Full-length tropomyosin-related kinase B expression in the brainstem in response to persistent inflammatory pain

Renn, Cynthia L.; Lü, Lin; Thomas, Sharon; Dorsey, Susan G.

doi:10.1097/01.wnr.0000215771.61355.e1

Cited by 7 publications

(6 citation statements)

References 26 publications

(52 reference statements)

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“…BDNF exerts effects on nociception by binding to trkB.FL and initiating intracellular signaling cascades that lead to transcriptional changes. Noxious stimulation increases BDNF and trkB.FL production in the spinal dorsal horn [5][6][7][8][9] and brainstem [10,11], leading to hyperalgesia and the formation of nocifensive behaviors. Interfering with trkB.FL signaling via trkB.FL-specific exogenous antibody administration [12] or by blocking receptor activation in the chemicalgenetic transgenic trkB F616A mice [13] prevents the devel-opment of tissue-and nerve injury-induced thermal and mechanical hypersensitivity [14].…”

Section: Resultsmentioning

confidence: 99%

“…All experiments were performed with the tester blind to the genotype of the mice and the treatment that they received. All mice tested were adult male mice (2-6 months of age weighing approximately 30 g. Details regarding the production of the inflammatory model using Complete Freund's adjuvant (CFA) can be found in Renn et al [ 11 ] and the antiretroviral model methods are detailed in Dorsey et al [ 37 ]. For capsaicin experiments, capsaicin (Sigma, St. Louis, MO) was dissolved in 100% dimethylsulfoxide (DMSO) followed by dilution with 0.9% saline to a concentration of 0.08 μg/μl.…”

Section: Methodsmentioning

confidence: 99%

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In Vivo Evidence that Truncated Trkb.T1 Participates in Nociception

2009

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Brain-Derived Neurotrophic Factor (BDNF) is a central nervous system modulator of nociception. In animal models of chronic pain, BDNF exerts its effects on nociceptive processing by binding to the full-length receptor tropomyosin-related kinase B (trkB.FL) and transducing intracellular signaling to produce nocifensive behaviors. In addition to trkB.FL, the trkB locus also produces a widely-expressed alternatively-spliced truncated isoform, trkB.T1. TrkB.T1 binds BDNF with high affinity; however the unique 11 amino acid intracellular cytoplasmic tail lacks the kinase domain of trkB.FL. Recently, trkB.T1 was shown to be specifically up-regulated in a model of HIV-associated neuropathic pain, potentially implicating trkB.T1 as a modulator of nociception. Here, we report that trkB.T1 mRNA and protein is up-regulated in the spinal dorsal horn at times following antiretroviral drug treatment and hind paw inflammation in which nocifensive behaviors develop. While genetic depletion of trkB.T1 did not affect baseline mechanical and thermal thresholds, the absence of trkB.T1 resulted in significant attenuation of inflammation- and antiretroviral-induced nocifensive behaviors. Our results suggest that trkB.T1 up-regulation following antiretroviral treatment and tissue inflammation participates in the development and maintenance of nocifensive behavior and may represent a novel therapeutic target for pain treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

In Vivo Evidence that Truncated Trkb.T1 Participates in Nociception

2009

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“…The neurotrophin BDNF has been shown to be a potent modulator of pain processing in the CNS (Merighi, Salio, Ghirri, & al., 2008). Noxious stimulation increases BDNF production in the spinal dorsal horn (SDH)(Coull, et al, 2005) and brainstem (Renn, Lin, Thomas, & Dorsey, 2006), leading to hyperalgesia and the formation of mechanical allodynia. This is presumably because BDNF signaling participates in the development of windup and central sensitization in the SDH, using mechanisms similar to those in the development of long-term potentiation in the hippocampus (Latremoliere & Woolf, 2009).…”

Section: Discussionmentioning

confidence: 99%

Pain, Genes, and Function in the Post–Hip Fracture Period

Klinedinst

Yerges‐Armstrong

Magaziner

et al. 2016

Pain Management Nursing

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BACKGROUND Post hip fracture generalized pain can lead to a progressive decline in function and greater disability. OBJECTIVES The purpose of this study was to explore the factors that influence pain among older adults post hip fracture, including genetic variability, and evaluate whether or not pain directly or indirectly influenced upper and lower extremity function. METHODS This was a secondary data analysis using data from the first 200 participants in a Baltimore Hip Study (BHS), BHS-7. Assessments were done at 2 months post hip fracture and included age, gender, marital status, education, cognitive status, comorbidities, Body Mass Index (BMI), upper and lower extremity function, single nucleotide polymorphisms (SNPs) from 10 candidate genes, and total areas of pain and pain intensity. Model testing was done using the AMOS statistical program. RESULTS The full sample included 172 participants with an average age of 81. Fifty percent were female and the majority was Caucasian (93%). Model testing was done on 144 individuals whom completed 2 month surveys. Across all models age, cognition and BMI were significantly associated with total areas of pain. Thirty SNPs from five genes (BDNF, FKBP5, NTRK2, NTRK3, and OXTR) were associated with areas of pain and/or pain intensity. Together age, cognition, BMI and the SNP from one of the five genes explained 25% of total areas of pain and 15% of pain intensity. Only age and cognition were significantly associated with lower extremity function and only cognition was significantly associated with upper extremity function. DISCUSSION The full model was partially supported in this study. Our genetic findings related to pain expand prior reports related to BDNF and NTRK2.

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“…An earlier study by Mannion et al [ 72 ] showed that peripheral inflammation and C fiber electrical activity that increased BDNF expression in the DRG also increased full-length TrkB receptor levels in the dorsal horn (also see [ 85 , 101 ]). Even in the brainstem, TrkB levels are elevated in a model of chronic inflammatory pain [ 102 ].…”

Section: Bdnf Is An Important Modulator Of Neural Plasticitymentioning

confidence: 99%

Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

2016

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Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions.

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Full-length tropomyosin-related kinase B expression in the brainstem in response to persistent inflammatory pain

Cited by 7 publications

References 26 publications

In Vivo Evidence that Truncated Trkb.T1 Participates in Nociception

In Vivo Evidence that Truncated Trkb.T1 Participates in Nociception

Pain, Genes, and Function in the Post–Hip Fracture Period

Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

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