Search Results (10)

Bone cancer and its related chronic pain are huge clinical problems since the available drugs are often ineffective or cannot be used long term due to a broad range of side effects. The mechanisms, mediators and targets need to be identified to determine potential novel therapies. Here, we characterize a mouse bone cancer model induced by intratibial injection of K7M2 osteosarcoma cells using an integrative approach and investigate the role of capsaicin-sensitive peptidergic sensory nerves. The mechanical pain threshold was assessed by dynamic plantar aesthesiometry, limb loading by dynamic weight bearing, spontaneous pain-related behaviors via observation, knee diameter with a digital caliper, and structural changes by micro-CT and glia cell activation by immunohistochemistry in BALB/c mice of both sexes. Capsaicin-sensitive peptidergic sensory neurons were defunctionalized by systemic pretreatment with a high dose of the transient receptor potential vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX). During the 14- and 28-day experiments, weight bearing on the affected limb and the paw mechanonociceptive thresholds significantly decreased, demonstrating secondary mechanical hyperalgesia. Signs of spontaneous pain and osteoplastic bone remodeling were detected both in male and female mice without any sex differences. Microglia activation was shown by the increased ionized calcium-binding adapter molecule 1 (Iba1) immunopositivity on day 14 and astrocyte activation by the enhanced glial fibrillary acidic protein (GFAP)-positive cell density on day 28 in the ipsilateral spinal dorsal horn. Interestingly, defunctionalization of the capsaicin-sensitive afferents representing approximately 2/3 of the nociceptive fibers did not alter any functional parameters. Here, we provide the first complex functional and morphological characterization of the K7M2 mouse osteosarcoma model. Bone-cancer-related chronic pain and hyperalgesia are likely to be mediated by central sensitization involving neuroinflammation via glial cell activation in the spinal dorsal horn, but not the capsaicin-sensitive sensory neuronal system. Full article

In our case, the malformation was diagnosed prenatally at 40 weeks of gestation, and at the age of 14 days, the malformation was removed combined with a segmentectomy of the sixth segment of the left lung. Preoperative diagnostics focus on 3D-CT reconstruction and detailing of the anatomical variations of all arterial and venous vessels, as evident from our case. Treatment includes surgical removal or a minimally invasive interventional approach through the embolization of the vessel afferent to the malformation. After the operation, the child was discharged on the 30th day after birth in good condition and is developing normally. Early operative intervention is of great importance for the favorable outcome of the condition. In our case, this was hypoxemia with a saturation of 70-75%. The rare and often missed prenatal diagnosis of fetal AV malformation is significant for the adequate postnatal treatment and development of affected children. Full article

This paper presents a literature review and a case of an 83-year-old otherwise healthy female patient with a history of recent syncope, a sudden-onset right-sided temporal headache, diplopia, and vision loss. An exam revealed right-sided upper eyelid ptosis, myosis, vision loss, ophthalmoplegia, and a positive relative afferent pupillary defect on the right eye. CT showed sphenoid sinus opacification, eroded lateral sinus wall, Vidian canal, disease extension to the posterior ethmoid air cells, orbital apex, medial orbital wall, and pterygopalatine fossa. An orbital apex syndrome (Jacod’s syndrome), Horner syndrome, and pterygopalatine fossa infection were diagnosed due to the acute invasive fungal sinusitis developed from a sphenoid sinus fungal ball. The patient was treated with antimicrobial therapy and transnasal endoscopic surgery twice to decompress the orbital apex, drain the abscess and obtain specimens for analysis. The right-sided ptosis, visual loss, ophthalmoplegia, and headache resolved entirely. No immune or comorbid diseases were identified, microbiological and histopathological analyses were negative, and MRI could not be performed on the presented patient. For that reason, the diagnostic procedure was non-standard. Nevertheless, the treatment outcome of this vision and life-threatening disease was satisfactory. Treating the fungal ball in an older or immunocompromised patient is essential to prevent invasive fungal rhinosinusitis and fatal complications. Full article

What is the significance of a touch encoded by slow-conducted unmyelinated C-tactile (CT) fibers? It is the so-called affiliative touch, which has a fundamental social impact. In humans, it has been demonstrated that the affiliative valence of this kind of touch is encoded by a dedicated central network, not involved in the encoding of discriminative touch, namely, the “social brain”. Moreover, CT-related touch has significant consequences on the human autonomic system, not present in the case of discriminative touch, which does not involve CT fibers as the modulation of vagal tone. In addition, CT-related touch provokes central effects as well. An interesting finding is that CT-related touch can elicit “mirror-like responses” since there is evidence that we would have the same perception of a caress regardless of whether it would be felt or seen and that the same brain areas would be activated. Information from CT afferents in the posterior insular cortex likely provides a basis for encoding observed caresses. We also explored the application of this kind of touch in unphysiological conditions and in premature newborns. In the present literature review, we aim to (1) examine the effects of CT-related touch at autonomic and central levels and (2) highlight CT-related touch and mirror networks, seeking to draw a line of connection between them. Finally, the review aims to give an overview of the involvement of the CT system in some neurologic and psychiatric diseases. Full article

Adaptation to external forces relies on a well-functioning proprioceptive system including muscle spindle afferents. Muscle length and tension control in reaction to external forces is most important regarding the Adaptive Force (AF). This study investigated the effect of different procedures, which are assumed to influence the function of muscle spindles, on the AF. Elbow flexors of 12 healthy participants (n = 19 limbs) were assessed by an objectified manual muscle test (MMT) with different procedures: regular MMT, MMT after precontraction (self-estimated 20% MVIC) in lengthened position with passive return to test position (CL), and MMT after CL with a second precontraction in test position (CL-CT). During regular MMTs, muscles maintained their length up to 99.7% ± 1.0% of the maximal AF (AF_max). After CL, muscles started to lengthen at 53.0% ± 22.5% of AF_max. For CL-CT, muscles were again able to maintain the static position up to 98.3% ± 5.5% of AF_max. AFiso_max differed highly significantly between CL vs. CL-CT and regular MMT. CL was assumed to generate a slack of muscle spindles, which led to a substantial reduction of the holding capacity. This was immediately erased by a precontraction in the test position. The results substantiate that muscle spindle sensitivity seems to play an important role for neuromuscular functioning and musculoskeletal stability. Full article

We report the case of a tertiary cytoreductive surgery for isolated lymph-node recurrence (ILNR) in a 54-years old Brest cancer 2 (BRCA 2) mutated patients, with a personal history of ovarian cancer previously treated elsewhere. She was admitted to our department for a suspected isolated lymph-nodal pelvic recurrence. A positron emission tomography acquisition with contrast enhanced computed tomography (PET-CT) scan revealed an increased node at the level of the right external iliac (SUV 6.9) in correspondence with the obturator nerve, which was confirmed by transvaginal ultrasound. Since the recurrence was in a single site and the patient had previously undergone three lines of chemotherapy and maintenance with Poly(ADP-ribose) polymerase (PARP) inhibitors, we decided to perform tertiary cytoreductive surgery by minimally invasive laparoscopic approach. After gradual and careful isolation of the obturator nerve, lumbo-sacral trunk and venous vessels afferent to the external and internal iliac vein, the suspected node has been removed. No intra- and postoperative complications occurred. The patient was discharged three days after procedure. We decided to quarterly follow-up; actually, after 16 months no recurrence was detected. Several studies have reported ILNR as a unique clinical disease with low growth rate and less chemosensitivity; this can lead to considered ILNR more susceptible to take advantage of surgical treatment, even in case of second or third recurrence. The BRCA mutational status seems to play a role in the decision-making process in the approach to patients with platinum sensitive relapse of ovarian cancer or in specific isolated forms of recurrence such as the hepatic one. However, data on frequency and prognostic impact of BRCA gene mutation in ILNR are very limited. In this article we investigated the role of BRCA 1 or 2 mutational status in this rare pattern of recurrence according to more recent advances in literature. Full article

Unmyelinated low-threshold mechanoreceptors (C-tactile, CT) in the human skin are important for signaling information about hedonic aspects of touch. We have previously reported that CT-targeted brush stroking by means of a robot reduces experimental mechanical pain. To improve the ecological validity of the stimulation, we developed standardized human–human touch gestures for signaling attention and calming. The attention gesture is characterized by tapping of the skin and is perceived as neither pleasant nor unpleasant, i.e., neutral. The calming gesture is characterized by slow stroking of the skin and is perceived as moderately to very pleasant. Furthermore, the attention (tapping) gesture is ineffective, whereas the calming (stroking) gesture is effective in activating CT-afferents. We conducted an fMRI study (n = 32) and capitalized on the previous development of touch gestures. We also developed an MR compatible stimulator for high-precision mechanical pain stimulation of the thenar region of the hand. Skin-to-skin touching (stroking or tapping) was applied and was followed by low and high pain. When the stroking gesture preceded pain, the pain was rated as less intense. When the tapping gesture preceded the pain, the pain was rated as more intense. Individual pain perception related to insula activation, but the activation was not higher for stroking than for tapping in any brain area during the stimulation period. However, during the evaluation period, stronger activation in the periaqueductal gray matter was observed after calming touch compared to after tapping touch. This finding invites speculation that human–human gentle skin stroking, effective in activating CT-afferents, reduced pain through neural processes involving CT-afferents and the descending pain pathway. Full article

As previously reported, a single test measuring oVEMP n10 to 4000 Hz stimuli (bone-conducted vibration (BCV) or air-conducted sound (ACS)) provides a definitive diagnosis of semicircular canal dehiscence (SCD) in 22 CT-verified patients, with a sensitivity of 1.0 and specificity of 1.0. This single short screening test has great advantages of speed, minimizing testing time, and the exposure of patients to stimulation. However, a few studies of the 4000 Hz test for SCD have reported sensitivity and specificity values which are slightly less than reported previously. We hypothesized that the rise time of the stimulus is important for detecting the oVEMP n10 to 4000 Hz, similarly to what we had shown for 500 and 750 Hz BCV. We measured oVEMP n10 in 15 patients with CT-verified SCD in response to 4000 Hz ACS or BCV stimuli with rise times of 0, 1, and 2 ms. As a result, increasing the rise time of the stimulus reduced the oVEMP n10 amplitude. This outcome is expected from the physiological evidence of guinea pig primary vestibular afferents, which are activated by sound or vibration. Therefore, for clinical VEMP testing, short rise times are optimal (preferably 0 ms). Full article

Ischemic injuries and local hypoxia can result in osteocytes dysfunction and play a key role in the pathogenesis of avascular osteonecrosis. Conventional imaging techniques including magnetic resonance imaging (MRI) and computed tomography (CT) can reveal structural and functional changes within bony anatomy; however, characterization of osteocyte behavioral dynamics in the setting of osteonecrosis at the single cell resolution is limited. Here, we demonstrate an optical approach to study real-time osteocyte functions in vivo. Using nicotinamide adenine dinucleotide (NADH) as a biomarker for metabolic dynamics in osteocytes, we showed that NADH level within osteocytes transiently increase significantly after local ischemia through non-invasive photo-induced thrombosis of afferent arterioles followed by a steady decline. Our study presents a non-invasive optical approach to study osteocyte behavior through the modulation of local environmental conditions. Thus it provides a powerful toolkit to study cellular processes involved in bone pathologies in vivo. Full article

In this paper, we describe and test a new portable device that is able to deliver tactile interoceptive stimulation. The device works by delivering precise interoceptive parasympathetic stimuli to C-tactile afferents connected to the lamina I spinothalamocortical system. In humans, interoceptive stimulation can be used to enhance heart rate variability (HRV). To test the effectiveness of the device in enhancing HRV, 13 subjects were randomly assigned in a single-blind between-subjects design either to the experimental condition or to the control condition. In the experimental condition, subjects received stimulation with the developed device; in the control condition subjects received stimulation with static non-interoceptive pressure. Subjects’ electrocardiograms (ECG) were recorded, with sampling at 1000 Hz for 5 min as a baseline, and then during the stimulations (11 min). Time domain analyses were performed to estimate the short-term vagally mediated component (rMSSD) of HRV. Results indicated that the experimental group showed enhanced rMSSD, compared to the control group. Moreover, frequency domain analyses indicated that high frequency band power, which reflects parasympathetic activity in humans, also appeared to be enhanced in the experimental group compared to control subjects. Conclusions and future challenges for an embodied perspective of rehabilitative medicine are discussed. Full article