Rejected

Chronic pain is a relevant health condition affecting one out of five individuals that is often not adequately treated by currently available analgesics. This, together with the dramatic increase in addicted people within the dramatic "opioid epidemics," significantly spurs the quest for innovative analgesics provided with increased efficacy, reduced abuse liability, and fewer adverse effects.Within this frame, biased agonists at opioid receptors have attracted increasing interest in the last decade as they have emerged as more effective and safer candidate analgesics.In this chapter, promises, pitfalls, and future perspective of biased agonists at mu (MOR) and kappa (KOR) opioid receptors are discussed. Moreover, methodological insights are provided with regard to the most appropriate experimental settings to be employed aiming at developing novel biased KOR agonists.

Poor sleep quality is associated with a decrease in quality of life in patients with major burn scars, combined with pruritus and pain. Few interventions have been reported to improve the sleep quality of patients with scars. In the current prospective cohort study, we investigated the efficacy of CO-ablative fractional laser (AFL) surgery conventional surgery in post-burn patients with hypertrophic scars with sleep quality as the primary study outcome.

Patient ownership of disease is vital in rare diseases like primary biliary cholangitis (PBC). This survey of UK members of the PBC foundation aimed to assess patients' perception of their disease management, focusing on key biomarkers and problematic symptoms.

Fibromyalgia (FM) is a complex pain syndrome accompanied by physical disability and loss of daily life activities. Evidences suggest that modulation of the primary motor cortex (M1) by transcranial direct current stimulation (tDCS) improves functional physical capacity in chronic pain conditions. However, the gain on physical function in people living with FM receiving tDCS is still unclear. This study aimed to evaluate whether the tDCS task-oriented approach improves function and reduces pain in a single cohort of 10 FM. A total of 10 women with FM (60.4 ± 15.37 years old) were enrolled in an intervention including anodal tDCS delivered on M1 (2 mA from a constant stimulator for 20 min); simultaneously they performed a functional task. The anode was placed on the contralateral hemisphere of the dominant hand. Outcome assessments were done before the stimulation, immediately after stimulation and 30 min after the end of tDCS. The same protocol was applied in subsequent sessions. A total of five consecutive days of tDCS were completed. The main outcomes were the number of repetitions achieved and time in active practice to evaluate functional physical task performance such as intensity of the pain (visual analog scale) and level of fatigue (Borg scale). After 5 days of tDCS, the number of repetitions achieved significantly increased by 49% ( = 0.012). No change was observed in active practice time. No increase in pain was observed despite the mobility of the painful parts of the body. These results are encouraging since an increase in pain due to the mobilization of painful body parts could have been observed at the end of the 5th day of the experiment. These results support the use of tDCS in task-based rehabilitation.

Death by suicide is a global epidemic with over 800 K suicidal deaths worlwide in 2012. Suicide is the 10th leading cause of death among Americans and more than 44 K people died by suicide in 2019 in the United States. Patients with chronic pain, including, but not limited to, those with substance use disorders, are particularly vulnerable. Chronic pain patients have twice the risk of death by suicide compared to those without pain, and 50% of chronic pain patients report that they have considered suicide at some point due to their pain. The kappa opioid system is implicated in negative mood states including dysphoria, depression, and anxiety, and recent evidence shows that chronic pain increases the function of this system in limbic brain regions important for affect and motivation. Additionally, dynorphin, the endogenous ligand that activates the kappa opioid receptor is increased in the caudate putamen of human suicide victims. A potential treatment for reducing suicidal ideation and suicidal attempts is buprenorphine. Buprenorphine, a partial mu opioid agonist with kappa opioid antagonist properties, reduced suicidal ideation in chronic pain patients with and without an opioid use disorder. This review will highlight the clinical and preclinical evidence to support the use of buprenorphine in mitigating pain-induced negative affective states and suicidal thoughts, where these effects are at least partially mediated via its kappa antagonist properties.

Neurological presentation of COVID-19 is increasingly being recognised. Cranial neuropathy in COVID-19 is an uncommon and under-diagnosed entity. We report a case series of 4 patients who presented with trigeminal neuropathy (two cases) and facial nerve palsy (two cases) which recovered with conservative treatment along with the review of the literature.

Glutamic acid decarboxylase (GAD) antibodies are associated with disabling conditions such as stiff person syndrome, temporal lobe epilepsy (TLE), limbic encephalitis, cerebellar ataxia (CA), and ocular movement disorders, which are usually chronic and difficult to treat. GAD-related TLE has poor response to anti-seizure medications and immune therapies, and epilepsy surgery is rarely successful. We report on a 47-year-old female with history of migraine, autoimmune thyroid disease, ankylosing spondylitis, and drug-resistant TLE. A video electroencephalography recorded frequent seizures with temporo-insular semiology, correlating to left temporal epileptiform activity and left mesiotemporal hyperintensity on magnetic resonance imaging. GAD autoimmunity was confirmed by very high GAD antibody titers in serum and cerebrospinal fluid. Steroids, immunoglobulins, and cyclophosphamide had no effect, and selective left amygdalectomy was performed based on very restricted hypermetabolism on positron-emission tomography. After transient seizure freedom, significant epilepsy improvement was observed in spite of memory decline. Transient worsening was noted 1 year later during diabetes mellitus manifestation and 5 years later during presentation of progressive CA, which stabilized on rituximab treatment. We believe this case illustrates the diversity and the frequent overlap of GAD-associated disorders, the need of early and aggressive immunotherapy in severe patients, as well as the possible benefit from epilepsy surgery in some GAD-TLE.

Visual hallucinations (VHs) in Parkinson's disease (PD) are the cardinal symptoms which declare the onset of PD psychosis (PDP). The anthropomorphic and zoomorphic VHs of PD resemble those of Charles Bonnet syndrome and temporal lobe epilepsy. In both of these disorders electroencephalography (EEG) abnormalities have been described. We therefore sought to examine whether VHs in PD were associated with similar EEG abnormalities. This retrospective observational study searched the medical records of 300 PD patients and filtered for those containing clinical 20-min scalp EEGs. Remaining records were separated into two groups: patients with reported VHs and those without. The prevalence of epileptiform discharges in the EEGs of both groups was identified. Epileptiform discharges were present in 5 of 13 (38.5%) PD patients with VHs; all localized to the temporal lobe. No epileptiform discharges were observed in the EEGs of the 31 PD patients without VHs. The significantly high incidence of temporal lobe epileptiform discharges in PD patients with VHs as compared to those without VHs lends to the possibility of an association visual cortex epileptogenic focus. Accordingly, for treatment-refractory patients, antiepileptic drugs might be considered, as in the case of Charles Bonnet syndrome, temporal lobe epilepsy and migraine with visual aura. Future prospective studies involving larger samples and multi-center cohorts are required to validate these observational findings.

Pain is often presumed to be part of the sport injury experience. The time-loss definition of injury leads to under-reported athletic pain impacting performance and quality of life. Whilst research regarding the assessment and classification of back pain in athletes is emerging, little has been reported regarding how peripheral pain is assessed and classified in research and practice. Six databases will be searched for relevant articles. Title and abstract screening followed by full-text screening will be completed by two independent reviewers. Data charting will be carried out using a modified standardised form. Descriptive results and frequencies will be reported. Pain measures identified in the studies will be mapped against the IOC Athlete Pain Framework alongside a narrative summary. Published peer-reviewed primary research studies alongside systematic reviews and clinical practice guidelines reporting the assessment or classification of pain in athletes of any age with chronic or acute peripheral pain across all study contexts in the English language on human participants from inception of the databases will be included. The results of this study are part of a body of research which will be used to inform the development of a pain assessment framework. The scoping review will be submitted for peer-reviewed journal publication and presented at sports medicine conferences. This review will inform researchers and clinicians working with athletes in pain how pain assessment and classification is currently conducted and positioned against the IOC Athlete Pain Framework.

Focused ultrasound (FUS) is a potential tool for treating chronic pain by modulating the central nervous system. Herein, we aimed to determine whether transcranial FUS stimulation of the anterior cingulate cortex (ACC) effectively improved chronic pain in the chronic compress injury mice model at different stages of neuropathic pain. The mechanical threshold of pain was recorded in the nociceptive tests. We found FUS stimulation elevated the mechanical threshold of pain in both short-term ( < 0.01) and long-term ( < 0.05) experiments. Furthermore, we determined protein expression differences in ACC between the control group, the intervention group, and the Sham group to analyze the underlying mechanism of FUS stimulation in improving neuropathic pain. Additionally, the results showed FUS stimulation led to alterations in differential proteins in long-term experiments, including cellular processes, cellular signaling, and information storage and processing. Our findings indicate FUS may effectively alleviate mechanical neuropathic pain via the ACC's stimulation, especially in the chronic state.