Articles: chronic.
-
Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central sensitization and chronic pain. However, NMDAR antagonists display limited therapeutic potential because of their adverse side effects. Novel approaches targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of NMDARs show efficacy in preclinical pain models. ⋯ Finally, TAT-GESV (i.t.) did not induce NMDAR-mediated motor ataxia in the rotarod test and did not alter basal nociceptive thresholds in the radiant heat tail-flick test. These observations support the hypothesis that antiallodynic efficacy of an nNOS-NOS1AP disruptor may result, at least in part, from blockade of p38 MAPK-mediated downstream effects. Our studies demonstrate, for the first time, that disrupting nNOS-NOS1AP protein-protein interactions attenuates mechanistically distinct forms of neuropathic pain without unwanted motor ataxic effects of NMDAR antagonists.
-
Anesthesia and analgesia · May 2018
ReviewPredicting Severity of Acute Pain After Cesarean Delivery: A Narrative Review.
Cesarean delivery is one of the most common surgical procedures in the United States, with over 1.3 million performed annually. One-fifth of women who undergo cesarean delivery will experience severe pain in the acute postoperative period, increasing their risk of developing chronic pain and postpartum depression, and negatively impacting breastfeeding and newborn care. A growing body of research has investigated tools to predict which patients will experience more severe pain and have increased analgesic consumption after cesarean delivery. ⋯ Thirteen articles were included in the final review: 5 utilizing quantitative sensory testing, including patient responses to pressure, electrical, and thermal stimuli; 1 utilizing hyperalgesia testing; 1 using response to local anesthetic wound infiltration; 4 utilizing preoperative psychometric evaluations including the State-Trait Anxiety Inventory, the Pain Catastrophizing Scale, the Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and simple questionnaires; and 2 utilizing a combination of quantitative sensory tests and psychometric evaluations. A number of modalities demonstrated statistically significant correlations with pain outcomes after cesarean delivery, but most correlations were weak to modest, and many modalities might not be clinically feasible. Response to local anesthetic infiltration and a tool using 3 simple questions enquiring about anxiety and anticipated pain and analgesic needs show potential for clinical use, but further studies are needed to evaluate the utility of these predictive tests in clinical practice.
-
Neuropathic pain (NP) is an increasingly common chronic pain state and a major health burden, affecting approximately 7% to 10% of the general population. Emerging evidence suggests that genetic factors could partially explain individual susceptibility to NP and the estimated heritability in twins is 37%. The aim of this study was to systematically review and summarize the studies in humans that have investigated the influence of genetic factors associated with NP. ⋯ These findings demonstrate an important and specific contribution of genetic factors to the risk of developing NP. However, large-scale replication studies are required to validate these candidate genes. Our review also highlights the need for genome-wide association studies with consistent case definition to elucidate the genetic architecture underpinning NP.
-
Numerous preclinical studies support the role of spinal neuroimmune activation in the pathogenesis of chronic pain, and targeting glia (eg, microglia/astrocyte)- or macrophage-mediated neuroinflammatory responses effectively prevents or reverses the establishment of persistent nocifensive behaviors in laboratory animals. However, thus far, the translation of those findings into novel treatments for clinical use has been hindered by the scarcity of data supporting the role of neuroinflammation in human pain. ⋯ Furthermore, the neuroforaminal translocator protein signal was associated with responses to fluoroscopy-guided epidural steroid injections, supporting its role as an imaging marker of neuroinflammation, and highlighting the clinical significance of these observations. These results implicate immunoactivation at multiple levels of the nervous system as a potentially important and clinically relevant mechanism in human radicular pain, and suggest that therapies targeting immune cell activation may be beneficial for chronic pain patients.