RESUMO
PURPOSE: We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na+-channel blockers (e.g., oxcarbazepine). METHODS: 104 patients with at least "probable" NP in the surgical area were included. All patients had been treated for breast cancer 4-9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. RESULTS: Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. CONCLUSIONS: Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na+-channel blockers.
Assuntos
Neoplasias da Mama/cirurgia , Hiperalgesia/diagnóstico , Hiperestesia/diagnóstico , Mastectomia/efeitos adversos , Neuralgia/diagnóstico , Dor Pós-Operatória/diagnóstico , Idoso , Estudos de Coortes , Feminino , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Hiperalgesia/fisiopatologia , Hiperestesia/tratamento farmacológico , Hiperestesia/etiologia , Hiperestesia/fisiopatologia , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Medição da Dor , Limiar da Dor/fisiologia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Sensação/fisiologia , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
The Ikaros family transcription factor Aiolos is important for B cell function, since B cells of Aiolos-null mutant mice exhibit an activated phenotype, enhanced B-cell receptor (BCR) signalling response and develop a systemic lupus erythematosus (SLE) type autoimmune disease. Aiolos has also been reported to interact with anti-apoptotic Bcl-2 and Bcl-x(L) in T cells, but whether Aiolos regulates cell death has not been studied in B cells. Here we show that the disruption of Aiolos in the DT40 B cell line induces a cell death sensitive phenotype, as the Aiolos(-/-) cells are more prone to apoptosis by nutritional stress, BCR cross-linking, UV- or gamma-irradiation. Furthermore, the Aiolos(-/-) cells have defective Ig gene conversion providing evidence that Aiolos is needed for the somatic diversification of the BCR repertoire. The re-expression of DNA-binding isoform Aio-1 was able to restore the gene conversion defect of the Aiolos-deficient cells, whereas the introduction of dominant negative isofom Aio-2 had no effect on gene conversion, thus demonstrating the functional importance of alternative splicing within Ikaros family. Although the Aiolos(-/-) cells exhibit reduced expression of activation-induced cytidine deaminase (AID), ectopic AID overexpression did not restore the gene conversion defect in the Aiolos(-/-) cells. Our findings indicate that Aiolos may regulate gene conversion in an AID independent manner.