its receptor (NOP) offers a peculiar opioid system able to interact with MOP receptors and made more sensitive by chronic pain conditions. The pain reliever efficacy of NOP agonists against persistent pain, mainly neuropathic pain, has been highlighted after intrathecal infusions in rats and non human primates (NHPs). The differences emerged between the effects of NOP stimulation in rodents and NHPs allow to hypothesize the relevance of NOP modulators in higher organisms strongly encouraging the development of compounds active by a systemic route. Possible applicative perspectives are (i) selective NOP agonists as such, (ii) NOP modulation as adjuvant of MOP-based treatments, or (iii) mixed non-selective agonists vs NOP and classical opioid receptors.
Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. Electronic address: lorenzo.mannelli@unifi.it.
Lorenzo
L
Di Cesare Mannelli
Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Laura
L
Micheli
Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Carla
C
Ghelardini
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D006801:Humans; D018847:Opioid Peptides / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human
Chronic pain; MOP; Morphine; NOP; Neuropathic pain