Interleukin-1β increases spinal cord wind-up activity in normal but not in monoarthritic rats

Constandil, Luís; Soto-Moyano, Rubén; Mondaca, Mauricio; Sáez, Hernán; Laurido, Claudio; Muñoz, Carlos; López, Nandy; Hernández, Alejandro

doi:10.1016/s0304-3940(03)00278-7

Cited by 15 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further support to this idea is provided by studies showing that intrathecal administration of IL-1β in healthy rodents induces hyperalgesia and allodynia [16–21, 89] and enhance both the acute response to C-fiber stimulation and the wind-up activity of dorsal horn neurons [15, 22]. IL-1β is reported to be upregulated in the spinal cord during inflammatory [4, 6, 7, 23] and neuropathic pain [11, 12] which led to the notion that IL-1β can be an important contributor to the development of persistent pain states [7, 9, 21, 28].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Holló

Ducza

Hegyi

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

Background: All known biological functions of the pro-inflammatory cytokine interleukin-1β (IL-1β) are mediated by type 1 interleukin receptor (IL-1R1). IL-1β-IL-1R1 signaling modulates various neuronal functions including spinal pain processing. Although the role of IL-1β in pain processing is generally accepted, there is a discussion in the literature whether IL-1β exerts its effect on spinal pain processing by activating neuronal or glial IL-1R1. To contribute to this debate, here we investigated the expression and cellular distribution of IL-1R1 in the superficial spinal dorsal horn in control animals and also in inflammatory pain. Methods: Experiments were performed on rats and wild type as well as IL-1R1-deficient mice. Inflammatory pain was evoked by unilateral intraplantar injection of complete Freund adjuvant (CFA). The nociceptive responsiveness of control and CFA-treated animals were tested daily for withdrawal responses to mechanical and thermal stimuli before and after CFA injection. Changes in the expression of 48 selected genes/mRNAs and in the quantity of IL-1R1 protein during the first 3 days after CFA injection were measured with the TaqMan low-density array method and Western blot analysis, respectively. The cellular localization of IL-1R1 protein was investigated with single and double staining immunocytochemical methods.

show abstract

Section: Discussionmentioning

confidence: 99%

Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Holló

Ducza

Hegyi

et al. 2017

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…Neurones express receptors for proinflammatory cytokines and proinflammatory cytokines increase the excitability and 'windup' of dorsal horn neurones that respond to painful stimuli [119,120]. In addition, proinflammatory cytokines and as-yet unidentified 70 kDa products of activated microglia can exert indirect effects on nociceptive neuronal function, such as potentiating the efficacy of N-methyl-d-aspartate (NMDA) channel openings [121,122].…”

Section: Immune Activation Can Alter the Function Of Drg And Spinal Nmentioning

confidence: 99%

Immune regulation of central nervous system functions: from sickness responses to pathological pain

Watkins

Maier

2005

Journal of Internal Medicine

321

231

View full text Add to dashboard Cite

Classically, the central nervous system (CNS) and the immune system are thought to operate independently of each other. This simplistic view has been corrected in recent years, first with the recognition that the brain dynamically modulates the immune system, and later with the reverse; that is, that the immune system modulates the CNS as well. The evidence that the immune system regulates CNS functions is first reviewed. This immune-to-brain communication pathway triggers the production of a constellation of CNS-mediated phenomena, collectively referred to as 'sickness responses'. These sickness responses are created by immune-to-brain signals activating CNS glia to release glial proinflammatory cytokines. The most recently recognized member of this constellation of changes is enhanced pain responsivity. The hypothesis is then developed that pathological, chronic pain may result from 'tapping into' this ancient survival-oriented circuitry, including the activation of immune and glial cells and the release of immune/glial proinflammatory cytokines. This can occur at the level of peripheral nerves, dorsal root ganglia, spinal cord, and likely at higher brain areas. The implications of this model for human chronic pain syndromes and clinical resolution of these chronic pain states are then discussed.

show abstract

“…It is accepted that cytokines have a role as neuromodulators in the central nervous system, specifically at the level of second-order nociceptive neurons. In this regard, it has been reported that IL-1β is able to increase the C-fiber response and windup activity in the spinal cord [18] at the level of nociceptive afferent terminals, where IL-1β increases the release of substance P and glutamate [19]. …”

Section: Introductionmentioning

confidence: 99%

Antinociceptive interaction of (±)-CPP and propentofylline in monoarthritic rats

et al. 2012

Self Cite

View full text Add to dashboard Cite

IntroductionMultiple studies have shown that glial cells of the spinal cord, such as astrocytes and microglia, have close contact with neurons, suggesting the term tripartite synapse. In these synapses, astrocytes surrounding neurons contribute to neuronal excitability and synaptic transmission, thereby increasing nociception and thus the persistence of chronic pain. Conversely, the N-methyl-D-aspartate (NMDA) receptor is crucial in the generation and maintenance of chronic pain. It has multiple sites of modulation. One is the site of recognition of extracellular neurotransmitter (glutamate), which can be blocked by competitive antagonists such as (3-(2-carboxipiperazin-4)1-propyl phosphonic acid), (±)-CPP, resulting in a blockade of the calcium current and thus the intracellular transduction process. In the present study, we investigated whether the potential antinociceptive effect of glial inhibition produced by propentofylline (PPF) can be enhanced when combined with an NMDA-receptor inhibitor such as (±)-CPP.MethodsWe used Sprague-Dawley monoarthritic rats. The monoarthritis was induced by injection of complete Freund adjuvant in the right tibiotarsal joint. Four weeks later, rats were treated with PPF (1, 10, 30, and 100 μg/10 μl) intrathecally (i.t.) for 10 days, injected once with (±)-CPP (2.5, 5, 12.5, 25, 50, and 100 μg/10 μl, i.t.), or both treatments combined. The antinociceptive effect was evaluated on day 11 for PPF and immediately to (±)-CPP, by assessing the vocalization threshold to mechanical stimulation of the arthritic paw.ResultsThe data indicate that intrathecal administration of increasing concentrations of (±)-CPP or PPF produced a significant dose-dependent antinociceptive effect with respect to monoarthritic rats receiving saline. The linear regression analysis showed that the dose that produces 30% of maximal effect (ED30) for i.t. (±)-CPP was 3.97 μg, and 1.42 μg for i.t. PPF. The administration of the PPF and (±)-CPP combination in fixed proportions of ED30 produced a dose-dependent antinociceptive effect, showing an interaction of the supraadditive type.ConclusionsThe results suggest that glia inhibitors can synergically potentiate the effect of glutamate blockers for the treatment of chronic inflammatory pain.

show abstract

Interleukin-1β increases spinal cord wind-up activity in normal but not in monoarthritic rats

Cited by 15 publications

References 19 publications

Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Interleukin-1 receptor type 1 is overexpressed in neurons but not in glial cells within the rat superficial spinal dorsal horn in complete Freund adjuvant-induced inflammatory pain

Immune regulation of central nervous system functions: from sickness responses to pathological pain

Antinociceptive interaction of (±)-CPP and propentofylline in monoarthritic rats

Contact Info

Product

Resources

About