Involvement of NIPSNAP1, a neuropeptide nocistatin-interacting protein, in inflammatory pain.

BACKGROUND: Chronic pain associated with inflammation is an important clinical problem, and the underlying mechanisms remain poorly understood. 4-Nitrophenylphosphatase domain and nonneuronal SNAP25-like protein homolog (NIPSNAP) 1, an interacting protein with neuropeptide nocistatin, is implicated in the inhibition of tactile pain allodynia. Although nocistatin inhibits some inflammatory pain responses, whether NIPSNAP1 affects inflammatory pain appears to be unclear. Here, we examined the nociceptive behavioral response of NIPSNAP1-deficient mice and the expression of NIPSNAP1 following peripheral inflammation to determine the contribution of NIPSNAP1 to inflammatory pain. RESULTS: Nociceptive behavioral response increased in phase II of the formalin test, particularly during the later stage (26-50 min) in NIPSNAP1-deficient mice, although the response during phase I (0-15 min) was not significantly different between the deficient and wild-type mice. Moreover, phosphorylation of extracellular signal-related kinase was enhanced in the spinal dorsal horn of the deficient mice. The prolonged inflammatory pain induced by carrageenan and complete Freund's adjuvant was exacerbated in NIPSNAP1-deficient mice. NIPSNAP1 mRNA was expressed in small- and medium-sized neurons of the dorsal root ganglion and motor neurons of the spinal cord. In the formalin test, NIPSNAP1 mRNA was slightly increased in dorsal root ganglion but not in the spinal cord. In contrast, NIPSNAP1 mRNA levels in dorsal root ganglion were significantly decreased during 24-48 h after carrageenan injection. Prostaglandin E2, a major mediator of inflammation, stimulated NIPSNAP1 mRNA expression via the cAMP-protein kinase A signaling pathway in isolated dorsal root ganglion cells. CONCLUSIONS: These results suggest that changes in NIPSNAP1 expression may contribute to the pathogenesis of inflammatory pain.

Bilateral facial nerve palsy due to otitis media associated with myeloperoxidase-antineutrophil cytoplasmic antibody.

Otitis media (OM) is well known as a common feature of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA)-related Wegener granulomatosis, but is a very rare condition in myeloperoxidase ANCA (MPO-ANCA)-related vasculitis. In addition, there have been a few reports showing an association of MPO-ANCA-positive OM with cranial polyneuropathy. In this report, we describe 2 patients with bilateral facial nerve palsy due to MPO-ANCA-related OM. One patient also had bilateral trigeminal neuropathy, pachymeningitis and MPO-ANCA-related glomerulonephritis, whereas the other showed isolated bilateral facial nerve palsy with OM. In both the patients, treatment with prednisolone and immune-suppressant drugs resulted in an improvement of OM and cranial polyneuropathy. Physicians should be aware that MPO-ANCA-positive OM can cause bilateral facial nerve palsy.

Multi-shelled q-ball imaging: moment-based orientation distribution function.

PURPOSE: q-ball imaging (QBI) reconstructs the orientation distribution function (ODF) that describes the probability for a spin to diffuse in a given direction, and it is capable of identifying intravoxel multiple fiber orientations. The local maxima of ODF are assumed to indicate fiber orientations, but there is a mismatch between the orientation of a fiber crossing and the local maxima. We propose a novel method, multi-shelled QBI (MS-QBI), that gives a new ODF based on the moment of the probability density function of diffusion displacement. We test the accuracy of the fiber orientation indicated by the new ODF and test fiber tracking using the new ODF. METHODS: We performed tests using numerical simulation. To test the accuracy of fiber orientation, we assumed that 2 fibers cross and evaluated the deviation of the measured crossing angle from the actual angle. To test the fiber tracking, we used a numerical phantom of the cerebral hemisphere containing the corpus callosum, projection fibers, and superior longitudinal fasciculus. In the tests, we compared the results between MS-QBI and conventional QBI under the condition of approximately equal total numbers of diffusion signal samplings between the 2 methods and chose the interpolation parameter such that the stabilities of the results of the angular deviation for the 2 methods were the same. RESULTS: The absolute value of the mean angular deviation was smaller in MS-QBI than in conventional QBI. Using the moment-based ODF improved the accuracy of fiber pathways in fiber tracking but maintained the stability of the results. CONCLUSION: MS-QBI can more accurately identify intravoxel multiple fiber orientations than can QBI, without increasing sampling number. The high accuracy of MS-QBI will contribute to the improved tractography.