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Myofascial pain syndrome (MPS) is a type of skeletal pain identified by myofascial trigger points (MTrPs). The formation of MTrPs is linked to muscle damage. The fibroblast growth factor receptor (FGFR1) has been found to cause pain sensitivity while repairing tissue damage. The aim of the current study was to explore the mechanism of FGFR1 in MTrPs. We used a RayBio human phosphorylation array kit to measure p-FGFR1 levels in human control subjects and patients with MTrPs. P-FGFR1 was upregulated in the patients with MTrPs. Then a rat model of myofascial pain syndrome was established by a blunt strike on the left gastrocnemius muscles (GM) and eccentric-exercise for 8 weeks with 4 weeks of recovery. After establishing the myofascial pain syndrome model, the morphology of the GM changed, and the differently augmented sizes of round fibres (contracture knots) in the transverse section and fusiform shapes in the longitudinal section were clearly seen in the rats with myofascial pain. The expression of p-FGFR1 was upregulated on the peripheral nerves and dorsal root ganglion (DRG) neurons in the MTrPs group. The spinal Fos protein expression was increased in the MTrPs group. Additionally, the mechanical pain threshold was reduced, and the expression of FGF2, p-FGFR1, PI3K-p110γ, and p-AKT increased in the MTrPs group. PD173074 increased the mechanical pain threshold of the MTrPs group, and inhibited the expression of p-FGFR1, PI3K-p110γ, and p-AKT. Moreover, LY294002 increased the mechanical pain threshold of the MTrPs group. These findings suggest that FGFR1 may regulate myofascial pain in rats through the PI3K/AKT pathway.
Learn More >Mental disorders including anxiety and depression are common comorbidities in fibromyalgia patients, and exert a profound impact on their quality of life. Mirogabalin, a novel ligand for the αδ-subunit of voltage-gated calcium channels, shows analgesic effects in fibromyalgia and neuropathic pain models. To provide additional information regarding its potential utility for treating chronic pain, we examined its anxiolytic-like effects in rats repeatedly injected with acidic saline intramuscularly (Sluka model), as an experimental fibromyalgia model.
Learn More >Quantitative sensory testing (QST) may help predict treatment responses in individuals with chronic pain. Our objective was to determine if evoked pain sensitivity at baseline predicted preferential treatment responses to either emotional awareness and expression therapy (EAET) or cognitive behavioral therapy (CBT) in individuals with fibromyalgia.
Learn More >Chronic allergic itch is a common symptom affecting millions of people and animals, but its pathogenesis is not fully explained. Herein, we show that periostin, abundantly expressed in the skin of patients with atopic dermatitis (AD), induces itch in mice, dogs, and monkeys. We identify the integrin αβ3 expressed on a subset of sensory neurons as the periostin receptor. Using pharmacological and genetic approaches, we inhibited the function of neuronal integrin αβ3, which significantly reduces periostin-induced itch in mice. Furthermore, we show that the cytokine TSLP, the application of AD-causing MC903 (calcipotriol), and house dust mites all induce periostin secretion. Finally, we establish that the JAK/STAT pathway is a key regulator of periostin secretion in keratinocytes. Altogether, our results identify a TSLP-periostin reciprocal activation loop that links the skin to the spinal cord via peripheral sensory neurons, and we characterize the non-canonical functional role of an integrin in itch.
Learn More >Paclitaxel use in cancer treatment is limited by a painful syndrome that has no effective treatment. Despite new therapies, drugs of the World Health Organization (WHO) analgesic ladder remain a useful therapeutic tool for cancer pain relief. Since cancer pain is caused by both tumor and chemotherapy, we assessed the efficacy of drugs from the WHO analgesic ladder for cancer pain relief in a paclitaxel-induced pain syndrome (P-IPS) model. P-IPS was induced in rats by one or four injections of paclitaxel on alternate days. The acute and chronic phases were assessed 24 h and 15 days after the first paclitaxel injection, respectively. The mechanical allodynia was evaluated after (step 1 of the ladder) paracetamol, (step 2) codeine alone or plus paracetamol and (step 3) morphine treatment in the acute or chronic phase of P-IPS. Paracetamol, codeine and morphine were equally efficacious in reducing the acute phase of the P-IPS. Codeine plus paracetamol had similar efficacy and potency when administered together in the acute phase of the P-IPS, but produced a longer-lasting effect than when separately managed. Moreover, paracetamol, codeine and morphine partially reduced the chronic phase of P-IPS, losing their efficacy and, in the case of codeine, potency when compared to the acute phase. However, paracetamol plus codeine increased the potency and efficacy of the codeine when compared to codeine administered alone in the chronic phase of P-IPS, producing a long-lasting anti-allodynic effect. Together, analgesics of WHO analgesic ladder reduce both acute and chronic phases of P-IPS, with codeine plus paracetamol presenting more potent, efficacious and long-lasting effect. Thus, in addition to tumor pain, drugs of WHO analgesics ladder could also be useful to treat P-IPS.
Learn More >Trigeminal neuralgia (TN) is debilitating and is usually accompanied by mood disorders. The lateral habenula (LHb) is considered to be involved in the modulation of pain and mood disorders, and the present study aimed to determine if and how the LHb participates in the development of pain and anxiety in TN. To address this issue, a mouse model of partial transection of the infraorbital nerve (pT-ION) was established. pT-ION induced stable and long-lasting primary and secondary orofacial allodynia and anxiety-like behaviors that correlated with the increased excitability of LHb neurons. Adeno-associated virus (AAV)-mediated expression of hM4D(Gi) in glutamatergic neurons of the unilateral LHb followed by clozapine-N-oxide application relieved pT-ION-induced anxiety-like behaviors but not allodynia. Immunofluorescence validated the successful infection of AAV in the LHb, and microarray analysis showed changes in gene expression in the LHb of mice showing allodynia and anxiety-like behaviors after pT-ION. Among these differentially expressed genes was Tacr3, the downregulation of which was validated by RT-qPCR. Rescuing the downregulation of Tacr3 by AAV-mediated Tacr3 overexpression in the unilateral LHb significantly reversed pT-ION-induced anxiety-like behaviors but not allodynia. Whole-cell patch clamp recording showed that Tacr3 overexpression suppressed nerve injury-induced hyperexcitation of LHb neurons, and western blotting showed that the pT-ION-induced upregulation of p-CaMKII was reversed by AAV-mediated Tacr3 overexpression or chemicogenetic inhibition of glutamatergic neurons in the LHb. Moreover, not only anxiety-like behaviors, but also allodynia after pT-ION were significantly alleviated by chemicogenetic inhibition of bilateral LHb neurons or by bilateral Tacr3 overexpression in the LHb. In conclusion, Tacr3 in the LHb plays a protective role in treating trigeminal nerve injury-induced allodynia and anxiety-like behaviors by suppressing the hyperexcitability of LHb neurons. These findings provide a rationale for suppressing unilateral or bilateral LHb activity by targeting Tacr3 in treating the anxiety and pain associated with TN.
Learn More >The effect of headache on cognitive performance is controversial, due to conflicting results obtained from studies in clinical or population settings. We aimed to understand if migraine and other headaches modify the rates of decline on different cognitive measures, during a 5-year interval.
Learn More >We aimed to assess the efficacy and safety of erenumab, a fully human monoclonal antibody inhibiting the calcitonin gene-related peptide receptor (CGRPr), for the prevention of migraine in a real-life setting.
Learn More >Chronic pain causes significant suffering, limitation of daily activities and reduced quality of life. Infection from COVID-19 is responsible for an ongoing pandemic that causes severe acute respiratory syndrome, leading to systemic complications and death. Led by the World Health Organization, healthcare systems across the world are engaged in limiting the spread of infection. As a result all elective surgeries, procedures, and patient visits, including pain management services, have been postponed or cancelled. This has impacted the care of chronic pain patients. Most are elderly with multiple comorbidities, which puts them at risk of COVID-19 infection. Important considerations that need to be recognised during this pandemic for chronic pain patients include: ensuring continuity of care and pain medications, especially opioids; use of telemedicine; maintaining biopsychosocial management; use of anti-inflammatory drugs; use of steroids; and prioritising necessary procedural visits. There are no guidelines to inform physicians and healthcare providers engaged in caring for patients with pain during this period of crisis. We assembled an expert panel of pain physicians, psychologists and researchers from North America and Europe to formulate recommendations to guide practice. As the COVID-19 situation continues to evolve rapidly, these recommendations are based on the best available evidence and expert opinion at this present time and may need adapting to local workplace policies.
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