Browse by Audience
Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5-6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.
Learn More >Interactions between female patients with chronic pain and their medical providers in which providers question or contest the "realness" or nature of their illness experience (e.g. "It's all in your head") have been reported extensively in the extant qualitative literature, particularly for poorly understood ("contested") chronic pain syndromes. Many terms have been offered to describe this talk (e.g. invalidating, dismissive), resulting in conceptual fragmentation and isolated silos of research which together report about one communicative phenomenon. To rectify this fragmentation, the present study offers a meta-synthesis which explores, analyzes, and integrates the findings of 82 qualitative interview studies representing the patient-provider communication experiences of 2,434 female patients living with one or more of 10 chronic overlapping pain conditions (COPCs). COPCs are costly, gendered, and poorly understood. From the meta-synthesis, three key concepts are identified: (1) Functions of disenfranchising talk: Discrediting, silencing, and stereotyping; (2) Effects of disenfranchising talk: Harmed agency, credibility; access to care, support, and resources; and perception of patient-provider relationship; and (3) Responses to disenfranchising talk: Submission, critique, and resistance. Findings confirm the centrality of gender in the experience of disenfranchising talk, underscore the need to adopt an intersectional approach to the study of this talk along additional axes of race and class, and offer heuristic value toward conceptually unifying research about female COPC patients' experiences of disenfranchising talk from providers.
Learn More >Fibromyalgia syndrome (FMS) is a chronic pain condition associated with a significant reduction in health-related quality of life (HRQoL). This study compared the different components of HRQoL between FMS and rheumatoid arthritis (RA) patients, and evaluated the relationships between HRQoL and clinical and emotional factors in FMS and RA patients.
Learn More >The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown.
Learn More >A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments.
Learn More >Nerve injury affecting the upper limb is a leading cause of lifelong disability. Damage to the nerves in the arm often causes weakness and somatosensory dysfunction ranging from numbness to pain. Previous studies show that combining brief bursts of electrical vagus nerve stimulation (VNS) with motor or tactile rehabilitation can restore forelimb function after median and ulnar nerve injury, which causes hyposensitivity of the ventral forelimb. Here, we sought to determine whether this approach would be similarly effective in a model of radial nerve injury that produces allodynia in the ventral forelimb. To test this, rats underwent complete transection of the radial nerve proximal to the elbow followed by tubular repair. In the first experiment, beginning ten weeks after injury, rats received six weeks of tactile rehabilitation, consisting of mechanical stimulation of either the dorsal or ventral region of the forepaw in the injured limb, with or without concurrent VNS. In a second experiment, a separate cohort of rats underwent six weeks of forelimb motor rehabilitative training with or without paired VNS. Contrary to findings in previous models of hyposensitivity, VNS therapy fails to improve recovery of either somatosensory or motor function in the forelimb after radial nerve injury. These findings describe initial evidence that pain may limit the efficacy of VNS therapy and thus highlight a characteristic that should be considered in future studies that seek to develop this intervention.
Learn More >Metformin is a well-tolerated antidiabetic drug and has recently been repurposed for numerous diseases, including pain. However, a higher dose of metformin is required for effective analgesia, which can potentiate its dose-dependent gastrointestinal side effects. Curcumin is a natural polyphenol and has beneficial therapeutic effects on pain. Curcumin has been used as an analgesic adjuvant with several analgesic drugs, allowing synergistic antinociceptive effects. Nevertheless, whether curcumin can exert synergistic analgesia with metformin is still unknown. In the present study, the nature of curcumin-metformin anti-inflammatory interaction was evaluated in in vitro using lipopolysaccharide-induced RAW 264.7 macrophage and BV-2 microglia cells. In both macrophage and microglia, curcumin effectively potentiates the anti-inflammatory effects of metformin, indicating potential synergistic effects in both peripheral and central pathways of pain. The nature of the interaction between curcumin and metformin was further recapitulated using a mouse model of formalin-induced pain. Coadministration of curcumin and metformin at a 1:1 fixed ratio of their ED doses significantly reduced the dose required to produce a 50% effect compared to the theoretically required dose in phase II of the formalin test with a combination index value of 0.24. Besides, the synergistic interaction does not appear to involve severe CNS side effects indicated by no motor alterations, no alterations in short-term and long-term locomotive behaviors, and the general well-being of mice. Our findings suggest that curcumin exerts synergistic anti-inflammation with metformin with no potential CNS adverse effects.
Learn More >In vitro models of the peripheral nervous system would benefit from further refinements to better support studies on neuropathies. In particular, the assessment of pain-related signals is still difficult in human cell cultures. Here, we harnessed induced pluripotent stem cells (iPSCs) to generate peripheral sensory neurons enriched in nociceptors. The objective was to generate a culture system with signaling endpoints suitable for pharmacological and toxicological studies. Neurons generated by conventional differentiation protocols expressed moderate levels of P2X3 purinergic receptors and only low levels of TRPV1 capsaicin receptors, when maturation time was kept to the upper practically useful limit of 6 weeks. As alternative approach, we generated cells with an inducible NGN1 transgene. Ectopic expression of this transcription factor during a defined time window of differentiation resulted in highly enriched nociceptor cultures, as determined by functional (P2X3 and TRPV1 receptors) and immunocytochemical phenotyping, complemented by extensive transcriptome profiling. Single cell recordings of Ca2+-indicator fluorescence from >9000 cells were used to establish the "fraction of reactive cells" in a stimulated population as experimental endpoint, that appeared robust, transparent and quantifiable. To provide an example of application to biomedical studies, functional consequences of prolonged exposure to the chemotherapeutic drug oxaliplatin were examined at non-cytotoxic concentrations. We found (i) neuronal (allodynia-like) hypersensitivity to otherwise non-activating mechanical stimulation that could be blocked by modulators of voltage-gated sodium channels; (ii) hyper-responsiveness to TRPV1 receptor stimulation. These findings and several other measured functional alterations indicate that the model is suitable for pharmacological and toxicological studies related to peripheral neuropathies.
Learn More >The aim of this qualitative research is to deepen the knowledge in the field of psycho-oncology and the consequences of chronic and persistent pain by listening to patients' experiences, their emotions and difficulties in facing this hard condition, and assessing their perception of the role of the psychologist in pain management. In this qualitative study, a semistructured interview was used, designed from three research questions: chronic pain and quality of life; chronic pain and psychological well-being; and the role and perception of the psychologist in pain management. The sample consists of 29 women who suffered or have recovered from breast carcinoma, and who currently report having chronic pain due either to the presence of the cancer or as a result of surgery or treatment. Three themes emerged from the thematic analysis: quality of life and psychological well-being, relational well-being, and perception and role of the psychologist. Two subthemes have been identified for each theme: common features of chronic pain and consequences and resilience for the first theme; not feeling understood and willingness to protect loved ones for the second theme; and improvements perceived by users and reasons for not making use of the service for the last theme. In conclusion, the results obtained from the literature and those from the analysis of the interviews are discussed and compared, and reflections are made on possible future implications.
Learn More >The somatosensory system processes diverse types of information including mechanical, thermal, and chemical signals. It has an essential role in sensory perception and body movement and, thus, is crucial for organism survival. The neural network for processing somatosensory information comprises multiple key nodes. Spinal projection neurons represent the key node for transmitting somatosensory information from the periphery to the brain. Although the anatomy of spinal ascending pathways has been characterized, the mechanisms underlying somatosensory information processing by spinal ascending pathways are incompletely understood. Recent studies have begun to reveal the diversity of spinal ascending pathways and their functional roles in somatosensory information processing. Here, we review the anatomic, molecular, and functional characteristics of spinal ascending pathways.
Learn More >