Accepted

Functional somatic syndromes are increasingly diagnosed in chronically ill patients presenting with an array of symptoms not attributed to physical ailments. Conditions such as chronic fatigue syndrome, fibromyalgia syndrome, or irritable bowel syndrome are common disorders that belong in this broad category. Such syndromes are characterised by the presence of one or multiple chronic symptoms including widespread musculoskeletal pain, fatigue, sleep disorders, and abdominal pain, amongst other issues. Symptoms are believed to relate to a complex interaction of biological and psychosocial factors, where a definite aetiology has not been established. Theories suggest causative pathways between the immune and nervous systems of affected individuals with several risk factors identified in patients presenting with one or more functional syndromes. Risk factors including stress and childhood trauma are now recognised as important contributors to chronic pain conditions. Emotional, physical, and sexual abuse during childhood is considered a severe stressor having a high prevalence in functional somatic syndrome suffers. Such trauma permanently alters the biological stress response of the suffers leading to neuroexcitatory and other nerve issues associated with chronic pain in adults. Traumatic and chronic stress results in epigenetic changes in stress response genes, which ultimately leads to dysregulation of the hypothalamic-pituitary axis, the autonomic nervous system, and the immune system manifesting in a broad array of symptoms. Importantly, these systems are known to be dysregulated in patients suffering from functional somatic syndrome. Functional somatic syndromes are also highly prevalent co-morbidities of psychiatric conditions, mood disorders, and anxiety. Consequently, this review aims to provide insight into the role of the nervous system and immune system in chronic pain disorders associated with the musculoskeletal system, and central and peripheral nervous systems.

High-voltage-activated calcium channels (HVACCs) are promising targets for developing analgesics given their roles in controlling synaptic transmission, neuronal excitability and neuropeptide release in primary nociceptive neurons. Despite previous efforts in developing HVACCs inhibitors of various drug modalities, it remains undetermined whether targeting HVACCs directly by a gene therapy approach could lead to pain alleviation in vivo. To test this, Sun and colleagues adopted a post-translational ubiquitination-based knockdown method targeting HVACCs in primary sensory neurons. They showed ablation of HVACC currents in a subset of primary sensory neurons, dampened hyperexcitability of sensory neurons after nerve injury and reduced pain behavior with no apparent adverse effects [1]. The results open the possibility of targeting ion channels with ubiquitination-based knockdown as a promising gene therapy candidate for pain treatment in future clinical studies.

Neurovascular compression (NVC) has been the primary hypothesis for the underlying mechanism of classical trigeminal neuralgia (TN). However, a substantial body of literature has emerged highlighting notable exceptions to this hypothesis. The purpose of this study is to assess the reliability and diagnostic accuracy of high resolution, high contrast MRI-determined neurovascular contact for TN.

Spinal cord stimulation (SCS) is a last-resort treatment for patients with chronic neuropathic pain. The mechanism underlying SCS and pain relief is not yet fully understood. Because the inflammatory balance between pro- and anti-inflammatory molecules in the spinal nociceptive network is pivotal in the development and maintenance of neuropathic pain, the working mechanism of SCS is suggested to be related to the modulation of this balance. The aim of this systematic review is to summarize and understand the effects of different SCS paradigms on the central inflammatory balance in the spinal cord.

To investigate the effect of prolonged low-level laser therapy application combined with exercise on pain and disability in patients with osteoarthritis of the knee.

Neurological disorders such as Alzheimer's disease, Parkinson's disease, dementia, epilepsy, depression, migraine etc. are affecting more and more elderly people's day by day. Conventional route of administration to treat these diseases has to face a major hindrance that is blood brain and blood- (CSF) barrier to achieve desired concentration of drug at the site of action for therapeutic effect. Hence, intranasal route of delivery is considered as promising and alternative route to achieve desired goals. In last four decades, brain targeting strategies are widely studied and considered having great potential by researchers; especially intranasal delivery owing to its benefits. Various nano formulations such as nanoemulsions, nanosuspensions, hydrogels, in situ gels, dendrimers and lipidic formulations are studied widely. Lipid nano formulations especially second generation nanostructured lipid carriers offer greater advantages in terms of stability, fabrication techniques, scalability, drug loading and drug targeting. Nanostructured lipid carrier (NLCs) constitute of two major components viz solid lipid and liquid lipid in a specific ratio. In this review, authors have discussed about the possible synergistic actions of oils/liquid lipids with synthetic drugs resulting into great therapeutic benefits.

Medical child abuse (MCA), previously referred to as Munchausen by proxy, can present as chronic pain. We report the presentation of five children seeking treatment for chronic pain who we identified as victims of MCA. The index case had essentially not eaten for the 6 years of her life due to alleged allergies to all foods, developed severe pain, used a wheelchair for ambulation beyond a few blocks, and was alleged to have dysautonomia requiring oxygen monitoring at night. Other cases posed as arthritis that resulted in foot amputation and total body pain, fibromyalgia with alleged mutation negative Stickler syndrome who had symptoms only in her mother's presence, severe incapacitating intermittent pains along with abdominal pain that resulted in appendectomy, cholecystectomy, and pancreatectomy, and alleged disabling hypermobile Ehlers-Danlos in a non-hypermobile child for which the mother sought a power wheelchair. The unusual pattern to the pain, the presence of multiple additional, atypical symptoms and diagnoses, and a generally well appearing child are characteristic. The perpetrator is typically over-invested in the symptoms, derives tangible and intangible secondary gain from the child's alleged illnesses, and is able to present the child in such a fashion to enlist the physician to aid in perpetuating the abuse. These children are highly over-medicalized and suffer significant morbidity. Multiple barriers exist to identifying and reporting these children to Child Protective Services, which need to be recognized and overcome in order to protect these vulnerable children.