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Blomqvist, Anders
Publications (10 of 79) Show all publications
Zajdel, J., Zager, A., Blomqvist, A., Engblom, D. & Shionoya, K. (2019). Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation. Brain, behavior, and immunity, 77, 141-149
Open this publication in new window or tab >>Acute maternal separation potentiates the gene expression and corticosterone response induced by inflammation
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2019 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 77, p. 141-149Article in journal (Refereed) Published
Abstract [en]

Maternal care is crucial for infants and profoundly affects their responses to different kinds of stressors. Here, we examined how maternal separation affects inflammatory gene expression and the corticosterone response to an acute immune challenge induced by lipopolysaccharide (LPS; 40 µg/kg ip) in mouse pups, 8–9 days old. Maternal separation initially attenuated LPS-induced hypothalamic pro-inflammatory gene expression, but later, at 3 h after immune challenge, robustly augmented such gene expression and increased serum corticosterone levels. Providing the pups with a warm and soft object prevented the separation-induced augmented hypothalamic-pituitary-adrenal (HPA)-axis response. It also prevented the potentiated induction of some, but not all, inflammatory genes to a similar extent as did the dam. Our results show that maternal separation potentiates the inflammatory response and the resulting HPA-axis activation, which may have detrimental effects if separation is prolonged or repeated.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Lipopolysaccharide, Hypothalamus, Cytokines, Inflammation, Maternal separation, Corticosterone
National Category
Pharmacology and Toxicology Developmental Biology Medical Biotechnology Immunology
Identifiers
urn:nbn:se:liu:diva-154886 (URN)10.1016/j.bbi.2018.12.016 (DOI)30590109 (PubMedID)2-s2.0-85059128986 (Scopus ID)
Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-04-08Bibliographically approved
Klawonn, A., Fritz, M., Nilsson, A., Bonaventura, J., Shionoya, K., Mirrasekhian, E., . . . Engblom, D. (2018). Motivational valence is determined by striatal melanocortin 4 receptors. Journal of Clinical Investigation, 128(7), 3160-3170
Open this publication in new window or tab >>Motivational valence is determined by striatal melanocortin 4 receptors
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2018 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 128, no 7, p. 3160-3170Article in journal (Refereed) Published
Abstract [en]

It is critical for survival to assign positive or negative valence to salient stimuli in a correct manner. Accordingly, harmful stimuli and internal states characterized by perturbed homeostasis are accompanied by discomfort, unease, and aversion. Aversive signaling causes extensive suffering during chronic diseases, including inflammatory conditions, cancer, and depression. Here, we investigated the role of melanocortin 4 receptors (MC4Rs) in aversive processing using genetically modified mice and a behavioral test in which mice avoid an environment that they have learned to associate with aversive stimuli. In normal mice, robust aversions were induced by systemic inflammation, nausea, pain, and. opioid receptorinduced dysphoria. In sharp contrast, mice lacking MC4Rs displayed preference or indifference toward the aversive stimuli. The unusual flip from aversion to reward in mice lacking MC4Rs was dopamine dependent and associated with a change from decreased to increased activity of the dopamine system. The responses to aversive stimuli were normalized when MC4Rs were reexpressed on dopamine D1 receptor-expressing cells or in the striatum of mice otherwise lacking MC4Rs. Furthermore, activation of arcuate nucleus proopiomelanocortin neurons projecting to the ventral striatum increased the activity of striatal neurons in an MC4R-dependent manner and elicited aversion. Our findings demonstrate that melanocortin signaling through striatal MC4Rs is critical for assigning negative motivational valence to harmful stimuli.

Place, publisher, year, edition, pages
AMER SOC CLINICAL INVESTIGATION INC, 2018
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-149861 (URN)10.1172/JCI97854 (DOI)000437234600044 ()29911992 (PubMedID)
Note

Funding Agencies|European Research Council; Swedish Medical Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County Council of Ostergotland; National Institute on Drug Abuse Intramural Research Program [ZIA000069]; Lars Hiertas Minne Foundation

Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2018-08-20
Blomqvist, A. & Engblom, D. (2018). Neural Mechanisms of Inflammation-Induced Fever. The Neuroscientist, 24(4), 381-399
Open this publication in new window or tab >>Neural Mechanisms of Inflammation-Induced Fever
2018 (English)In: The Neuroscientist, ISSN 1073-8584, E-ISSN 1089-4098, Vol. 24, no 4, p. 381-399Article, review/survey (Refereed) Published
Abstract [en]

Fever is a common symptom of infectious and inflammatory disease. It is well-established that prostaglandin E-2 is the final mediator of fever, which by binding to its EP3 receptor subtype in the preoptic hypothalamus initiates thermogenesis. Here, we review the different hypotheses on how the presence of peripherally released pyrogenic substances can be signaled to the brain to elicit fever. We conclude that there is unequivocal evidence for a humoral signaling pathway by which proinflammatory cytokines, through their binding to receptors on brain endothelial cells, evoke fever by eliciting prostaglandin E-2 synthesis in these cells. The evidence for a role for other signaling routes for fever, such as signaling via circumventricular organs and peripheral nerves, as well as transfer into the brain of peripherally synthesized prostaglandin E-2 are yet far from conclusive. We also review the efferent limb of the pyrogenic pathways. We conclude that it is well established that prostaglandin E-2 binding in the preoptic hypothalamus produces fever by disinhibition of presympathetic neurons in the brain stem, but there is yet little understanding of the mechanisms by which factors such as nutritional status and ambient temperature shape the response to the peripheral immune challenge.

Place, publisher, year, edition, pages
Sage Publications, 2018
Keywords
fever; cytokines; prostaglandin E2; brain endothelial cells; median preoptic nucleus; EP3 receptors
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-150242 (URN)10.1177/1073858418760481 (DOI)000439623500009 ()29557255 (PubMedID)2-s2.0-85044398777 (Scopus ID)
Note

Funding Agencies|Swedish Medical Research Council [07879, 20725]; European Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland

Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-09-07Bibliographically approved
Mirrasekhian, E., Nilsson, J. L. Å., Shionoya, K., Blomgren, A., Zygmunt, P. M., Engblom, D., . . . Blomqvist, A. (2018). The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1–mediated hypothermia and is associated with prostaglandin inhibition in the brain. The FASEB Journal
Open this publication in new window or tab >>The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1–mediated hypothermia and is associated with prostaglandin inhibition in the brain
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2018 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860Article in journal (Refereed) Published
Abstract [en]

The mode of action of paracetamol (acetaminophen), which is widely used for treating pain and fever, has remained obscure, but may involve several distinct mechanisms, including cyclooxygenase inhibition and transient receptor potential ankyrin 1 (TRPA1) channel activation, the latter being recently associated with paracetamol?s propensity to elicit hypothermia at higher doses. Here, we examined whether the antipyretic effect of paracetamol was due to TRPA1 activation or cyclooxygenase inhibition. Treatment of wild-type and TRPA1 knockout mice rendered febrile by immune challenge with LPS with a dose of paracetamol that did not produce hypothermia (150 mg/kg) but is known to be analgetic, abolished fever in both genotypes. Paracetamol completely suppressed the LPS-induced elevation of prostaglandin E2 in the brain and also reduced the levels of several other prostanoids. The hypothermia induced by paracetamol was abolished in mice treated with the electrophile-scavenger N-acetyl cysteine. We conclude that paracetamol?s antipyretic effect in mice is dependent on inhibition of cyclooxygenase activity, including the formation of pyrogenic prostaglandin E2, whereas paracetamol-induced hypothermia likely is mediated by the activation of TRPA1 by electrophilic metabolites of paracetamol, similar to its analgesic effect in some experimental paradigms.?Mirrasekhian, E., Nilsson, J. L. Å., Shionoya, K., Blomgren, A., Zygmunt, P. M., Engblom, D., Högestätt, E. D., Blomqvist, A. The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1?mediated hypothermia and is associated with prostaglandin inhibition in the brain.

Place, publisher, year, edition, pages
Federation of American Societies for Experimental Biology, 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-148562 (URN)10.1096/fj.201800272R (DOI)000447972500045 ()29738273 (PubMedID)
Note

Funding agencies: Swedish Medical Research Council [20725, 07879, 2014-3801]; European Research Council (ERC) Starting Grant; Knut and Alice Wallenberg Foundation; Swedish Brain Foundation; Swedish Cancer Foundation [16/0572]; County Council of Ostergotland; Medical Facult

Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-11-09Bibliographically approved
Nilsson, A., Wilhelms, D., Mirrasekhian, E., Jaarola, M., Blomqvist, A. & Engblom, D. (2017). Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.. Brain, behavior, and immunity, 61, 236-243, Article ID S0889-1591(16)30549-9.
Open this publication in new window or tab >>Inflammation-induced anorexia and fever are elicited by distinct prostaglandin dependent mechanisms, whereas conditioned taste aversion is prostaglandin independent.
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2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 236-243, article id S0889-1591(16)30549-9Article in journal (Refereed) Published
Abstract [en]

Systemic inflammation evokes an array of brain-mediated responses including fever, anorexia and taste aversion. Both fever and anorexia are prostaglandin dependent but it has been unclear if the cell-type that synthesizes the critical prostaglandins is the same. Here we show that pharmacological inhibition or genetic deletion of cyclooxygenase (COX)-2, but not of COX-1, attenuates inflammation-induced anorexia. Mice with deletions of COX-2 selectively in brain endothelial cells displayed attenuated fever, as demonstrated previously, but intact anorexia in response to peripherally injected lipopolysaccharide (10μg/kg). Whereas intracerebroventricular injection of a cyclooxygenase inhibitor markedly reduced anorexia, deletion of COX-2 selectively in neural cells, in myeloid cells or in both brain endothelial and neural cells had no effect on LPS-induced anorexia. In addition, COX-2 in myeloid and neural cells was dispensable for the fever response. Inflammation-induced conditioned taste aversion did not involve prostaglandin signaling at all. These findings collectively show that anorexia, fever and taste aversion are triggered by distinct routes of immune-to-brain signaling.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Anorexia, Conditioned place aversion, Cyclooxygenase, Fever, Inflammation, Lipopolysaccharide
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-136127 (URN)10.1016/j.bbi.2016.12.007 (DOI)000395365900026 ()27940259 (PubMedID)
Note

Funding agencies: Swedish Medical Research Council [20725, 07879]; European Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland

Available from: 2017-03-28 Created: 2017-03-28 Last updated: 2018-05-02Bibliographically approved
Matsuwaki, T., Shionoya, K., Ihnatko, R., Eskilsson, A., Kakuta, S., Dufour, S., . . . Blomqvist, A. (2017). Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses. Brain, behavior, and immunity, 66, 165-176
Open this publication in new window or tab >>Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses
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2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 66, p. 165-176Article in journal (Refereed) Published
Abstract [en]

Sickness responses to lipopolysaccharide (LPS) were examined in mice with deletion of the interleukin (IL)-1 type 1 receptor (IL-1R1). IL-1R1 knockout (1(0) mice displayed intact anorexia and HPA-axis activation to intraperitoneally injected LPS (anorexia: 10 or 120 mu g/kg; HPA-axis: 120 mu g/kg), but showed attenuated but not extinguished fever (120 g/kg). Brain PGE2 synthesis was attenuated, but Cox-2 induction remained intact. Neither the tumor necrosis factor-alpha (TNF alpha) inhibitor etanercept nor the IL -6 receptor antibody tocilizumab abolished the LPS induced fever in IL -1R1 KO mice. Deletion of IL -1R1 specifically in brain endothelial cells attenuated the LPS induced fever, but only during the late, 3rd phase of fever, whereas deletion of IL-1R1 on neural cells or on peripheral nerves had little or no effect on the febrile response. We conclude that while IL-1 signaling is not critical for LPS induced anorexia or stress hormone release, IL-1R1, expressed on brain endothelial cells, contributes to the febrile response to LPS. However, also in the absence of IL-1R1, LPS evokes a febrile response, although this is attenuated. This remaining fever seems not to be mediated by IL-6 receptors or TNFa, but by some yet unidentified pyrogenic factor. 

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Interleukin-1 type 1 receptor; Lipopolysaccharide; Fever; Anorexia; ACTH; Corticosterone; Endothelial cells; THF alpha; Interleukin-6; PGE(2)
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-143084 (URN)10.1016/j.bbi.2017.06.013 (DOI)000414236600018 ()28655587 (PubMedID)
Note

Funding Agencies|Japan Society for the Promotion of Science [15K18800]; Swedish Research Council [20725, 07879]; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland; Sixth Research Framework Programme of the European Union, Project MUGEN [MUGEN LSHG-CT-2005-005203]; MRC research grant [G0801296]

Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2018-06-18
Nilsson, A., Elander, L., Hallbeck, M., Örtegren (Kugelberg), U., Engblom, D. & Blomqvist, A. (2017). The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent. Brain, behavior, and immunity, 60, 27-31
Open this publication in new window or tab >>The involvement of prostaglandin E2 in interleukin-1β evoked anorexia is strain dependent
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2017 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 60, p. 27-31Article in journal (Refereed) Published
Abstract [en]

From experiments in mice in which the prostaglandin E2 (PGE2) synthesizing enzyme mPGES-1 was genetically deleted, as well as from experiments in which PGE2 was injected directly into the brain, PGE2 has been implicated as a mediator of inflammatory induced anorexia. Here we aimed at examining which PGE2 receptor (EP1–4) that was critical for the anorexic response to peripherally injected interleukin-1β (IL-1β). However, deletion of neither EP receptor in mice, either globally (for EP1, EP2, and EP3) or selectively in the nervous system (EP4), had any effect on the IL-1β induced anorexia. Because these mice were all on a C57BL/6 background, whereas previous observations demonstrating a role for induced PGE2 in IL-1β evoked anorexia had been carried out on mice on a DBA/1 background, we examined the anorexic response to IL-1β in mice with deletion of mPGES-1 on a C57BL/6 background and a DBA/1 background, respectively. We confirmed previous findings that mPGES-1 knock-out mice on a DBA/1 background displayed attenuated anorexia to IL-1β; however, mice on a C57BL/6 background showed the same profound anorexia as wild type mice when carrying deletion of mPGES-1, while displaying almost normal food intake after pretreatment with a cyclooxygenase-2 inhibitor. We conclude that the involvement of induced PGE2 in IL-1β evoked anorexia is strain dependent and we suggest that different routes that probably involve distinct prostanoids exist by which inflammatory stimuli may evoke an anorexic response and that these routes may be of different importance in different strains of mice.

Place, publisher, year, edition, pages
Academic Press, 2017
Keywords
Anorexia, Prostaglandin E2, EP receptors, Interleukin-1, Cyclooxygenase-2, Mice
National Category
Immunology Cell Biology Pharmacology and Toxicology
Identifiers
urn:nbn:se:liu:diva-132639 (URN)10.1016/j.bbi.2016.06.014 (DOI)000391908200004 ()27375005 (PubMedID)
Note

Funding agencies: Swedish Research Council [07879, 20725]; Swedish Cancer Foundation [213/692]; County Council of Ostergotland; Knut and Alice Wallenberg Foundation

Available from: 2016-11-18 Created: 2016-11-18 Last updated: 2018-05-02Bibliographically approved
Fritz, M., Klawonn, A., Nilsson, A., Kumar Singh, A., Zajdel, J., Wilhelms, D., . . . Engblom, D. (2016). Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice. Journal of Clinical Investigation, 126(2), 695-705
Open this publication in new window or tab >>Prostaglandin-dependent modulation of dopaminergic neurotransmission elicits inflammation-induced aversion in mice
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2016 (English)In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 126, no 2, p. 695-705Article in journal (Refereed) Published
Abstract [en]

Systemic inflammation causes malaise and general feelings of discomfort. This fundamental aspect of the sickness response reduces the quality of life for people suffering from chronic inflammatory diseases and is a nuisance during mild infections like common colds or the flu. To investigate how inflammation is perceived as unpleasant and causes negative affect, we used a behavioral test in which mice avoid an environment that they have learned to associate with inflammation-induced discomfort. Using a combination of cell-type-specific gene deletions, pharmacology, and chemogenetics, we found that systemic inflammation triggered aversion through MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E-2 (PGE(2)) synthesis. Further, we showed that inflammation-induced PGE(2) targeted EP1 receptors on striatal dopamine D1 receptor-expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, we demonstrated that inflammation-induced aversion was not an indirect consequence of fever or anorexia but that it constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE(2)-mediated modulation of the dopaminergic motivational circuitry is a key mechanism underlying the negative affect induced by inflammation.

Place, publisher, year, edition, pages
AMER SOC CLINICAL INVESTIGATION INC, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-126263 (URN)10.1172/JCI83844 (DOI)000370677300029 ()26690700 (PubMedID)
Note

Funding Agencies|European Research Council (ERC); Swedish Medical Research Council; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; County Council of Ostergotland; Swedish Cancer Foundation; Veterans Administration Merit award; NIH [NS33987, NS72337]

Available from: 2016-03-21 Created: 2016-03-21 Last updated: 2019-04-29Bibliographically approved
Vasilache, A.-M., Qian, H. & Blomqvist, A. (2015). Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E2 signaling. Brain, behavior, and immunity, 48, 31-41
Open this publication in new window or tab >>Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E2 signaling
2015 (English)In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 48, p. 31-41Article in journal (Refereed) Published
Abstract [en]

The cells constituting the blood-brain barrier are critical for the transduction of peripheral immune signals to the brain, but hitherto no comprehensive analysis of the signaling events that occur in these cells in response to a peripheral inflammatory stimulus has been performed. Here, we examined the inflammatory transcriptome in blood-brain barrier cells, including endothelial cells, pericytes, and perivascular macrophages, which were isolated by fluorescent-activated cell sorting, from non-immune-challenged mice and from mice stimulated by bacterial wall lipopolysaccharide. We show that endothelial cells and perivascular macrophages display distinct transcription profiles for inflammatory signaling and respond in distinct and often opposing ways to the immune stimulus. Thus, endothelial cells show induced PGE2 synthesis and transport with attenuation of PGE2 catabolism, increased expression of cytokine receptors and down-stream signaling molecules, and downregulation of adhesion molecules. In contrast, perivascular macrophages show downregulation of the synthesis of prostanoids other than PGE2 and of prostaglandin catabolism, but upregulation of interleukin-6 synthesis. Pericytes were largely unresponsive to the immune stimulation, with the exception of downregulation of proteins involved in pericyte-endothelial cell communication. While the endothelial cells account for most of the immune-induced gene expression changes in the blood-brain barrier, the response of the endothelial cells occurs in a concerted manner with that of the perivascular cells to elevate intracerebral levels of PGE2, hence emphasizing the critical role of PGE2 in immune-induced signal transduction across the blood-brain barrier.

Place, publisher, year, edition, pages
Academic Press, 2015
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-114377 (URN)10.1016/j.bbi.2015.02.003 (DOI)000358460700005 ()25678162 (PubMedID)
Note

This work was supported by Grants from the Swedish Research Council (07879 to AB, and 22241 to HQ), the Swedish Cancer Foundation (13 0295 to AB), the Swedish Brain Foundation (to AB), the County Council of Ostergotland (to AMV), and Knut och Alice Wallenberg Foundation (WIRM to HQ).

Available from: 2015-02-19 Created: 2015-02-19 Last updated: 2018-01-11Bibliographically approved
Okuda, D. T., Melmed, K., Matsuwaki, T., Blomqvist, A. & Craig, A. D. (2014). Central neuropathic pain in MS is due to distinct thoracic spinal cord lesions.. Annals of clinical and translational neurology, 1(8), 554-61
Open this publication in new window or tab >>Central neuropathic pain in MS is due to distinct thoracic spinal cord lesions.
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2014 (English)In: Annals of clinical and translational neurology, ISSN 2328-9503, Vol. 1, no 8, p. 554-61Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To determine a neuro-anatomic cause for central neuropathic pain (CNP) observed in multiple sclerosis (MS) patients.

METHODS: Parallel clinical and neuro-anatomical studies were performed. A clinical investigation of consecutively acquired MS patients with and without CNP (i.e. cold allodynia or deep hyperesthesia) within a single MS center was pursued. A multivariate logistic regression model was used to assess the relationship between an upper central thoracic spinal cord focus to central pain complaints. To identify the hypothesized autonomic interneurons with bilateral descending projections to lumbosacral sensory neurons, retrograde single- and double-labeling experiments with CTb and fluorescent tracers were performed in three animal species (i.e. rat, cat, and monkey).

RESULTS: Clinical data were available in MS patients with (n = 32; F:23; median age: 34.6 years (interquartile range [IQR]: 27.4-45.5)) and without (n = 30; F:22; median age: 36.6 years [IQR: 31.6-47.1]) CNP. The value of a central focus between T1-T6 in relation to CNP demonstrated a sensitivity of 96.9% (95% confidence interval [CI]: 83.8-99.9) and specificity of 83.3% (95% CI: 65.3-94.4). A significant relationship between CNP and a centrally located focus within the thoracic spine was also observed (odds ratio [OR]: 155.0 [95% CI lower limit: 16.0]; P < 0.0001, two-tailed Fisher exact test). In all animal models, neurons with bilateral descending projections to the lumbosacral superficial dorsal horn were concentrated in the autonomic intermediomedial nucleus surrounding the mid-thoracic central canal.

INTERPRETATION: Our observations provide the first evidence for the etiology of CNP. These data may assist with the development of refined symptomatic therapies and allow for insights into unique pain syndromes observed in other demyelinating subtypes.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
National Category
Clinical Medicine Neurosciences
Identifiers
urn:nbn:se:liu:diva-115268 (URN)10.1002/acn3.85 (DOI)000209815300004 ()25356427 (PubMedID)
Available from: 2015-03-11 Created: 2015-03-11 Last updated: 2018-01-11Bibliographically approved
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