Prism adaptation to optical deviation alleviates pathologic pain.

BACKGROUND: The human visual and somatosensory systems are interdependent. Using a visual subjective body-midline (SM) judgment task, we previously confirmed that pathologic pain and deafferentation can modify visuospatial perception, indicating that altered somatosensory experience can modify visual perception. Conversely, in the present study we investigated whether a change in visual experience can modify perception of pathologic pain. METHODS: We used prism adaptation (PA) to modify subjects' visual experience. Five patients with complex regional pain syndrome (CRPS) adapted to wedge prisms, producing a 20-degree visual displacement toward the unaffected side. Further, we used several types of prisms in a longitudinal single-case study. Wearing prismatic goggles, the subjects performed a target-pointing task once a day for 2 weeks. We evaluated pain intensity and visual SM judgment to measure the adaptive aftereffects at three time points: before PA (pre-test), immediately after the first PA exposure (IA-test), and after a 14-day sequence of PA exposure (post-test). RESULTS: PA toward the unaffected side alleviated pathologic pain and other CRPS pathologic features, when measured at post-test. None of the IA-test results showed an analgesic effect. In the longitudinal study, sham PA and 5-degree PA did not produce any effects, and PA toward the affected side actually exacerbated the subjective pain. CONCLUSIONS: Our findings suggest that vision can influence pathologic pain, and preliminarily suggest that prism adaptation has a direction-specific and reproducible effect on not only pathologic pain but also other CRPS pathologic features. Thus, prism adaptation may be a viable cognitive treatment for CRPS.

Pathologic pain distorts visuospatial perception.

Spatial perception is achieved by integrating multisensory information. Using visual subjective body midline (vSM) judgments in patients with unilateral limb pain (complex regional pain syndrome [CRPS]), we found that their vSM deviated toward the affected side; however, deafferentation of the affected limb caused a transient pain decrease and a transient shift of the vSM deviation toward the unaffected side. Our results indicate that the persistent pain state in CRPS distorts visuospatial perception.

NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model.

Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-kappaB), plays a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-kappaB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-kappaB decoy, we tested whether the activated NF-kappaB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections of NF-kappaB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-kappaB, is involved in the pathogenesis of neuropathic pain.

IL-15 and IL-15 receptor selectively regulate differentiation of common mucosal immune system-independent B-1 cells for IgA responses.

We show in this report a new regulatory role for IL-15 and IL-15R in the development of B-1 cells and their differentiation into IgA-producing cells. Mucosal IgA levels were found to be inhibited by anti-IL-15 mAb treatment in vivo, but enhanced by administration of rIL-15, while serum IgA levels remained unaffected. Mucosal B-1 cells preferentially proliferated in response to IL-15 in vitro. When mucosal B-1 and B-2 cells were separated into surface (s)IgM(+)sIgA(-) and sIgM(-)sIgA(+) fractions, IL-15R-specific mRNA was found to be predominant in both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-1 cells at a much higher level than B-2 cells. Further, incubation of these different subsets of B-1 and B-2 cells with IL-15 resulted in greater enhancement of the corresponding receptor expression by B-1 subset when compared with B-2 fraction. Interestingly, de novo isolated sIgM(+)sIgA(-) B-1, but not sIgM(+)sIgA(-) B-2, cells were already class-switched cells because the germline Calpha transcript was detected and was then further enhanced by IL-15. IL-15 also supported differentiation of both sIgM(+)sIgA(-) and sIgM(-)sIgA(+) B-1 cells into IgA-producing cells. Taken together, these findings suggest that IL-15 is a critically important cytokine for the differentiation of both sIgM(+),IgA(-) and sIgM(-)sIgA(+) B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues.

The influence of surgical stress on T cells: enhancement of early phase lymphocyte activation.

UNLABELLED: For the control of postoperative infection, it may be important to understand the possible influences of surgical stress on the host immune system. To this end, we examined how the early phase of lymphocyte activation was affected in patients after major surgery (eight patients with esophageal carcinoma and six undergoing cardiac surgery) using a flow cytometric assay based on expression of the early activation antigen, CD69. Freshly isolated T cell in preoperative and postoperative samples did not express CD69. When peripheral blood mononuclear cells were stimulated in vitro, the expression of CD69 was greatly enhanced in both CD4 and CD8 T cells, compared with the preoperative samples. The proportion of de novo CD69-expressing cells in the CD4 subset was approximately 3 times (Postoperative Day 1) and 4 times (Postoperative Days 2, 3, 5, and 7) greater than those preoperatively, whereas the proportion of de novo CD69-expressing cells in the CD8 subset was approximately 1.5 times (Postoperative Days 2 and 5) and 2 times (Postoperative Day 3) greater than those preoperatively. The proportion of CD69+ cells was significantly greater in the CD4+ subset than in the CD8+ subset during the postoperative period. IMPLICATIONS: Our results show that major surgical stress enhances the early phase of lymphocyte activation. The augmentation of activation was greater in CD4 (helper) T cells than in CD8 (cytotoxic) T cells.