Brain activity in an animal model of paclitaxel- induced neuropathic pain

Trabajo presentado en el 37th Annual Meeting; European Society for Magnetic Resonance In Medicine and Biology (ESMRMB), celebrado en Rotterdam (Países Bajos) del 3 al 5 de octubre de 2019.[Purpose/Introduction]: Paclitaxel (PTX) is widely used for cancer treatment but also causes numerous deleterious effects. Chemotherapy-induced neuropathy (CIN) is one of the most common complications and neuropathic pain arises frequently as drawback [1]. The mechanisms underlying pain during CIN are starting to be uncovered namely the alterations at the peripheral nervous system [2]. However, the effects of cytostatic at the central nervous system remain poorly understood. This experimental work aimed to evaluate the effects of PTX on neuronal activation in brain areas involved in pain modulation using functional magnetic resonance imaging (fMRI) approaches. Subjects and Methods: Wistar rats were intraperitoneally injected in 4 alternate days with PTX (2 mg/ml), 4% dimethyl sulfoxide (DMSO)(vehicle) or saline. Imaging studies were performed at 0 (T0), 28 (T28) and 56 days (T56) after CIN induction in a 7T MRI system. Rats were anaesthetized with isoflurane (1–1.5%, 1L/min O 2). Before scanning, mechanical nociceptive stimulation was applied to the hindpaw. Diffusion images were acquired in 3 directions with 9b values (0–1800 s/mm 2) and TR/TE =3000/31 ms, 4-s EPI readouts, D / d = 20/4 ms, 0.164 mm 2/pixel, slice-thickness 1.5 mm, axial orientation. Magnetization transfer (MT) images were acquired with TR/TE = 2500/10 ms and MT train: 50 pulses, 5.5 lT, 5 ms, offset 1500 Hz. Images were computed with homemade program software to yield parametric maps, and ROIs were manually selected. Rats were sacrificed at T56 with a focused high-power microwave (5000 W). 1 H HR-MAS spectra of dissected brain regions were acquired in a 11.7T with a CPMG sequence and processed with LCModel. [Results]: PTX treatment induced a significantly decrease of MT ratio (MTR) percentage at T28 compared with T0 in PAG and hypothalamus (Fig. 1). A significant increase of apparent diffusion coefficient (ADC) values was observed in periaqueductal gray (PAG) at T28 and T56 in PTX group compared with vehicle group. However, the thalamus and hypothalamus showed a decrease of ADC values over time (Fig. 2). A higher statistic difference on Fast Diffusion Coefficient (FDC) values in hypothalamus and thalamus was observed at T56 between saline and PTX groups. The PAG showed a Slow Diffusion Phase (SDP) significantly higher in PTX group at T56 compared with T0. In hypothalamus, a significant decrease of SDP was detected in PTX group at T56 compared with saline group and paclitaxel treatment at T28 (Fig. 3). Some detected metabolites in thalamus and hypothalamus, namely taurine, changed throughout of three experimental groups