SUMMARYWhat is known and objective: Chronic pain presents a difficult clinical challenge because of the limited efficacy, the limiting adverse-effect profile or the abuse potential of current analgesic options. Cebranopadol is a novel new agent in clinical trials that combines dual agonist action at opioid and nociceptin/orphanin FQ peptide (NOP) receptors. It is the first truly unique, centrally acting analgesic in several years. We here review the basic and clinical pharmacology of cebranopadol. Methods: Published literature and Internet sources were searched to identify information related to the basic science (pharmacology and medicinal chemistry) and development (clinical trial) information on the mechanism of dual opioid and NOP receptor pharmacologic action in general, and for cebranopadol in particular. The identified sources were reviewed and the information synthesized. Results: The preclinical testing of cebranopadol has characterized it as a dual opioid and NOP receptor agonist that displays antinociceptive and antihyperalgesic action in a variety of acute and chronic pain models in animals. Unlike most current traditional opioids, it is generally more potent against neuropathic than nociceptive pain. Several phase 2 clinical trials have been completed. What is new and conclusion: Despite the medical need, a truly novel centrally acting analgesic has not been developed in many years. Cebranopadol represents a truly novel mechanistic approach. Its actual place in pain pharmacotherapy awaits the results of phase 3 clinical trials.
Background Chronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment. Objective Characterize the presence and distribution of pain, myofascial dysfunction and sensitisation beyond the pelvis in women with endometriosis‐associated chronic pelvic pain. Methods Cross‐sectional study of 30 women prior to participation in a clinical trial. Evaluation included pain‐focused abdominopelvic gynaecologic examination with the identification of pelvic floor muscle spasm. Neuro‐musculoskeletal examination assessed paraspinal allodynia and hyperalgesia bilaterally and myofascial trigger points in 13 paired muscles. Pressure‐pain thresholds were measured over interspinous ligaments and trigger points. Women completed the body territories element of the Body Pain Index. Results All women had a pelvic floor muscle spasm that they self‐identified as a major focus of pain. Twenty of 30 women described their pelvic pain as focal. However, all demonstrated widespread myofascial dysfunction with low pressure‐pain thresholds and trigger points in over two‐thirds of 26 assessed regions. Widespread spinal segmental sensitisation was present in 17/30, thoracic in 21/30 and lumbosacral/pelvic in 18/30. Cervical sensitisation manifested as low pressure‐pain thresholds with 23/30 also reporting recurrent, severe headaches and 21/30 experiencing orofacial pain. Those reporting diffuse pelvic pain were more likely to have widespread (p = .024) and lumbosacral/pelvic (p = .036) sensitisation and report over 10 painful body areas (p = .009). Conclusions Women with endometriosis‐associated chronic pelvic pain often have myofascial dysfunction and sensitisation beyond the pelvic region that may be initiated or maintained by on‐going pelvic floor spasm. These myofascial and nervous system manifestations warrant consideration when managing pain in this population. Clinicaltrials.gov identifier: NCT01553201. Significance Women with endometriosis often have pelvic pain persisting after surgery despite hormonal therapies and these women have regional pelvic sensitisation and myofascial dysfunction. Pelvic floor muscle spasm is a major pain focus in this population. Sensitisation and myofascial dysfunction are widespread, beyond the pelvic region. On‐going pelvic floor spasm may initiate or maintain sensitisation. Myofascial/sensitisation manifestations warrant consideration when managing pain in this population.
There is currently confusion surrounding the phenotype of and diagnostic criteria for myofascial pain syndrome (MPS) in the published literature. This narrative literature review investigated whether there is consensus regarding the descriptive terminology used for MPS and the trend of MPS publications over time. The phrase “myofascial pain syndrome” was used to search PubMed and Web of Science, returning 923 articles. Of these, we included only full‐text, primary research articles containing “myofascial pain syndrome” in the title, reducing the total articles reviewed to 167. We identified 116 descriptors and categorized them under one of five clusters that shared similar findings and are commonly associated with MPS: “trigger points,” “muscle,” “pain,” “nervous system,” and “fascia.” The frequency of the clinical criteria of Travell and Simons was tabulated. Terms pertaining to the clusters “trigger points,” “muscle,” or “pain” appeared in approximately 90% of the articles; “nervous system” in 46%; and “fascia” in 20%. Only 42% used the criteria of Travell and Simons. Most articles (122) included a combination of three or four clusters to describe MPS. In addition, MPS publications have doubled since 2010 compared to the prior decade. The publication patterns, determined by changes in which specialty journals articles on MPS have been published, have shifted from investigational to intervention studies. This may have been influenced by heterogeneity in the usage of MPS terminology. This underscores the lack of a reliable MPS diagnosis and limits human subjects research. Improved consistency in terminology is needed to establish consensus within the field and to inform future research studying the pathophysiology of MPS.
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