Neuropathic pain is a chronic condition that remains a major clinical problem owing to high resistance to available therapy. Recent studies have indicated that chemokine signaling pathways are crucial in the development of painful neuropathy; however, the involvement of CC chemokine receptor 4 (CCR4) has not been fully elucidated thus far. Therefore, the aim of our research was to investigate the role of CCR4 in the development of tactile and thermal hypersensitivity, the effectiveness of morphine/buprenorphine, and opioid-induced tolerance in mice exposed to chronic constriction injury (CCI) of the sciatic nerve. The results of our research demonstrated that a single intrathecal or intraperitoneal administration of C021, a CCR4 antagonist, dose dependently diminished neuropathic pain-related behaviors in CCI-exposed mice. After sciatic nerve injury, the spinal expression of
CCL17
and
CCL22
remained unchanged in contrast to that of
CCL2
, which was significantly upregulated until day 14 after CCI. Importantly, our results provide evidence that in naive mice, CCL2 may evoke pain-related behaviors through CCR4 because its pronociceptive effects are diminished by C021. In CCI-exposed mice, the pharmacological blockade of CCR4 enhanced the analgesic properties of morphine/buprenorphine and delayed the development of morphine-induced tolerance, which was associated with the silencing of IBA-1 activation in cells and decrease in CCL2 production. The obtained data suggest that the pharmacological blockade of CCR4 may be a new potential therapeutic target for neuropathic pain polytherapy.
Purpose The Core Outcome Measures Index (COMI) is a short, multidimensional outcome scale validated for the use by patients with spinal disorders. It is a recommended instrument in the Spine Society of Europe Spine Tango Registry. The purpose of this study was to produce a crossculturally adapted and validated Polish COMI. Methods The cross-cultural adaptation was carried out using the established guidelines. One-hundred and sixtynine patients with chronic low back pain were enrolled, 89 took part in the reproducibility part of the study.Data quality, construct validity and reproducibility were assessed. Results The quality of data was very good with very few missing answers and modest floor effect. Reliability expressed as intraclass correlation coefficient (ICC) was 0.90 (95 % CI 0.85-0.93) for the overall COMI score and for most of the individual core items. The minimum detectable change (MDC 95% ) was 1.79. Conclusions The Polish version of COMI showed a favorable reproducibility similar to that of previously tested language versions. The COMI scores correlated sufficiently with existing measures. This version of the COMI is a valuable instrument for the use by Polishspeaking patients with spinal disorders.Electronic supplementary material The online version of this article
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