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Trigeminal neuralgia is considered the worst pain a human being can experience. Initial treatment utilizes anticonvulsant sodium channel blockers, which relieve pain in approximately 70% of patients. In refractory cases, it is possible to perform ablative treatments decompressive surgeries and neuromodulatory techniques. This report describes the treatment of a patient with refractory trigeminal neuralgia, remaining with a painful clinical picture after four surgical procedures and three ablative procedures. A dorsal root ganglion (DRG) stimulation electrode was implanted in the trigeminal ganglion, through intraoral puncture with maxillary fixation of the electrode, in order to minimize the chances of displacement. The test phase consisted of implanting a quadripolar electrode for DRG stimulation through puncture lateral to the buccal rim in a fluoroscopic coaxial view. The electrode was fixed to the skin and maintained for five days, during which the patient remained completely pain-free. After the test, the definitive implant was performed, now with intraoral puncture and maxillary electrode fixation. The patient presented with severe pain (verbal numerical scale between 9 and 10), manifesting an evident suicidal ideation. After a five-day test period, the definitive stimulation electrode was implanted through intraoral puncture. The patient remains pain-free in the three-month follow-up to the present, with no displacement of the electrode. The dorsal root ganglion electrode may be considered a therapeutic option in patients with severe trigeminal neuralgia. Controlled studies must be performed in order to determine the efficacy and safety of the method.
Learn More >Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.
Learn More >Low back pain (LBP) is a global and disabling problem. A considerable number of systematic reviews published over the past decade have reported a range of factors that increase the risk of chronicity due to LBP. This study summarizes up-to-date and high-level research evidence on the biopsychosocial prognostic factors of outcomes in adults with non-specific low back pain at follow-up. An umbrella review was carried out. PubMed, the Cochrane Database of Systematic Reviews, Web of Science, PsycINFO, CINAHL Plus and PEDro were searched for studies published between 1 January 2008 and 20 March 2020. Two reviewers independently screened abstracts and full texts, extracted data and assessed review quality. Fifteen systematic reviews met the eligibility criteria; all were deemed reliable according to our criteria. There were five prognostic factors with consistent evidence of association with poor acute-subacute LBP outcomes in the long term (high levels of pain intensity and disability, high emotional distress, negative recovery expectations and high physical demands at work), as well as one factor with consistent evidence of no association (low education levels). For mixed-duration LBP, there was one predictor consistently associated with poor outcomes in the long term (high pain catastrophism). We observed insufficient evidence to synthesize social factors as well as to fully assess predictors in the chronic phase of LBP. This study provides consistent evidence of the predictive value of biological and psychological factors for LBP outcomes in the long term. The identified prognostic factors should be considered for inclusion into low back pain explanatory models.
Learn More >Invited Clinical Commentary BACKGROUND: Arthritis is one of the most frequently reported causes of disability in the United States and the prevalence is expected to increase in the coming decades. While many rheumatic diseases involve hand impairments, most are systemic and involve more than the musculoskeletal system. Functional and work disability are high and people would benefit from the services of occupational and physical therapists.
Learn More >Mechanical allodynia impinges on the life quality of patients. Hen Egg Lysozyme (HEL) is a substance extracted from eggs that is commonly used to inhibit bacterial activity. The role of HEL in regulating and treating pain is unclear. Here, we find that HEL selectively attenuates static mechanical allodynia of mice induced by complete Freund's adjuvant (CFA), spinal nerve ligation (SNL) and chemotherapeutic agent. RNA-seq screening reveals that CFA significantly reduces the expression of Parkin in dorsal root ganglion (DRG) neurons of mice, while pre-administration of HEL increases the expression of Parkin and remits the static mechanical allodynia induced by Parkin-siRNA. Moreover, HEL increases the interaction between nuclear respiratory factor 1 (NRF1) and histone acetyltransferase P300 and then enhances the NRF1 mediated histone acetylation in prkn promoter region in DRGs of mice. Further, Parkin interacts with mechanotransducing ion channel TACAN (Tmem120a) and knockdown of Parkin significantly increases the membrane trafficking of TACAN in sensory neurons of mice. While pre-administration of HEL inhibits the increased membrane trafficking of TACAN in sensory neurons of mice induced by Parkin-siRNA. In addition, pre-given of HEL also significantly attenuates the static mechanical allodynia induced by overexpression of TACAN in mice, and the effect of HEL can be blocked by Parkin-siRNA. This indicates that HEL increases the expression of Parkin through epigenetic mechanisms and then decreases TACAN membrane trafficking in sensory neurons to relieve static mechanical hypersensitivity. Therefore, we reveal a novel function of HEL, which is a potential substance for the treatment of static mechanical pain.
Learn More >Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics. It has been reported that enriched environment (EE), as a new way of endogenous pharmacotherapy, is effective in attenuating chronic inflammatory pain. However, the underlying molecular mechanisms are still not fully understood. NMDA NR2B receptor plays a critical role in pain transmission and modulation. Thus, in this study, we aimed at the effect of EE on the NR2B receptors expression in the prefrontal cortex, hippocampus and thalamus in the inflammatory pain mice. The results showed a significant increase of NR2B receptors in the thalamus of mice at 7 d following injection of CFA in the subcutaneous of the bottom of the left hind paw. EE significantly reduced the duration of mechanical hypersensitivity and anxiety-related behavior and the expression of NR2B receptors as compared to the standard condition. Furthermore, EE significantly increased 2-arachidonoylglycero (2-AG) levels at 7 d in the inflammatory pain mice as compared to the standard condition, and the effect of EE on the behavior and the expression of NR2B receptors was abolished by intraperitoneal injection of AM281 (a selective antagonist of CB1 receptor). Elevated 2-AG levels by intraperitoneal injection of JZL184 (a selective inhibitor of MAGL, the enzyme responsible for 2-AG hydrolysis) produced the same effect as EE. Results from this study provide the evidence that EE mimics endocannabinoids to take analgesic and anti-anxiety activities by decreasing the expression of the NR2B receptors via the CB1 receptor in the thalamus, pending further studies.
Learn More >Whether neuroinflammation causes comorbid mood disorders in neuropathic pain remains elusive. Here we investigated the role of high mobility group box 1 protein (HMGB1), a proinflammatory cytokine, in the medial prefrontal cortex (mPFC) in anxiety comorbidity of neuropathic pain.
Learn More >Spinal cord injury (SCI) can result in a partial or complete loss of motor and sensory function below the injured segment, which has a significant impact on patients' quality of life and places a significant social burden on them. Long non-coding RNA (LncRNA) is a 200-1000 bp non-coding RNA that has been shown to have a key regulatory role in the progression of a variety of neurological illnesses. Many studies have demonstrated that differentially expressed LncRNAs following spinal cord injury can participate in inflammatory damage, apoptosis, and nerve healing by functioning as competitive endogenous RNA (ceRNA); at the same time, it has a significant regulatory effect on sequelae such neuropathic pain. As a result, we believe that LncRNAs could be useful as a molecular regulatory target in the diagnosis, treatment, and prognosis of spinal cord injury.
Learn More >Monosodium glutamate induces behaviors thought to reflect headache and nausea in rats. We explored the effects of the N-methyl-D-aspartate receptor antagonist (2R)-amino-5-phosphonovaleric acid, the inotropic glutamate receptor antagonist kynurenic acid, and the CGRP receptor antagonist olcegepant, on monosodium glutamate-induced increases in nocifensive, headache-like and nausea behaviours. Effects of these antagonists on motor function were examined with a rotarod. The effect of the dopamine receptor antagonist metoclopramide and the serotonin 3 receptor antagonist ondansetron on nausea behaviour was also assessed. (2R)-amino-5-phosphonovaleric acid, and to a lesser extent, kynurenic acid and olcegepant, reduced nocifensive and headache-like behaviours evoked by monosodium glutamate. No alteration in motor function by (2R)-amino-5-phosphonovaleric acid, kynurenic acid or olcegepant was observed. No sex-related differences in the effectiveness of these agents were identified. Nausea behaviour was significantly more pronounced in male than in female rats. Olcegepant, ondansetron and metoclopramide ameliorated this nausea behaviour in male rats. Ondansetron and metoclopramide also reduced headache-like behaviour in male rats. These findings suggest that peripheral N-methyl-D-aspartate receptor activation underlies monosodium glutamate-induced headache-like behaviour but does not mediate the nausea behaviour in rats.
Learn More >Endometriosis is a chronic estrogen-dependent disease that afects one out of ten women worldwide leading to chronic pelvic pain and infertility. Despite decades of research endometriosis still represents a challenge for doctors and patients in terms of diagnosis and treatment. Current options for the appropriate pharmacotherapy in women with pain-related endometriosis are well described in the several other guidelines but high-quality evidence is not available for all. The medical treatment of endometriosis relies on hormonal medications that block menstruation in attempt to control pain and hopefully delay or avoid surgery. Thorough medical evaluation is mandatory to identify other causes of pelvic pain such as irritable bowel syndrome, interstitial cystitis and myofascial pain as well as rule out obstructive disease and suspicious adnexal masses. Drug choice should be individualized taking into consideration the side-effects profile as well as tolerability, costs, risks and benefits as one size does not fit all.As we gain more knowledge on the pathological cascade leading to endometriosis, the possibility of identifying specific agents which could block essential pathways and prevent disease progression and development increases.
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