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In the context of neuropathic pain, the contribution of regeneration to the development of positive symptoms is not completely understood. Several efforts have been done to described changes in axotomized neurons, however, there is scarce data on changes occurring in intact neurons, despite experimental evidence of functional changes. To address this issue, we analyzed by immunohistochemistry the presence of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), an accepted marker of regeneration, within DRGs where axotomized neurons were retrogradely labeled following peripheral nerve injury. Likewise, we have characterized abnormal electrophysiological properties in intact fibers after partial nerve injury.
Learn More >To ensure an adequate pain therapy with high patient adherence, it is necessary to know and consider patient preferences. A discrete choice experiment (DCE) was used to obtain patients' preferences regarding treatment with systemic or topical pain medication. Patients with peripheral neuropathic pain (pNP) were recruited in two pain-focused practices in Germany. To identify relevant attributes of topical or systemic pain medication, a literature review and face-to-face interviews with experts for pain treatment were conducted. The attributes used in the choice scenarios were noticeable onset of effect, time spent in medical office, risk of systemic and local side effects, impairment of daily life with regards to sleep quality and sexuality. The model was estimated with a mixed multinomial logit regression model. The study included 153 participants suffering from moderate to severe pNP. Most important attributes from patient's perspective was noticeable onset of effect (Odds Ratio 2.141 [95%-Confidence Interval 1.837 – 2.494]), followed by risk of systemic side effects (2.038 [1.731 – 2.400]), risk of sexual dysfunction (1.839 [1.580 – 2.140]), while risk of local side effects regarding skin ranked fourth (1.612 [1.321 – 1.966]).The impairment of sleep quality was also significant but less important (1.556 [1.346 – 1.798]). Local side effects were more likely to be accepted than systemic side effects. The risks of sexual dysfunction as a side effect of treatment are very important for patients, although it has received little attention in the literature.
Learn More >The Central Sensitization Inventory (CSI) is often used in clinical settings to screen for the presence of central sensitization. However, various cutoff scores have been reported for this tool, and scores have not been consistently associated with widespread pain sensitivity as measured with quantitative sensory testing (QST). The purpose of this study was to compare QST profiles among asymptomatic controls and participants with chronic musculoskeletal pain (CMP), and to determine the association between self-report questionnaires and QST in participants with CMP.
Learn More >Persistent pain during pregnancy is a significant health issue, which could be correlated with psychological distress resulting from inadequate social support. This study aims to investigate whether the relationship between poor social support and antenatal pain is mediated by psychological distress. We also aimed to examine whether social cohesion moderates the influence of psychological distress on the relationship between social support and antenatal pain.
Learn More >Smokers have a higher incidence of chronic pain than non-smokers, but the neural mechanism is not yet fully understood. Nicotine is the main component of tobacco and acts as an agonist for nicotinic cholinergic receptors (nAChRs) in the nervous system. This study was approved by the IACUC of UM. The effects of chronic nicotine administration on mechanical sensitivity were studied using a rat model. The changes in the expression levels of the α7 isoform of nAChR (α7-nAChR), inflammatory cytokines TNFα and COX-2, as well as the density of neuro-immune cells (astrocytes and microglia) were measured concurrently. The results indicate that long-term nicotine administration induces hypersensitivity to mechanical stimuli, as demonstrated by a significant reduction in the pain perception threshold. In response to nicotine, the expression levels of α7-nAChR increased in the periaqueductal gray matter (PAG) and decreased in the spinal cord. Acute administration of the selective α7-nAChR agonist CDP-Choline reversed this hypersensitivity. Chronic nicotine administration led to an increase of microglial cells in the dorsal horn of the spinal cord and increased expression levels of the cytokines TNFα and COX-2. This study suggests that decreased α7-nAChR expression in the spinal cord, as a result of long-term exposure to nicotine, may be causatively linked to chronic pain. Simultaneously, the increase of neuro-immune factors in the spinal cord is also a potential factor leading to chronic pain.
Learn More >Central sensitization is one of the important pathological mechanisms of chronic migraine (CM). Metabolic glutamate receptor 5 (mGluR5) mediates pain by activating various intracellular pathways. However, whether mGluR5 contributes to central sensitization in CM and the exact mechanism remains unclear. Male rats were used to establish a CM model by repeated infusions of inflammatory soup (IS) for 7 days to stimulate the activation of the dural nociceptor. The mechanical and thermal thresholds were used to evaluate allodynia, and central sensitization was assessed by measuring calcitonin gene-related peptide (CGRP) and substance P (SP). Microtubule associated protein 1 light chain 3 (LC3) and p62/SQSTM1 were used to assess autophagy. We found that the expression of mGluR5 in the trigeminal nucleus caudalis (TNC) of CM rats was significantly increased. In addition, the downregulation of mGluR5 activated autophagy by inhibiting the mTOR pathway. Moreover, the activation of autophagy alleviated allodynia and central sensitization in CM rats. This study identified a novel strategy for the treatment of CM; the downregulation of mGluR5 in a rat model of CM decreased the expression of the inflammatory factor interleukin-1 beta (IL-1β) and the central sensitization-associated proteins CGRP and SP by activating autophagy via inhibiting the mTOR pathway.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse event associated with treatment with paclitaxel and other chemotherapeutic agents. The prevention and treatment of CIPN are limited by a lack of understanding of the molecular mechanisms underlying this toxicity. In the current study, a human induced pluripotent stem cell-derived sensory neuron (iPSC-SN) model was developed for the study of chemotherapy-induced neurotoxicity. The iPSC-SNs express proteins characteristic of nociceptor, mechanoreceptor, and proprioceptor sensory neurons and show Ca influx in response to capsaicin, α,β-meATP, and glutamate. The iPSC-SNs are relatively resistant to the cytotoxic effects of paclitaxel, with half-maximal inhibitory concentration (IC ) values of 38.1 µM (95% confidence interval (CI) 22.9-70.9 µM) for 48-hour exposure and 9.3 µM (95% CI 5.7-16.5 µM) for 72-hour treatment. Paclitaxel causes dose-dependent and time-dependent changes in neurite network complexity detected by βIII-tubulin staining and high content imaging. The IC for paclitaxel reduction of neurite area was 1.4 µM (95% CI 0.3-16.9 µM) for 48-hour exposure and 0.6 µM (95% CI 0.09-9.9 µM) for 72-hour exposure. Decreased mitochondrial membrane potential, slower movement of mitochondria down the neurites, and changes in glutamate-induced neuronal excitability were also observed with paclitaxel exposure. The iPSC-SNs were also sensitive to docetaxel, vincristine, and bortezomib. Collectively, these data support the use of iPSC-SNs for detailed mechanistic investigations of genes and pathways implicated in chemotherapy-induced neurotoxicity and the identification of novel therapeutic approaches for its prevention and treatment.
Learn More >Dorsal root ganglion stimulation (DRGS) is a promising neurostimulation modality in the treatment of painful polyneuropathy. The aim of this prospective pilot study was to investigate the effect of DRGS on pain intensity in patients with intractable painful polyneuropathy.
Learn More >The purpose of this study was to evaluate the effects of trigger point (TrP) dry needling alone or as an adjunct to other interventions on pain intensity and related disability in nontraumatic shoulder pain.
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