Accepted

Migraine is a disabling neurovascular disorder, characterized by moderate to severe unilateral headaches, nausea, photophobia, and/or phonophobia, with a higher prevalence in women than in men, which can drastically affect the quality of life of migraine patients. In addition, this chronic disorder is related with metabolic comorbidities associated with the patient's lifestyle, including obesity and diabetes mellitus (DM). Beyond the personal and socioeconomic impact caused by migraine, obesity and DM, it has been suggested that these metabolic disorders seem to be related to migraine since: (i) they are a risk factor for developing cardiovascular disorders or chronic diseases; (ii) they can be influenced by genetic and environmental risk factors; and (iii) while clinical and epidemiological studies suggest that obesity is a risk factor for migraine, DM (i.e., type 1 and type 2 DM) have been reported to be either a protective or a risk factor in migraine. On this basis, and given the high worldwide prevalence of migraine, obesity, and DM, this article provides a narrative review of the current literature related to the association between the etiology and pathophysiology of migraine and these metabolic disorders, considering lifestyle aspects, as well as the possible involvement of neurotransmitters, neuropeptides, and/or sex hormones. While a link between migraine and metabolic disorders has been suggested, many studies are contradictory and the mechanisms involved in this association are not yet sufficiently established. Therefore, further research should be focused on understanding the possible mechanisms involved.

The most common cause of chronic musculoskeletal pain is chronic myofascial pain syndrome (MPS). MPS often presents with increased muscle stiffness, and the myofascial trigger point (MTrP). Imaging modalities have been used to identify the MTrP, but their role in the detection and diagnosis of MPS remains unclear. The purpose of this review was to identify evidence in literature for the use of imaging in the role of classifying and explaining the physiology of MTrPs. Since few imaging techniques have been performed on MTrPs, we explored the imaging techniques that can effectively image complex skeletal muscle microstructure, and how they could be used. As part of a scoping review, we conducted a systematic search from three medical databases (CINAHL, EMBASE and MEDLINE) from year to year to analyze past MTrP imaging, as well as analyzing imaging techniques performed on the microstructure of muscle. Previously, ultrasound has been used to differentiate active, latent MTrPs, but these studies do not adequately address their underlying anatomical structure. MRI remains the standard method of imaging skeletal muscle. The existing MRI literature suggests that the DTI technique can quantify muscle injury, strain, and structure. However, theoretically, HARDI and DKI techniques seem to provide more information for complex structural areas, although these modalities have a disadvantage of longer scan times and have not been widely used on skeletal muscle. Our review suggests that DTI is the most effective imaging modality that has been used to define the microstructure of muscle and hence, could be optimal to image the MTrP. HARDI and DKI are techniques with theoretical potential for analysis of muscle, which may provide more detailed information representative of finer muscle structural features. Future research utilizing MRI techniques to image muscle are necessary to provide a more robust means of imaging skeletal muscle and the MTrP.

Pain plays an indispensable role as an alarm system to protect us from dangers or injuries. However, neuropathic pain, a debilitating pain condition caused by damage to the nervous system, persists for a long period even in the absence of dangerous stimuli or after injuries have healed. In this condition, pain becomes a disease itself rather than the alarm system and is often resistant to currently available medications. A growing body of evidence indicates that microglia, a type of macrophages residing in the central nervous system, play a crucial role in the pathogenesis of neuropathic pain. Whenever microglia in the spinal cord detect a damaging signal within the nervous system, they become activated and cause diverse alterations that change neural excitability, leading to the development of neuropathic pain. For over a decade, several lines of molecular and cellular mechanisms that define microglial activation and subsequently altered pain transmission have been proposed. In particular, P2X4 receptors (a subtype of purinergic receptors) expressed by microglia have been investigated as an essential molecule for neuropathic pain. In this review article, we describe our understanding of the mechanisms by which activated microglia cause neuropathic pain through P2X4 receptors, their involvement in several pathological contexts, and recent efforts to develop new drugs targeting microglia and P2X4 receptors.

Musculoskeletal pain (excluding bone cancer pain) affects more than 30% of the global population and imposes an enormous burden on patients, families, and caregivers related to functional limitation, emotional distress, effects on mood, loss of independence, and reduced quality of life. The pathogenic mechanisms of musculoskeletal pain relate to the differential sensory innervation of bones, joints, and muscles as opposed to skin and involve a number of peripheral and central nervous system cells and mediators. The interplay of neurons and non-neural cells (e.g. glial, mesenchymal, and immune cells) amplifies and sensitizes pain signals in a manner that leads to cortical remodeling. Moreover, sex, age, mood, and social factors, together with beliefs, thoughts, and pain behaviors influence the way in which musculoskeletal pain manifests and is understood and assessed. The aim of this narrative review is to summarize the different pathogenic mechanisms underlying musculoskeletal pain and how these mechanisms interact to promote the transition from acute to chronic pain.