Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats

Oka, Takahiro; Oka, Kae; Hosoi, Masako; Hori, Tetsuro

doi:10.1016/0006-8993(95)00691-i

Cited by 114 publications

(65 citation statements)

References 28 publications

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“…Generally there has been a trend of endogenous IL-6 having pro-nociceptive effects on exaggerated pain states as revealed by use of anti-IL-6 neutralizing antibodies (Arruda et al, 2000;Chacur et al, 2004;DeLeo et al, 1996;Milligan et al, 2003); present study) and exogenous IL-6 having anti-nociceptive effects as revealed by administration of IL-6 protein (Choi et al, 2003;Flatters et al, 2003). However, three studies using exogenous IL-6 did report pro-nociceptive effects (DeLeo et al, 1996;Oka et al, 1995;Vissers et al, 2005). Comparison of the dosages between these studies does not indicate that these differences in effects are seen because of low vs. high drug doses, as these studies used several different drug doses.…”

Section: Discussionmentioning

confidence: 51%

“…In terms of its pro-nociceptive effects beyond the present study, intracerebroventricular injection of IL-6 induced thermal hyperalgesia in naïve rats (Oka et al, 1995), intrathecal injection of IL-6 induced touch-evoked allodynia in naïve rats (DeLeo et al, 1996), thermal hyperalgesia in rats with a sciatic nerve lesion (DeLeo et al, 1996), and increased cold allodynia in neuropathic rats (Vissers et al, 2005). In addition, an anti-IL-6 antibody blocked or attenuated the mechanical allodynia induced by peripheral nerve trauma (Arruda et al, 2000) or peripheral nerve inflammation (Chacur et al, 2004;Milligan et al, 2003), and CCI-induced cold allodynia (Vissers et al, 2005).…”

Section: Discussionmentioning

confidence: 58%

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Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal HIV-1 envelope glycoprotein gp120

Schoeniger-Skinner

Ledeboer

Frank

et al. 2007

Brain, Behavior, and Immunity

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Spinal cord glia (microglia and astrocytes) contribute to enhanced pain states. One model that has been used to study this phenomenon is intrathecal (i.t.) administration of gp120, an envelope glycoprotein of HIV-1 known to activate spinal cord glia and thereby induce low-threshold mechanical allodynia, a pain symptom where normally innocuous (non-painful) stimuli are perceived as painful. Previous studies have shown that i.t. gp120-induced allodynia is mediated via the release of the glial pro-inflammatory cytokines, tumor necrosis factor-α (TNF), and interleukin-1β (IL-1). As we have recently reported that i.t. gp120 induces the release of interleukin-6 (IL-6), in addition to IL-1 and TNF, the present study tested whether this IL-6 release in spinal cord contributes to gp120-induced mechanical allodynia and/or to gp120-induced increases in TNF and IL-1. An i.t. anti-rat IL-6 neutralizing antibody was used to block IL-6 actions upon its release by i.t. gp120. This IL-6 blockade abolished gp120-induced mechanical allodynia. While the literature predominantly documents the cascade of pro-inflammatory cytokines as beginning with TNF, followed by the stimulation of IL-1, and finally TNF plus IL-1 stimulating the release of IL-6, the present findings indicate that a blockade of IL-6 inhibits the gp120-induced elevations of TNF, IL-1, and IL-6 mRNA in dorsal spinal cord, elevation of IL-1 protein in lumbar dorsal spinal cord, and TNF and IL-1 protein release into the surrounding lumbosacral cerebrospinal fluid. These results would suggest that IL-6 induces pain facilitation, and may do so in part by stimulating the production and release of other proinflammatory cytokines.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 58%

Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal HIV-1 envelope glycoprotein gp120

Schoeniger-Skinner

Ledeboer

Frank

et al. 2007

Brain, Behavior, and Immunity

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“…Cohen et al [4] demonstrated, using northern analysis, that treatment of various cell lines with IL-6 for 6-48 h resulted in a significant induction of vascular endothelial growth factor (VEGF) mRNA. It has been reported that IL-6 also interferes with pain sensation in rats; for instance, intracerebro-ventricular injection of IL-6 induces thermal hyperalgesia [15]. In line with this finding is the observation that intrathecal IL-6 production results in allodynia and thermal hyperalgesia following peripheral nerve injury [6].…”

Section: Fibronectinmentioning

confidence: 75%

Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine

et al. 2002

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IntroductionThe pathogenetic mechanism of low back pain and nerve root damage in lumbar disc herniation is the subject of ongoing debate. In particular, given that the mechanicalischaemic hypothesis alone cannot explain the cause-effect relationship between disc degeneration and neurological impairment, a biochemical mechanism is likely to be involved. It has recently been demonstrated that the autologous nucleus pulposus can induce histological and functional changes in spinal nerve roots when applied epidurally [17]. Cells of the nucleus pulposus can produce prostaglandin E2, interleukin-1 and interleukin-6 (IL-6) [31], phospholipase A2 [26], and growth factors like fibroblast-like growth factor (FGF) [32] and insulin-like growth factor-1 (IGF-1) [18]. These factors are known to control cell metabolism and to promote inflammatory processes. Moreover, recent studies suggest a critical role for IL-6 and its receptor in the modulation of pain [8]. The mechanisms of action underlying the possible effect of these factors on spinal nerve root structure and function are, however, still unknown. In addition, the fact that nerve roots differ from peripheral nerves in their anatomical, biomechanical, and physiological properties prevents extrapolation from the extensive literature and the numerous experimental models of peripheral nerve compression to the pathophysiology of root injury [5,23,25]. The working hypothesis of the present study is that transforming growth factor-β1 (TGF-β1), IGF-1, IL-6 and IL-6-receptor (IL-6R) can be produced at the site of herniation. This hypothesis was immunohistochemically explored by analysing normal and protruded intervertebral disc tissue for these factors.Abstract Nerve root irritation induced by factors produced by the intervertebral disc may play a crucial role in the pathophysiology of sciatic pain production. In this study we used immunohistochemistry to investigate the presence of transforming growth factor-β1 (TGF-β1), insulinlike growth factor-1 (IGF-1), interleukin-6 (IL-6), IL-6-receptor (IL-6R) and fibronectin in lumbar disc bioptic specimens from 30 patients with disc herniation (protrusion type). Chondrocytes of herniated discs stained positive for TGF-β1, IGF-1, IL-6 and fibronectin. We demonstrated for the first time the presence of IL-6-R in the chondrocytes of herniated tissue. Specimens from autoptic healthy tissue were used as controls. In these sections no immunoreaction for TGF-β1, IL-6, or IL-6R was found, while they expressed IGF-1 and fibronectin, but in lower quantities than herniated discs. These results demonstrated the production of factors such as TGF-β1, IGF-1, IL-6, IL-6R and fibronectin at the site of lumbar disc herniation.

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“…A lesão do nervo isquiático promove aumento da expressão de IL-6 no local, assim como no corno dorsal da medula espinal e no gânglio da raiz dorsal 50 . Se injetada nos ventrículos laterais de ratos, a IL-6 induz hiperalgesia térmica 51 . Apesar de estudos controversos, em ratos que não produzem IL-6 há um retardo no desenvolvimento de alodinia mecânica após lesão de nervo periférico 52 .…”

Section: Citocinasunclassified

“…Lesions of the sciatic nerve promote the local increase in IL-6 expression, as well as in the dorsal horn of the spinal cord 50 . In mice, the injection of IL-6 in the lateral ventricles produces thermal hyperalgesia 51 . Des-pite controversial studies, in mice that do not produce IL-6 the development of mechanical allodynia after peripheral nerve lesion is delayed 52 .…”

Section: Cytokinesmentioning

confidence: 99%

Dor neuropática: aspectos neuroquímicos

Kraychete¹,

Gozzani²,

Kraychete³

2008

Rev. Bras. Anestesiol.

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Rev Bras AnestesiolARTIGO DE REVISÃO 2008; 58: 5: 492-505 REVIEW ARTICLE RESUMO Kraychete DC, Gozzani JL, Kraychete AC -Dor Neuropática -Aspectos Neuroquímicos. JUSTIFICATIVA E OBJETIVOS:A dor neuropática é causada por lesão ou inflamação do sistema nervoso. É síndrome complexa, com mecanismos biológicos pouco esclarecidos, envolvendo teorias inflamatórias e imunes. O objetivo desta revisão foi descrever os principais fatores biológicos relacionados com a dor neuropática, associando de forma lógica as hipóteses sugeridas pela literatura. CONTEÚDO:Foram descritos os principais neuromediadores, canais iônicos e células, incluindo as do sistema imune envolvidos na excitabilidade neuronal, assim como enfatizada possível seqüência de ativação ou interação desses agentes na alteração neuroplástica decorrente da agressão ao nervo.CONCLUSÕES: Do estudo, foi possível concluir que os avanços no conhecimento da fisiopatologia da dor neuropática podem determinar novos alvos para abordagem farmacológica dessa síndrome.Unitermos: DOR: neuropática; FISIOLOGIA: neurotransmissores. SUMMARYKraychete DC, Gozzani JL, Kraychete AC -Neuropathic PainNeurochemical Aspects. BACKGROUND AND OBJECTIVES:Neuropathic pain is caused by damage or inflammation of the nervous system. It is a complex syndrome and its biological mechanisms, involving inflammatory and immunologic theories, are not clear. The objective of this review was to describe the main biologic factors associated with neuropathic pain, making a logical association between hypotheses suggested in the literature. CONTENTS:The main neuromediators, ion channels, and cells, including cells in the nervous system involved in neuronal excitation are described, and the possible activation sequence or interaction among those agents in the neoplastic change secondary to nerve damage are emphasized. CONCLUSIONS:It was possible to conclude that the advances on the knowledge of the pathophysiology of neuropathic pain can determine new pharmacologic approaches for this syndrome.

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Intracerebroventricular injection of interleukin-6 induces thermal hyperalgesia in rats

Cited by 114 publications

References 28 publications

Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal HIV-1 envelope glycoprotein gp120

Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal HIV-1 envelope glycoprotein gp120

Cytokines and growth factors in the protruded intervertebral disc of the lumbar spine

Dor neuropática: aspectos neuroquímicos

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