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Previous studies reported that long-term nociceptive stimulation could result in neurovascular coupling (NVC) dysfunction in brain, but these studies were based mainly on unimodal imaging biomarkers, thus could not comprehensively reflect NVC dysfunction. We investigated the potential NVC dysfunction in chronic migraine by exploring the relationship between neuronal activity and cerebral perfusion maps. The Pearson correlation coefficients between these 2 maps were defined as the NVC biomarkers. NVC biomarkers in migraineurs were significantly lower in left inferior parietal gyrus (IPG), left superior marginal gyrus (SMG) and left angular gyrus (AG), but significantly higher in right superior occipital gyrus (SOG), right superior parietal gyrus (SPG), and precuneus. These brain regions were located mainly in parietal or occipital lobes and were related to visual or sensory information processing. ALFF-CBF in right SPG was positively correlated with disease history and that in right precuneus was negatively correlated with migraine persisting time. fALFF-CBF in left SMG was negatively related to headache frequency and positively related to health condition. fALFF-CBF in left AG was negatively related to headache frequency and positively related to disease history and health condition. In conclusion, multi-modal MRI could be used to detect NVC dysfunction in chronic migraine patients, which is a new method to assess the impact of chronic pain to the brain.
New treatments for stress-related disorders including depression, anxiety and Substance Use Disorder are greatly needed. Kappa opioid receptors (KORs) are expressed in central nervous system, including areas implicated in analgesia and affective state. Although KOR agonists share the antinociceptive effects of mu opioid receptor (MOR) agonists, they also tend to produce negative affective states. In contrast, selective KOR antagonists have antidepressant- and anxiolytic-like effects, stimulating interest in their therapeutic potential. The prototypical KOR antagonists (e.g., norBNI, JDTic) have an exceptionally long duration of action that complicates their use in humans, particular in tests to establish safety. This study was designed to test dose- and time-course effects of novel KOR antagonists with the goal of identifying short-acting lead compounds for future medication development.
Newborn infants are vulnerable to procedural stress and pain exposure on the first weeks of life that represents a critical period for the development of nociceptive, sensory, emotional, and social functions. We evaluated the nociceptive behavior of adult male and female rats that were submitted to nociceptive experience in the neonatal period and the maternal behavior in the postnatal period.
Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue, and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole-genome sequencing. When comparing FM patients with unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM. In line with observed alteration in butyrate-metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients. Using machine-learning algorithms, the microbiome composition alone allowed for the classification of patients and controls (receiver operating characteristic area under the curve 87.8%). To the best of our knowledge, this is the first demonstration of gut microbiome alteration in nonvisceral pain. This observation paves the way for further studies, elucidating the pathophysiology of FM, developing diagnostic aids and possibly allowing for new treatment modalities to be explored.
Wnt signaling pathway has been investigated extensively for its diverse metabolic and pain modulating mechanisms and recently its involvement has been postulated in the development of neuropathic pain. However, there are no reports as yet on involvement of Wnt signaling pathway in one of the most debilitating neurovascular complication of diabetes, i.e, diabetic peripheral neuropathy (DPN). Thus, in the present study, involvement of Wnt signaling was investigated in DPN using Wnt signaling inhibitors namely LGK974 (Porcupine inhibitor), NSC668036 (Disheveled inhibitor) and PNU74654 (β-catenin inhibitor). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) to male Sprague Dawley rats. Diabetic rats after six weeks of diabetes induction showed increased expression of Wnt signaling proteins in the spinal cord (L4-L6 lumbar segment), dorsal root ganglions (DRGs) and sciatic nerves. Subsequent increase in inflammation, endoplasmic reticulum (ER) stress and loss of intraepidermal nerve fiber density (IENFD) was also observed, leading to neurobehavioral and nerve functional deficits in diabetic rats. Intrathecal administration of Wnt signaling inhibitors (each at doses of 10 and 30 µM) in diabetic rats showed improvement in pain-associated behaviors (heat, cold & mechanical hyperalgesia) and nerve functions (motor, sensory nerve conduction velocities and nerve blood flow) by decreasing the expression of Wnt pathway proteins, inflammatory marker, matrix metalloproteinase 2 (MMP2), ER stress marker, glucose-regulated protein 78 (GRP78) and improving IENFD. All these results signify the neuroprotective potential of Wnt signaling inhibitors in DPN. Perspective: This study emphasizes the involvement of Wnt signaling pathway in diabetic peripheral neuropathy (DPN). Blockade of this pathway using Wnt inhibitors provided neuroprotection in experimental DPN in rats. This study may provide a basis for exploring the therapeutic potential of Wnt inhibitors in DPN patients.
Diagnostic testing is of limited value among patients with migraine who present to an emergency department. Various nonopioid, disease-specific treatments are available for patients who present to an emergency department with migraine headache and associated features. Emergency physicians should recognize that the acute migraine presentation is part of an underlying disorder; care should be geared to the underlying headache disorder in addition to the acute attack.
Astrocytes are critical for maintaining the homeostasis of the CNS. Increasing evidence suggests that a number of neurological and neuropsychiatric disorders, including chronic pain, may result from astrocyte 'gliopathy'. Indeed, in recent years there has been substantial progress in our understanding of how astrocytes can regulate nociceptive synaptic transmission via neuronal-glial and glial-glial cell interactions, as well as the involvement of spinal and supraspinal astrocytes in the modulation of pain signalling and the maintenance of neuropathic pain. A role of astrocytes in the pathogenesis of chronic itch is also emerging. These developments suggest that targeting the specific pathways that are responsible for astrogliopathy may represent a novel approach to develop therapies for chronic pain and chronic itch.
Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. This disease should be viewed as a public health problem with a major effect on the quality of life of women as well as being a substantial economic burden. In light of the considerable progress with diagnostic imaging (for example, transvaginal ultrasound and MRI), exploratory laparoscopy should no longer be used to diagnose endometriotic lesions. Instead, diagnosis of endometriosis should be based on a structured process involving the combination of patient interviews, clinical examination and imaging. Notably, a diagnosis of endometriosis often leads to immediate surgery. Therefore, rethinking the diagnosis and management of endometriosis is warranted. Instead of assessing endometriosis on the day of the diagnosis, gynaecologists should consider the patient's 'endometriosis life'. Medical treatment is the first-line therapeutic option for patients with pelvic pain and no desire for immediate pregnancy. In women with infertility, careful consideration should be made regarding whether to provide assisted reproductive technologies prior to performing endometriosis surgery. Modern endometriosis management should be individualized with a patient-centred, multi-modal and interdisciplinary integrated approach.
Couple interventions for chronic pain have been shown to more effectively reduce pain intensity for individuals with chronic pain (ICPs) than individual behavioral interventions or usual care. This systematic review identifies randomized controlled trials (RCTs) of couple interventions to highlight strategies that could be incorporated into psychotherapy with ICPs and their romantic partners.