Articles: neuropathic-pain.
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The concept "nociplastic pain" has been developed for patients with features of nociceptive system sensitization that are not explained as nociceptive or neuropathic. Here, we tested how well the recently published grading system differentiates between chronic primary and secondary pain conditions. We recruited patients with fibromyalgia (FMS, n = 41), complex regional pain syndrome (CRPS, n = 11), osteoarthritis (OA, n = 21), or peripheral nerve injury (PNI, n = 8). ⋯ Based on these data, specificity remained excellent (93%), but sensitivity dropped substantially (60%) due to lacking evidence for pain hypersensitivity in many patients with FMS. This low sensitivity suggests that the published grading system is not suitable for screening purposes. We suggest structural and content modifications to improve sensitivity, including placement of patient history before clinical examination and addition of a high tender point count as evidence for widespread pain hypersensitivity.
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Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. ⋯ We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.
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The pain experience of patients with sickle cell disease (SCD) frequently consists of episodes of acute exacerbation. However, recent studies suggest that many patients who suffer from SCD have symptoms of chronic neuropathic pain. Additional research is needed to determine what role genotype plays in the patient's pain phenotype experience in SCD. The purpose of our project was to determine whether a catechol-O-methyltransferase (COMT) single nucleotide polymorphism (SNP), rs4680, was associated with the experience of chronic neuropathic pain in patients with SCD. ⋯ Further studies with larger samples are needed to determine if the Met/Met genotype predisposes patients with SCD to neuropathic pain and if other polymorphisms in the COMT gene play a role in this process.
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Transient receptor potential ankyrin 1 (TRPA1) is implicated in physiological and pathological nociceptive signaling, but the clinical benefit of TRPA1 antagonists in chronic pain is not clearly demonstrated. LY3526318 is an oral, potent, and selective novel TRPA1 antagonist. The Chronic Pain Master Protocol was used to evaluate the safety and efficacy of LY3526318 in 3 randomized, placebo-controlled, proof-of-concept studies in knee osteoarthritis pain (OA), chronic low back pain (CLBP), and diabetic peripheral neuropathic pain (DPNP). ⋯ LY3526318 showed a potential drug-induced hepatotoxic effect posing a risk for clinical development. No other safety signals were identified. LY3526318 showed potential for different responses among chronic pain indications and patient subpopulations, highlighting challenges in developing TRPA1 antagonists but supporting their value as a target in managing chronic pain.
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Dysfunctional hyperactivity of the lateral habenula nucleus (LHb) has emerged as a critical marker for pain-related mood impairments. Acting as a central hub, the LHb filters and disseminates pertinent information to other brain structures during learning. However, it is not well understood how intra-LHb activity is altered during cognitive demand under neuropathic pain conditions. ⋯ Our results showed that the induction of neuropathic pain disrupted WM encoding accuracy and intra-LHb functional neuronal connectivity. This disruption was reversed by optogenetic inhibition of LHb CaMKIIα-expressing neurons, which also produced antinociceptive effects. Together, our findings provide insight into how intra-LHb networks reorganize information to support different task contexts, suggesting that the abnormal pain-related intra-LHb dynamic segregation of information may contribute to poor cognitive accuracy in male rodents during pain experiences.