Pain
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Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50±9.0 years; disease duration: 12 weeks [IQR 8-24]), 10 controls (6 women; mean age 58±9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43±15 years; time after fracture: 15 weeks [IQR: 6-22]). ⋯ The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.
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There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry, and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. ⋯ More specifically, the presence of neuropathic pain after spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content, and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain.
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Mirror-image pain is characterized by mechanical hypersensitivity on the uninjured mirror-image side. Recent reports favor central mechanisms, but whether peripheral mechanisms are involved remains unclear. We used unilateral spinal nerve ligation (SNL) to induce mirror-image pain in rats. ⋯ In the contralateral DRG, the SNL-evoked tumor necrosis factor alpha (TNF-α) increase, which started later than in the ipsilateral DRG and cerebrospinal fluid, occurred earlier than satellite glial activation and the NGF increase. Intrathecal injection of TNF-α into naive rats not only activated satellite glia to produce extra NGF in the DRG but also evoked mechanical hypersensitivity, which could be attenuated by anti-NGF injection. These results suggest that after SNL, satellite glia in the contralateral DRG are activated by TNF-α that diffuses from the injured side via cerebrospinal fluid, which then activates satellite glia to produce extra NGF to enhance nociceptor excitability, which induces mirror-image pain.
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Comparative Study
Heritability of Nociception IV: Neuropathic pain assays are genetically distinct across methods of peripheral nerve injury.
Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified 5 genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional 9 assays of nociception and hypersensitivity, with the following goals: to replicate the previously identified 5 pain types; to test whether any of the newly added pain assays represent novel genetically distinct pain types; and to test the level of genetic relatedness among 9 commonly used neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the 2 previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. ⋯ In addition, 2 itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types.
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Pain is commonly assessed by subjective reports on rating scales. However, in many experimental and clinical settings, an additional, objective indicator of pain is desirable. In order to identify an objective, parametric signature of pain intensity that is predictive at the individual stimulus level across subjects, we recorded skin conductance and pupil diameter responses to heat pain stimuli of different durations and temperatures in 34 healthy subjects. ⋯ These results indicate that perceived pain is best reflected by the temporal dynamics of autonomic responses. Application of the regression model to an independent data set of 20 subjects resulted in a very good prediction of the pain ratings demonstrating the generalizability of the identified temporal pattern. Utilizing the readily available temporal information from skin conductance and pupil diameter responses thus allows parametric prediction of pain in human subjects.