Pain
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Patients with complex regional pain syndrome (CRPS) often show distinct neurocognitive dysfunctions, which were initially termed "neglect-like symptoms." So far, particularly the patients' feelings about the affected extremity, motor, and sensory aspects of the "neglect-like symptoms" have been investigated, possibly pointing to a disturbed body schema. Because patients with classical neurological neglect show diminished awareness regarding the perception of their body, as well as of the space around them, our hypothesis was that CRPS patients exhibit some signs of personal neglect and extrapersonal visuospatial problems over and beyond those seen in patients simply suffering from limb pain. We used quantitative sensory testing and motor assessment aimed at detecting motor and sensory loss, a standardized questionnaire calculating a neglect score, and applied a detailed neuropsychological test battery assessing different parietal lobe functions, including visual neglect. ⋯ Results show significant higher neglect scores for CRPS patients and the pain control group, but interestingly, CRPS patients and pain patients were indistinguishable. The results of the neuropsychological test battery did not demonstrate systematic variances, which would be indicative of a classical neurological neglect in CRPS patients, even though there were 3 CRPS patients who differed ≥ 2 SD from the mean of our healthy control group, with poorer results in ≥ 3 different tests. We assume that the "neglect-like syndrome" in most CRPS patients is different from typical neglect.
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The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. ⋯ Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development.