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Cervical nerve root injury induces a host of inflammatory mediators in the spinal cord that initiate and maintain neuronal hyperexcitability and pain. Secretory phospholipase A2 (sPLA2) is an enzyme that has been implicated as a mediator of pain onset and maintenance in inflammation and neural injury. Although sPLA2 modulates nociception and excitatory neuronal signaling in vitro, its effects on neuronal activity and central sensitization early after painful nerve root injury are unknown. This study investigated whether inhibiting spinal sPLA2 at the time of nerve root compression (NRC) modulates the pain, dorsal horn hyperexcitability, and spinal genes involved in glutamate signaling, nociception, and inflammation that are seen early after injury. Rats underwent a painful C7 NRC injury with immediate intrathecal administration of the sPLA2 inhibitor thioetheramide-phosphorlycholine. Additional groups underwent either injury alone or sham surgery. One day after injury, behavioral sensitivity, spinal neuronal excitability, and spinal cord gene expression for glutamate receptors (mGluR5 and NR1) and transporters (GLT1 and EAAC1), the neuropeptide substance P, and pro-inflammatory cytokines (TNFα, IL1α, and IL1β) were assessed. Treatment with the sPLA2 inhibitor prevented mechanical allodynia, attenuated neuronal hyperexcitability in the spinal dorsal horn, restored the proportion of spinal neurons classified as wide dynamic range, and reduced genes for mGluR5, substance P, IL1α, and IL1β to sham levels. These findings indicate spinal regulation of central sensitization after painful neuropathy and suggest that spinal sPLA2 is implicated in those early spinal mechanisms of neuronal excitability, perhaps via glutamate signaling, neurotransmitters, or inflammatory cascades.
Learn More >Assess the burden and co-occurrence of pain, depression, and posttraumatic stress disorder (PTSD) among service members who sustained a major limb injury, and examine whether these conditions are associated with functional outcomes.
Learn More >Chronic pain from temporomandibular disorders remains an undertreated condition with debate regarding the most effective treatment modalities.
Learn More >Nonspecific neck pain is associated with chronic pain, disability, reduced cervical mobility, postural control disorders and impaired proprioceptive control.
Learn More >Chemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of cyclic AMP response element-binding protein (CREB) in dorsal root ganglion (DRG) neurons. Blocking this increase through DRG microinjection of Creb siRNA attenuated paclitaxel-induced mechanical, heat, and cold nociceptive hypersensitivities. Mimicking this increase through DRG microinjection of the adeno-associated virus 5 expressing full-length Creb mRNA led to enhanced responses to basal mechanical, heat, and cold stimuli in mice in absence of paclitaxel treatment. Mechanically, paclitaxel-induced increase of DRG CREB protein augmented Dnmt3a promoter activity and participated in the paclitaxel-induced upregulation of DNMT3a protein in the DRG. CREB overexpression also elevated the expression of DNMT3a in in vivo and in vitro DRG neurons of naïve mice. Given that DNMT3a is an endogenous instigator of CIPNP and that CREB co-expresses with DNMT3a in DRG neurons, CREB may be a key player in CIPNP through transcriptional activation of the Dnmt3a gene in primary sensory neurons. CREB is thus a likely potential target for the therapeutic management of this disorder.
Learn More >Fibromyalgia (FM) is a highly disabling condition characterized by widespread chronic pain. Physical exercise, such as walking, has been recommended as the treatment of choice for FM. However, adherence to physical exercise tends to be poor. Pain is one of the main inhibitors to adhere to walking in FM patients. The main objective of this study has been to determine whether there is a clinical and psychosocial profile to help predict individual differences in adherence to walking in a sample of patients with FM with severe pain levels. In this cross-sectional study, the sample was composed of 172 women with FM and severe pain levels (> 7 in an 11-point numerical scale). Women were classified into two groups: (1) those who walked regularly and (2) patients who rarely or never walked. Group differences regarding clinical outcomes (e.g., FM impact, anxiety, depression, cognitive fusion, catastrophizing, affect, and personality), sociodemographic variables, and medical history were analyzed. Patients who walked despite pain significantly reported less impact of FM, anxiety, depression, catastrophizing, cognitive fusion, negative affect, openness to experience, agreeableness, and conscientiousness. The unique predictors of group membership (walking versus no walking) in a binary regression were FM impact and negative affect. The results show that adherence to exercise might be influenced and predicted by the clinical profile of the patient, which suggests that personalized motivational interventions should be addressed to this at-risk subgroup.
Learn More >To define the melanopsin and cone luminance retinogeniculate pathway contributions to photophobia in healthy controls and migraineurs.
Learn More >Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.
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