Rejected

To study the impact of chronic migraine (CM) on the cognition and quality of life (QoL) of patients in the interictal period, and to analyse the degree of reversibility of any observed alterations following the use of preventive treatment.

Intervertebral disc degeneration (IVDD) has been the major contributor to chronic lower back pain (LBP). Abnormal apoptosis, senescence, and pyroptosis of IVD cells, extracellular matrix (ECM) degradation, and infiltration of immune cells are the major molecular alternations during IVDD. Changes at tissue level frequently occur at advanced IVD tissue. Ectopic ingrowth of nerves within inner annulus fibrosus (AF) and nucleus pulposus (NP) tissue has been considered as the primary cause for LBP. Innervation at IVD tissue mainly included sensory and sympathetic nerves, and many markers for these two types of nerves have been detected since 1940. In fact, in osteoarthritis (OA), beyond pain transmission, the direct regulation of neuropeptides on functions of chondrocytes have attracted researchers' great attention recently. Many physical and pathological similarities between joint and IVD have shed us the light on the neurogenic mechanism involved in IVDD. Here, an overview of the advances in the nervous system within IVD tissue will be performed, with a discussion on in the role of nerve fibers and their neurotransmitters in regulating IVDD. We hope this review can attract more research interest to address neuromodulation and IVDD itself, which will enhance our understanding of the contribution of neuromodulation to the structural changes within IVD tissue and inflammatory responses and will help identify novel therapeutic targets and enable the effective treatment of IVDD disease.

Autologous mesenchymal stem cell neurotrophic factor-secreting cells (NurOwn) have the potential to modify underlying disease mechanisms in progressive multiple sclerosis (PMS).

Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice.

Pain is a prevalent symptom in patients with advanced cancer. Recognition of prognostic factors associated with pain intensity, could help provide better assessment, leading to better pain management.

Nitrous oxide was introduced in The Netherlands as an easily accessible and effective agent for procedural sedation and analgesia (PSA) in children at the Emergency Department. It was expected that its adoption would increase due to the rapid onset of action, limited side effects and the non-invasive character. In this article, we discuss the efficacy and use of nitrous oxide in The Netherlands. Nitrous oxide is a safe and effective agent for children undergoing low-complex procedures. However, the analgesic effect is limited for complex procedures such as fracture reposition, necessitating the use of additional agents such as opioids. Against our expectations, most Dutch Emergency Departments do not use nitrous oxide. Reasons for this are the limited analgesic effects for most procedures, the availability of good alternatives and cost and sustainability considerations.

Sensitive scalp is a common condition defined by the presence of erythema and/or subjective symptoms as pain, pricking, burning, pruritus of the scalp elicited by triggering factors. Trichodynia is a term that describes a sensation of pain or burning of the scalp and was assumed to be part of sensitive scalp. Main goal of the study was to establish the prevalence of sensitive scalp in patients with trichological disorders. We conducted a retrospective observational study recorded: age, sex, trichological disorder (telogen effluvium, androgenetic alopecia, alopecia areata, scarring alopecia, trichotillomania) and scalp symptoms (pruritus, pain, burning and itching sensation). We studied 317 patients. 102 patients (32%) complained of sensitive scalp. Telogen effluvium patients had a significantly higher prevalence of sensitive scalp (p <0.001), pain (p= 0.028), burning sensation (p=0.018), pruritus (p=0.016) and trichodynia (p<0.001) than other patients with alopecias. Likewise, AA patients had a statistically significant higher prevalence of pruritus (p=0.0256) and trichodynia (p=0.0223) than other alopecias patients. Sensitive scalp is a frequent symptom reported by patients with hair loss. Telogen effluvium and alopecia areata seem to be most associated to sensitive scalp.

Oral tablets account for the majority of medications used to acutely treat migraine, but relief can be limited by their rates of dissolution and absorption. The nose is an attractive alternative route of drug delivery since it provides patient convenience of at-home use, gastrointestinal (GI) avoidance, and rapid absorption of drugs into systemic circulation because of its large surface area. However, the site of drug deposition within the nasal cavity should be considered since it can influence drug absorption. Traditional nasal devices have been shown to target drug delivery to the lower nasal space where epithelium is not best-suited for drug absorption and where there is an increased likelihood of drug clearance due to nasal drip, swallowing, or mucociliary clearance, potentially resulting in variable absorption and suboptimal efficacy. Alternatively, the upper nasal space (UNS) offers a permeable, richly vascularized epithelium with a decreased likelihood of drug loss or clearance due to the anatomy of this area. Traditional nasal pumps deposit <5% of active drug into the UNS because of the nasal cavity's complex architecture. A new technology, Precision Olfactory Delivery (POD), is a handheld, manually actuated, propellant-powered, administration device that delivers drug specifically to the UNS. A dihydroergotamine (DHE) mesylate product, INP104, utilizes POD technology to deliver drug to the UNS for the acute treatment of migraine. Results from clinical studies of INP104 demonstrate a favorable pharmacokinetic profile, consistent and predictable dosing, rapid systemic levels known to be effective (similar to other DHE mesylate clinical programs), safety and tolerability on the upper nasal mucosa, and high patient acceptance. POD technology may have the potential to overcome the limitations of traditional nasal delivery systems, while utilizing the nasal delivery benefits of GI tract avoidance, rapid onset, patient convenience, and ease of use.

Migraine is characterized by recurrent episodes of severe headache and has been ranked as the second most disabling medical condition in the world. In frequent or chronic migraine, preventive treatment is recommended; pharmacological, non-pharmacological or a combination of both. Aerobic exercise is an evidence-based alternative to non-pharmacological treatment of migraines and can decrease the number of migraine attacks, intensity, and duration of headaches, as well as increase quality of life. Exercise at a moderate to high intensity level, 3 times a week, 30 minutes, excluding warm up and cool down, is recommended.

A single caudal anaesthetic at the start of lower abdominal surgery is unlikely to provide prolonged analgesia. A second caudal at the end of the procedure extends the analgesia duration but total plasma concentrations may be associated with toxicity. Our aim was to measure total plasma levobupivacaine concentrations after repeat caudal anaesthesia in infants and to generate a pharmacokinetic model for prediction of plasma concentrations after repeat caudal anaesthesia in neonates, infants and children.