[Show abstract][Hide abstract] ABSTRACT: Cytokines and oxygen free radicals have been implicated in the potential pathogenic development of complex regional pain syndrome (CRPS). We aimed to analyze the relationship between clinical status, circulating levels of cytokines, and markers of oxidative damage during the treatment with anti-TNFα antibodies. The patient chosen for treatment had not had improvement through a number of conventional therapies and fulfilled the current diagnostic criteria for CRPS-1. We investigated the clinical variables before and after systemic administration of 1.4 mg/kg anti-TNFα antibody (infliximab), repeated after 1 month in a dose of 3 mg/kg. Blood samples were collected before and after anti-TNFα antibodies administration, and plasma was analyzed for 8-isoprostane-prostaglandin F2α (8-iso-PGF2α, a marker of oxidative injury) and cytokines (TNF-α, IL-4, IL-6, IL-7, IL-8, IL-10, IL-17A). Plasma concentrations of 8-iso-PGF2α were measured with radioimmunoassay (RIA), and the kinetics of cytokines were detected in plasma by antibody-based proximity ligation (PLA). Pathologically high levels of 8-iso-PGF2α were found in the patient. Immediately after each administration of infliximab, the levels of 8-iso-PGF2α decreased. Although the patient showed an improvement of the cutaneous dystrophic symptoms and diminished pain associated with these lesions, the levels of circulating TNFα increased after the administration of anti-TNFα antibodies. In a patient with CRPS-1 treated with anti-TNFα antibodies, we report increased levels of circulating TNFα and a temporary mitigation of oxidative stress as measured by plasma F(2) -isoprostane. This case report provides evidence 2 supporting the indication of monitoring the oxidative stress biomarkers during treatment with anti-TNFα antibodies in CRPS 1.
Pain Practice 01/2013; 13(8). DOI:10.1111/papr.12027 · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ablating or functionally compromising sets of sensory neurons has provided important insights into peripheral modality-specific wiring in the somatosensory system. Inflammatory hyperalgesia, cold pain, and noxious mechanosensation have all been shown to depend upon Na(v)1.8-positive sensory neurons. The release of fast-acting neurotransmitters, such as glutamate, and more slowly released neuropeptides, such as substance P (SP), contribute to the diversified responses to external stimuli. Here we show that deleting Vglut2 in Na(v)1.8(Cre)-positive neurons compromised mechanical pain and NGF-induced thermal hyperalgesia, whereas tactile-evoked sensation, thermal, formalin-evoked, and chronic neuropathic pain were normal. However, when Vglut2(f/f);Na(v)1.8(Cre) mice were injected with a SP antagonist before the formalin test, the second phase pain response was nearly completely abolished, whereas in control mice, the pain response was unaffected. Our results suggest that VGLUT2-dependent signaling originating from Na(v)1.8-positive neurons is a principal sensing mechanism for mechanical pain and, together with SP, inflammatory pain. These data define sets of primary afferents associated with specific modalities and provide useful genetic tools with which to analyze the pathways that are activated by functionally distinct neuronal populations and transmitters.
Proceedings of the National Academy of Sciences 03/2011; 108(14):5789-94. DOI:10.1073/pnas.1013602108 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Finding predisposing factors or vulnerability genes for chronic pain development would provide opportunities to tailor treatment for each patient. Such knowledge also pinpoints crucial functions required for the pathophysiological process. Both these outcomes are necessary for further improving chronic pain prevention and treatment.Pain can be modulated by a myriad of processes including endogenous opioid production, inflammation and tissue repair, which can trigger synaptic plasticity both centrally and peripherally, affecting both excitatory and inhibitory signaling by neurons, as well as glial signaling contributing to these processes. The genetic foundation for this web of interactions should provide future drug targets for chronic pain prevention and treatment. As the body of data grows, with increased patient cohort sizes, and more standardized characterizations of the pain state, we can hope to identify many new gene candidates for treatment of chronic pain.We are convinced that pain researchers in the Nordic countries have excellent possibilities for networking and cooperation, to carry out successful projects in the field of the genetics of pain. The “New Scandinavian Association for the Study of Pain” (newSASP) may provide an important facilitating arena to achieve this goal.
Scandinavian Journal of Pain 05/2009; 1. DOI:10.1016/S1877-8860(09)70006-0