Pain
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Children with Christianson syndrome (CS), an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the alkali cation/proton exchanger SLC9A6/NHE6, display severe cognitive impairments, mutism, and sensory abnormalities such as hyposensitivity to pain. However, it is unclear whether these children display other sensory abnormalities and whether their pain hyposensitivity is the result of an elevated pain threshold or a complete insensitivity to pain. To better characterize the sensory abnormalities in this disorder, we used a combination of a mouse model of CS and pain questionnaires directed at nonverbal patients with CS. ⋯ Surprisingly, CS mice also displayed aversive reactions to innocuous stimuli, which prompted us to examine whether such reactions were also present in children with CS. Indeed, the results from the PSQ revealed that 30% to 50% of these patients showed an aversive response to normally innocuous stimuli like light touch and gusts of air. Our results demonstrate that children with CS have aversive reactions to innocuous stimuli and are hyposensitive to painful stimuli, the latter making them at risk for developing complications from unreported injuries.
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The objective of this study was to assess the frequency of IgG autoantibodies in patients with fibromyalgia syndrome (FMS), to characterize their binding to dorsal root ganglion (DRG) neurons and glial cells, and to assess whether specific DRG binding patterns correlate with clinical symptoms. Sera of a cohort of 184 patients with FMS and 55 control sera were used to test binding of patient IgG on rat DRG sections. ELISA, Western blot, and preadsorption tests were used to search for potential target antigens. ⋯ Current pain intensity correlated positively with IgG binding to FABP7 immunoreactive structures, and burning pain was associated with binding to transient receptor potential vanilloid 1 immunoreactive neurons. Specific antibody detection revealed 13 of 68 sera positive for anti-citrullinated peptide antibodies, 9 of 68 positive for SOX1 antibodies, 7 of 68 positive for antibodies against the serotonin receptor 5HT1AR, and 3 of 68 positive for fibroblast growth factor 3 antibodies. Our findings support the notion of an immune activation in a subgroup of patients with FMS.
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Spine-related neck-arm pain is heterogeneous and may present on a spectrum between nociceptive and neuropathic pain. A recently developed mechanism-based clinical framework for spine-related pain distinguishes between spinally referred pain without neurological deficits (somatic referred pain, heightened nerve mechanosensitivity, radicular pain), with neurological deficits (radiculopathy), and mixed-pain presentations. This study investigated differences in somatosensory and clinical profiles of patients with unilateral spine-related neck-arm pain grouped according to the clinical framework. ⋯ Symptom descriptors, such as burning (P < 0.031), tingling (P < 0.018), pins and needles (P < 0.031), numbness (P < 0.016), spontaneous pain (P < 0.001), and electric pain/shock (P < 0.026) were more common in the radicular/radiculopathy groups compared with the somatic/mechanosensitivity groups. There were no differences in psychosocial parameters between the groups. The phenotypic profiles support the construct of the clinical examination and patient classification and its application in clinical practice according to a clinical framework for spine-related pain.
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Neuropathic pain (NP) is a chronic condition caused by nerve injuries, such as nerve compression. Understanding its underlying neurobiological mechanisms is critical for developing effective treatments. Previous studies have shown that Kinesin family member 1A (Kif1a) heterozygous deficient mice display sensory deficits in response to nociceptive stimuli. ⋯ Furthermore, TET1 knockdown or overexpression significantly affected pain-related behaviors, as well as Kif1a methylation and transcription. Female mice given intrathecal injections of PI3K inhibitors exhibited similar molecular and behavioral outcomes as male mice. These findings offer new insights into NP mechanisms, suggesting that targeting the PI3K/KIF1A axis could be a promising therapeutic approach for NP treatment.