Evaluation of Using the Sphygmomanometer Test to Assess Pain Sensitivity in Chronic Pain Patients vs Normal Controls.

OBJECTIVES: Objectively measuring pain sensitivity has not been easy in primary care clinics. A sphygmomanometer test (a sensory test that measures an individual's nociceptive response to pressure using a standard blood pressure cuff) has recently been established to test pain sensitivity. Here, we examined the feasibility of using the sphygmomanometer test with chronic pain patients. DESIGN: Population, observational study. SETTINGS: A community hospital multidisciplinary Pain Center and a private nonprofit university. SUBJECTS: Healthy controls and chronic pain patients were recruited. METHODS: All subjects underwent four pain sensitivity tests: a pressure algometer test, a cold pressure test, a heat sensitivity test, and a sphygmomanometer test. Participants then completed four established surveys for evaluating depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (Fatigue Severity Scale), and pain catastrophizing (Pain Catastrophizing Scale). RESULTS: Although pain patients had significantly higher levels of depression, anxiety, fatigue, and pain catastrophizing, as well as reported pain scores, no significant differences in pain sensitivity were detected via any of the pain sensitivity tests. In the control but not the patient group, results from all pain sensitivity tests including the sphygmomanometer test were significantly correlated with each other. Unlike other pain sensitivity tests, the sphygmomanometer test did not correlate with measures of depression, anxiety, fatigue, or pain catastrophizing characteristics. CONCLUSIONS: Our results indicate the unique characteristics of the sphygmomanometer test as a pain sensitivity test, particularly when utilized for individuals with chronic pain. Multiple pain sensitivity tests that assess various sensory modalities are needed to evaluate pain sensitivities in chronic pain patients.

Polarizable simulations with second order interaction model (POSSIM) force field: developing parameters for protein side-chain analogues.

A previously introduced polarizable simulations with second-order interaction model (POSSIM) force field has been extended to include parameters for small molecules serving as models for peptide and protein side-chains. Parameters have been fitted to permit reproducing many-body energies, gas-phase dimerization energies, and geometries and liquid-phase heats of vaporization and densities. Quantum mechanical and experimental data have been used as the target for the fitting. The POSSIM framework combines accuracy of a polarizable force field and computational efficiency of the second-order approximation of the full-scale induced point dipole polarization formalism. The resulting parameters can be used for simulations of the parameterized molecules themselves or their analogues. In addition to this, these force field parameters are currently being used in further development of the POSSIM fast polarizable force field for proteins.

POSSIM: Parameterizing Complete Second-Order Polarizable Force Field for Proteins.

Previously, we reported development of a fast polarizable force field and software named POSSIM (POlarizable Simulations with Second order Interaction Model). The second-order approximation permits the speed up of the polarizable component of the calculations by ca. an order of magnitude. We have now expanded the POSSIM framework to include a complete polarizable force field for proteins. Most of the parameter fitting was done to high-level quantum mechanical data. Conformational geometries and energies for dipeptides have been reproduced within average errors of ca. 0.5 kcal/mol for energies of the conformers (for the electrostatically neutral residues) and 9.7° for key dihedral angles. We have also validated this force field by running Monte Carlo simulations of collagen-like proteins in water. The resulting geometries were within 0.94 Å root-mean-square deviation (RMSD) from the experimental data. We have performed additional validation by studying conformational properties of three oligopeptides relevant in the context of N-glycoprotein secondary structure. These systems have been previously studied with combined experimental and computational methods, and both POSSIM and benchmark OPLS-AA simulations that we carried out produced geometries within ca. 0.9 Å RMSD of the literature structures. Thus, the performance of POSSIM in reproducing the structures is comparable with that of the widely used OPLS-AA force field. Furthermore, our fitting of the force field parameters for peptides and proteins has been streamlined compared with the previous generation of the complete polarizable force field and relied more on transferability of parameters for nonbonded interactions (including the electrostatic component). The resulting deviations from the quantum mechanical data are similar to those achieved with the previous generation; thus, the technique is robust, and the parameters are transferable. At the same time, the number of parameters used in this work was noticeably smaller than that of the previous generation of our complete polarizable force field for proteins; thus, the transferability of this set can be expected to be greater, and the danger of force field fitting artifacts is lower. Therefore, we believe that this force field can be successfully applied in a wide variety of applications to proteins and protein-ligand complexes.