endomorphin-1 and Chronic-Pain

Chronic pain states are clinically relevant and yet unsolved conditions impacting on quality of life and representing an important social and economic burden; these diseases are poorly treated with the currently available drugs, being urgent the need of innovative analgesics. In this frame, novel analogues of endomorphin-1 and dermorphin emerge as promising starting points to develop innovative, more effective analgesics to treat neuropathic pain.. An extensive and structured search of bibliographic databases for peer-reviewed research literature was undertaken using focused review questions; all the retrieved papers were published on prestigious international journals by the experts of the field and were carefully analyzed to collect all the information and data necessary to the conceptual framework of this review.. One hundred papers were included in this review; forty-one defined the up-to-date findings on neuropathic pain etiopathogenesis and its currently available treatment options. Thirty-five papers described all the advantages and drawbacks of using endomorphin-1 (23) or dermorphin (12) in the frame of neuropathic pain and outlined the most relevant advances in developing endomorphin-1 and dermorphin analogs useful as potential, innovative analgesics. Twenty-four papers provided the latest insights into exploiting biased agonism at opioid receptor as an innovative strategy to develop more effective and safer analgesics.. This review reports that innovative opioid peptides will be of great help in better understanding the multifaceted scenario of neuropathic pain treatment, providing very interesting opportunities for the identification of novel and more effective opioid analgesics to be employed as medications.

Topics: Amino Acid Sequence; Analgesics, Opioid; Animals; Chronic Pain; Humans; Ligands; Male; Neuralgia; Oligopeptides; Opioid Peptides; Receptors, Opioid

Endomorphin analogs containing unnatural amino acids have demonstrated potent analgesic effects in our previous studies. In the present study, the differences in antinociception and the mechanisms thereof for analogs 1-3 administered intracerebroventricularly and intrathecally were explored. All analogs at different routes of administration produced potent analgesia compared to the parent peptide endomorphin-1. Multiple antagonists and antibodies were used to explore the mechanisms of action of these analogs, and it was inferred that analogs 1-3 stimulated the μ opioid receptor to induce antinociception. Moreover, the antibody data suggested that analog 2 may induce the release of immunoreactive [Leu

Topics: Analgesics; Animals; Chronic Pain; Dose-Response Relationship, Drug; Dynorphins; Enkephalin, Methionine; Enkephalins; Injections, Intraventricular; Mice; Naloxone; Narcotic Antagonists; Oligopeptides; Receptors, Opioid, mu; Spinal Cord

Clinical studies have shown that schizophrenia is accompanied by hypoalgesia. Accordingly, we have previously reported that a chronic schizophrenia-related rat substrain (Wisket) showed decreased acute heat pain sensitivity. The aim of the present study was to determine the mechanical pain sensitivity and the effects of opioid ligands in a chronic osteoarthritic pain model generated using Wisket rats. Our previous molecular biological studies indicated that the impairment in opioid and cannabinoid receptor functions observed in these animals did not explain their altered pain sensitivity. Therefore, we aimed to investigate another endogenous antinociceptive system, i.e., the oxytocinergic system (which is also implicated in schizophrenia) via the determination the brain-region specific oxytocin receptor mRNA expression in Wisket rats. Osteoarthritis was induced in male adult control Wistar rats without any interventions and in Wisket rats after juvenile social isolation and ketamine treatment. The degree of allodynia and the effects of systemic morphine or intrathecal endomorphin-1 administration were determined. Furthermore, the expression of the oxytocin receptor mRNA was assessed in different brain structures (prefrontal cortex, striatum, diencephalon, brainstem, and olfactory bulb). A lower degree of allodynia was observed in the Wisket group compared with control animals 1 and 2 weeks after the induction of osteoarthritis, which was accompanied by a comparable degree of edema. Systemically or intrathecally applied opioids caused similar time-response curves in both groups, with apparently shorter effects in Wisket animals. The expression of the oxytocin receptor mRNA was lower in most of the brain regions (with the exception of the diencephalon) investigated in Wisket rats vs. the control animals. In summary, both acute and chronic hypoalgesia (as nonspecific symptoms in patients with schizophrenia) can be simulated in Wisket animals as endophenotypes despite the impairment of the endogenous antinociceptive systems evaluated. Thus, this model might be an appropriate tool for further investigation of the molecular basis of altered pain perception in schizophrenia.

Topics: Analgesics, Opioid; Animals; Ankle Joint; Brain; Brain Stem; Chronic Pain; Diencephalon; Disease Models, Animal; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Gene Expression; Hyperalgesia; Iodoacetic Acid; Ketamine; Male; Morphine; Neostriatum; Nociception; Olfactory Bulb; Oligopeptides; Osteoarthritis; Prefrontal Cortex; Rats; Receptors, Oxytocin; RNA, Messenger; Schizophrenia; Social Isolation; Somatosensory Disorders

Topics: Acute Pain; Adult; Chronic Pain; Drug Tolerance; Early Medical Intervention; Humans; Male; Morphine; Morphine Derivatives; Neural Inhibition; Oligopeptides; Opioid-Related Disorders; Pain Management; Peptides, Cyclic; Phenols; Receptors, Opioid, mu; Spinal Cord Stimulation; Tapentadol; Tramadol; Young Adult