Molecular pain research
Chronic pain is a major health problem affecting about 20 per cent of the Swedish population, resulting in markedly reduced quality of life for the individual.
Pain is also a substantial socio-economical problem and the cost for chronic pain in Sweden has been estimated to a staggering 87.5 billion SEK in medical treatment, loss of productivity and disability (SBU, Swedish Council on Health Technology Assessment, 2006).
Unfortunately, there are currently few available effective treatments for chronic pain conditions. Hence, we believe that it is critical to increase our understanding for how chronic pain is regulated in order to identify new treatment strategies and novel drug targets for pain relief.
Current research conducted in our lab
We are currently studying pain in inflammatory conditions, such as rheumatoid arthritis, and we are working together with both preclinical and clinical researchers with a mission to increase our ability to study pain from a translational aspect from bench to bedside.
One noteworthy advance in the field is the insight that not only neurons, but also spinal non-neuronal cells, such as microglia and astrocytes, are involved in the regulation of pain signaling. One line of work in the group is focused on how spinal glia participates in the regulation of pain transmission, and intracellular signaling pathways that are activated or deactivated in astrocytes and/or microglia are being dissected and studied in relation to persistent pain.
We are also investigating regulation of glutamate receptor subunit modulation and cytokine-activated intracellular signaling pathways in spinal neurons in association with inflammation-induced pain. Towards this end the laboratory uses behavioral pharmacology, molecular biology and immunohistochemistry applied to both in vivo and in vitro systems.
Previous group members:
- Merna Bitar, master student
- Ebba Gregory, doctoral student
- Joshua Gregory, post doc
- Max Larsson, researcher
- Nicole Nova, master student
- Johanna Pettersson, master student
- Fatima Rhordo, master student
- Sara Sadek, bachelor student
- Pia Sandberg, bachelor student
- Hanna Steurer, bachelor student
The research in our laboratory is centered on mechanisms that regulate pain signaling, with a particular focus on pain processing in the spinal cord and communication between neurons and glia in the central nervous system. We are investigating the role of both pro- and antiinflammatory signaling pathways and factors in experimental models of inflammation-induced pain, with the aim to pin point novel targets for the development of new pain therapeutics.
Collagen antibody induced arthritis and KBxN arthritis - novel models of pain in arthritic joints
In order to study chronic inflammatory pain we need to identify better models of the clinical problem. After close interactions with rheumatologists we have decided to focus on collagen antibody induced arthritis and KBxN arthritis, two models commonly used to study the disease mechanism in rheumatoid arthritis that prior to our studies have not been used for assessment of arthritis-induced nociception. Together with other preclinical and clinical research groups we strive to create a translational platform for studying the effects of pharmacological treatments of chronic inflammatory pain, with emphasis on interactions between peripheral nociceptive inputs, the immune system and the central nervous system (CNS) as well as changes in endogenous pain modulation during chronic inflammation.
The first part of this project is focused on characterization and validation of the two experimental models of arthritis and identification of pain-related parameters to be used as predictive markers in the assessments of new pain therapies.
In the second part, novel mechanisms of importance for pain transmission are explored using molecular, electrophysiological, behavioral and imaging techniques.
Role of resolvins and lipoxins in inflammatory pain
Resolvins and Lipoxins are important factors in the resolution of inflammation. In this project we are investigating if those anti-inflammatory lipids are also functioning as counter-regulators of pain transduction.
Role of mTOR mediated signaling in inflammation and nerve injury-induced pain
The serine-threonine kinase mammalian target of rapamycin (mTOR) is the core of an important signaling hub that regulates cell growth, cell proliferation and synaptic plasticity downstream of multiple stimuli such as growth factors and cytokines. We are studying this kinase and related factors in both astrocytes and neurons focusing on the role of mTOR in pathological pain.
Spinal AMPA receptor composition and inflammatory pain: role of microglial TNF
TNF alter the ion permeability of glutamate AMPA receptors in the hippocampus. In this project we are studying the links between TNF released from spinal microglia, changes in neuronal AMPA receptor subunit composition and inflammatory pain.
Influence of rat substrain and growth conditions on the characteristics of primary cultures of adult rat spinal cord astrocytes.
J. Neurosci. Methods 2011 Apr;197(1):118-27
Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis.
Pain 2010 Nov;151(2):394-403
Mammalian target of rapamycin in spinal cord neurons mediates hypersensitivity induced by peripheral inflammation.
Neuroscience 2010 Sep;169(3):1392-402
Inflammatory hyperalgesia induces essential bioactive lipid production in the spinal cord.
J. Neurochem. 2010 Aug;114(4):981-93
Release of prostaglandin E(2) and nitric oxide from spinal microglia is dependent on activation of p38 mitogen-activated protein kinase.
Anesth. Analg. 2010 Aug;111(2):554-60
Spinal glial TLR4-mediated nociception and production of prostaglandin E(2) and TNF.
Br. J. Pharmacol. 2010 Aug;160(7):1754-64
Role of spinal p38alpha and beta MAPK in inflammatory hyperalgesia and spinal COX-2 expression.
Neuroreport 2010 Mar;21(4):313-7
Spinal astrocytes in pain processing: non-neuronal cells as therapeutic targets.
Mol. Interv. 2010 Feb;10(1):25-38
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