Browse by Audience
Opioids are the frontline analgesics for managing various types of pain. Paradoxically, repeated use of opioid analgesics may cause an exacerbated pain state known as opioid-induced hyperalgesia (OIH), which significantly contributes to dose escalation and consequently opioid overdose. Neuronal malplasticity in pain circuits has been the predominant proposed mechanism of OIH expression. Although glial cells are known to become reactive in OIH animal models, their biological contribution to OIH remains to be defined and their activation mechanism remains to be elucidated. Here, we show that reactive astrocytes (a.k.a. astrogliosis) are critical for OIH development in both male and female mice. Genetic reduction of astrogliosis inhibited the expression of OIH and morphine-induced neural circuit polarization (NCP) in the spinal dorsal horn (SDH). We found that Wnt5a is a neuron-to-astrocyte signal that is required for morphine-induced astrogliosis. Conditional knock-out of Wnt5a in neurons or its co-receptor ROR2 in astrocytes blocked not only morphine-induced astrogliosis but also OIH and NCP. Furthermore, we showed that the Wnt5a-ROR2 signaling-dependent astrogliosis contributes to OIH via inflammasome-regulated IL-1β. Our results reveal an important role of morphine-induced astrogliosis in OIH pathogenesis and elucidate a neuron-to-astrocyte intercellular Wnt signaling pathway that controls the astrogliosis.
Learn More >Several recent studies have established the efficacy of photobiomodulation therapy (PBMT) in painful clinical conditions. Diabetic neuropathy (DN) can be related to activating mitogen-activated protein kinases (MAPK), such as p38, in the peripheral nerve. MAPK pathway is activated in response to extracellular stimuli, including interleukins TNF-α and IL-1β. We verified the pain relief potential of PBMT in streptozotocin (STZ)-induced diabetic neuropathic rats and its influence on the MAPK pathway regulation and calcium (Ca) dynamics. We then observed that PBMT applied to the L4-L5 dorsal root ganglion (DRG) region reduced the intensity of hyperalgesia, decreased TNF-α and IL-1β levels, and p38-MAPK mRNA expression in DRG of diabetic neuropathic rats. DN induced the activation of phosphorylated p38 (p-38) MAPK co-localized with TRPV1 neurons; PBMT partially prevented p-38 activation. DN was related to an increase of p38-MAPK expression due to proinflammatory interleukins, and the PBMT (904 nm) treatment counteracted this condition. Also, the sensitization of DRG neurons by the hyperglycemic condition demonstrated during the Ca dynamics was reduced by PBMT, contributing to its anti-hyperalgesic effects.
Learn More >The treatment of patients with headache represents an important part of a neurologist's activity. It requires sufficient training for neurology residents. In France, residents in neurology can complete this training by attending specialized consultations or by participating in a postgraduate training program called "Diplôme Inter-Universitaire Migraine et Céphalées" (DIUMC).
Learn More >Temporomandibular disorders (TMD) symptoms develop into chronic pain for some patients, but the reasons for this are unclear. Psychosocial factors and chronic overlapping pain conditions are believed to contribute to the development of pain-related disability. We examined the role of jaw function, negative and positive psychological factors, chronic overlapping pain conditions (COPCs) on pain-related disability while controlling for demographic variables. We collected demographics, medical and psychosocial history, and the Graded Chronic Pain Scale, a measure of pain intensity and pain interference from 400 participants with chronic TMD. Structural equation modeling was used to assess a model of of COPCs and the latent variables of psychological unease (pain catastrophizing, somatic symptoms, and negative affect), positive valence factors (optimism and positive affect), jaw function (chewing, opening, and expression limitation), and pain-related disability (pain intensity and pain interference) while controlling for demographic variables. We achieved good fit of a parsimonious model (root-mean-square error of approximation = .063 (90% CI) [.051-.075]), comparative fit index =.942, standard root-mean-square residual = .067). Jaw function was the strongest latent variable predictor, followed by psychological unease and COPCs suggesting resources focused on improving joint function, psychosocial support, and management of COPCs will improve pain-related disability in TMDs. These findings not only increase the body of knowledge related to TMD clinical phenotypes but also, have translational impact in further supporting the potential value of targeting physical therapy such as jaw exercise along with psychological interventions as multidisciplinary nonpharmacological therapeutic solutions.
Learn More >Disk herniation is a primary cause of radicular back pain. The purpose of this study was to evaluate the antiallodynic effective dose in 50% of the sample (ED50) and dorsal root ganglion (DRG) protein modulation of a peripheral direct adenosine monophosphate kinase alpha (AMPKα) activator (O304) in a murine model of lumbar disk puncture.
Learn More >Neuroinflammation and cytokines play critical roles in neuropathic pain and axon degeneration/regeneration. Cytokines of transforming growth factor-β superfamily have implications in pain and injured nerve repair processing. However, the transcriptional profiles of the transforming growth factor-β superfamily members in dorsal root ganglia under neuropathic pain and axon degeneration/regeneration conditions remain elusive.
Learn More >High impact chronic pain (HICP) characterizes the presence of a severe and troubling pain-related condition. To date, the prevalence of HICP in lumbar-spine surgery recipients and their HICP transition from pre-surgery is unexplored. The purpose was to define HICP prevalence, transition, and outcomes in lumbar spine surgery recipients and identify predictors of these HICP transition groups.
Learn More >Chronic low-back pain (CLBP) is a common disease with several negative consequences on the quality of life, work and activity ability and increased costs to the health-care system. When pharmacological, psychological, physical and occupational therapies or surgery fail to reduce CLBP, patients may be a candidate for Spinal Cord Stimulation (SCS). SCS consists of the transcutaneous or surgical implantation of different types of electrodes in the epidural space; electrodes are then connected to an Implanted Pulse Generator (IPG) that generates stimulating currents. Through spinal and supraspinal mechanisms based on the "gate control theory for pain transmission", SCS reduces symptoms of CLBP in the almost totality of well-selected patients and its effect lasts up to eight years in around 75% of patients. However, the evidence in favor of SCS still remains weak, mainly due to poor trial methodology and design. This narrative review is mainly addressed to those professionals that may encounter patients with CLBP failing conventional treatments. For this reason, we report the mechanisms of pain relief during SCS, the technical features and some clinical considerations about the application of SCS in patients with CLBP.
Learn More >The objective is to examine issues around treating infertility in patients with migraine.
Learn More >