Acute peripheral inflammation induces moderate glial activation and spinal IL-1β expression that correlates with pain behavior in the rat

Sweitzer, Sarah M.; Colburn, Raymond W.; Rutkowski, Maria D.; DeLeo, Joyce A.

doi:10.1016/s0006-8993(99)01326-8

Cited by 306 publications

(210 citation statements)

References 29 publications

Supporting

Mentioning

186

Contrasting

Unclassified

Order By: Relevance

“…These phenotype changes seem to involve receptor (e.g., VR-1) upregulation and thus seem to be distinct from the acute heat sensitization observed in the present in vitro study. Interestingly, similar long-term effects also are known for IL-1␤ and TNF-␣ (Sommer et al, 1998(Sommer et al, , 1999Sweitzer et al, 1999). The acute effects presented here, however, reveal a dual role for proinflammatory cytokines: on one hand they induce sensitization in the acute phase of inflammation possibly via receptor associated kinases and phosphorylation of ion channels, whereas on the other hand hyperalgesia is maintained in chronic inflammation by upregulation of receptors and secondary signaling mechanisms.…”

Section: Discussionsupporting

confidence: 65%

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

2000

View full text Add to dashboard Cite

Proinflammatory cytokines contribute to the development of inflammatory and neuropathic pain and hyperalgesia in many in vivo models. The rat skin model was used to investigate the effects of proinflammatory cytokines on the basal and heatevoked release of calcitonin gene-related peptide from nociceptors in vitro. In contrast to the excitatory effects of cytokines observed in vivo, none of the cytokines tested evoked any calcitonin gene-related peptide (CGRP) release at normal skin temperature of 32°C. However, the cytokines IL-1␤, tumor necrosis factor (TNF)-␣, and IL-6 but not IL-8 induced a pronounced and transient sensitization of the heat-evoked CGRP release from nociceptors in vitro. This heat sensitization was dose dependent, with EC 50 for IL-1␤ of 2.7 ng/ml and for TNF-␣ of 3.1 ng/ml. The maximum IL-1␤ effect reached almost 600% of the heat-evoked release, and the maximum TNF-␣ effect induced a rise in CGRP release of 350%. In contrast to IL-1␤ and TNF-␣, IL-6 did not induce heat sensitization when applied alone but was only effective in the presence of soluble IL-6 receptor. This suggests a constitutive expression of signaling receptors for TNF and IL-1␤ and the signal transduction molecule gp130 but not IL-6 receptor or IL-8 receptor. Furthermore, the acute cytokine signaling observed in the present study was independent of transcriptional pathways because sensitization occurred on short latency in vitro and under conditions that excluded chemotactic accumulation of immune cells from blood vessels. Our results demonstrate that interleukins may play an important role in the initiation of heat hyperalgesia in inflammation and neuropathy.

show abstract

Section: Discussionsupporting

confidence: 65%

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

2000

View full text Add to dashboard Cite

show abstract

“…Upregulation of OX-42 or Iba1 is indicative of microglia activation. In inflammatory pain models that do not involve nerve injury, such as carrageenan model (Hua et al, 2005) and zymosan model (Clark et al, 2007a;Sweitzer et al, 1999), there is only a very moderate increase of OX42-immunoreactivity (IR) in the spinal cord. Whereas other models such as complete Freund's adjuvant model (Clark et al, 2007a;Zhang et al, 2003) and mustard oil model (Molander et al, 1997) fail to demonstrate any increase of OX-42-IR.…”

Section: Microglia Activation and Proliferation In The Spinal Cord Inmentioning

confidence: 99%

“…Whereas other models such as complete Freund's adjuvant model (Clark et al, 2007a;Zhang et al, 2003) and mustard oil model (Molander et al, 1997) fail to demonstrate any increase of OX-42-IR. The inflammatory pain model that shows significant OX-42 increase is the formalin model (Aumeerally et al, 2004;Fu et al, 1999;Fu et al, 2000;Sweitzer et al, 1999). But formalin injection into a hindpaw will also produce nerve injury in the peripheral axons.…”

Section: Microglia Activation and Proliferation In The Spinal Cord Inmentioning

confidence: 99%

Do glial cells control pain?

Wen²,

et al. 2007

View full text Add to dashboard Cite

Management of chronic pain is a real challenge, and current treatments focusing on blocking neurotransmission in the pain pathway have only resulted in limited success. Activation of glia cells has been widely implicated in neuroinflammation in the central nervous system, leading to neruodegeneration in many disease conditions such as Alzheimer's and multiple sclerosis. The inflammatory mediators released by activated glial cells, such as tumor necrosis factor-α and interleukin-1β can not only cause neurodegeneration in these disease conditions, but also cause abnormal pain by acting on spinal cord dorsal horn neurons in injury conditions. Pain can also be potentiated by growth factors such as BDNF and bFGF that are produced by glia to protect neurons. Thus, glia cells can powerfully control pain when they are activated to produce various pain mediators. We will review accumulating evidence supporting an important role of microglia cells in the spinal cord for pain control under injury conditions (e.g. nerve injury). We will also discuss possible signaling mechanisms in particular MAP kinase pathways that are critical for glia control of pain. Investigating signaling mechanisms in microglia may lead to more effective management of devastating chronic pain.

show abstract

“…Glial cell proliferation in the dorsal horn induced either by diseases or physical trauma of peripheral nerves has recently become into attention because of the possibility of the glial involvement in naturopathic pain. Both infl ammation 1,[3][4][5][6][7][8][9][10][11][12][13][14][15] and nerve injury 16 are able to activate glial cells in the dorsal horn of the spinal cord, which have been related to development and maintenance of persistent pain states 15,17 .Like the astroglia, which respond in the central nervous system after central or peripheral axotomy, Schwann cells, a type of glia encountered in the peripheral nervous system, which form myelin sheet of nerve axons, are also capable to become reactive after axotomy of peripheral nerves 8,18 . Activated SC are also able to release neurotrophic factors contributing to protect and to stimulate neuronal regeneration 8 .…”

Section: Introductionmentioning

confidence: 99%

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

Dallo¹,

Reichert²,

Júnior³

et al. 2007

Acta Cir. Bras.

View full text Add to dashboard Cite

Differential astroglial responses in the spinal cord of rats -ORIGINAL ARTICLE NeuroregenerationDifferential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract. Implications on cell therapy for nerve repair 1 Respostas astrocitárias na medula espinal do rato submetido ao esmagamento duplo do nervo ciático e tratado com injeção local de suspensão de células de Schwann cultivadas ou de extrato de medula espinal lesada. Implicações na terapia celular para o reparo do nervo ABSTRACT Purpose: Reactive astrocytes are implicated in several mechanisms after central or peripheral nervous system lesion, including neuroprotection, neuronal sprouting, neurotransmission and neuropathic pain. Schwann cells (SC), a peripheral glia, also react after nerve lesion favoring wound/repair, fi ber outgrowth and neuronal regeneration. We investigated herein whether cell therapy for repair of lesioned sciatic nerve may change the pattern of astroglial activation in the spinal cord ventral or dorsal horn of the rat. Methods: Injections of a cultured SC suspension or a lesioned spinal cord homogenized extract were made in a reservoir promoted by a contiguous double crush of the rat sciatic nerve. Local injection of phosphate buffered saline (PBS) served as control. One week later, rats were euthanized and spinal cord astrocytes were labeled by immunohistochemistry and quantifi ed by means of quantitative image analysis. Results: In the ipsilateral ventral horn, slight astroglial activations were seen after PBS or SC injections, however, a substantial activation was achieved after cord extract injection in the sciatic nerve reservoir. Moreover, SC suspension and cord extract injections were able to promote astroglial reaction in the spinal cord dorsal horn bilaterally. Conclusion: Spinal cord astrocytes react according to repair processes of axotomized nerve, which may infl uence the functional outcome. The event should be considered during the neurosurgery strategies. Key words: Sciatic nerve lesion. Astrocyte. Neuronal protection. Neuroplasticity. Neuroregeneration. Pain. Review. RESUMOObjetivo: Astrócitos reativos participam de vários mecanismos após lesões do sistema nervoso central e periférico, os quais incluem neuroproteção, brotamento neuronal, neurotransmissão e dor neuropática. As células de Schwann (CS), um tipo de glia periférica, também reagem com a lesão do nervo, podendo interferir com o reparo e cicatrização, crescimento de fi bras e regeneração neuronais. Investigamos aqui a possibilidade da terapia celular para o reparo do nervo ciático poder alterar o padrão da ativação astrocitária nos cornos anterior e posterior da medula espinal do rato. Métodos: Suspensão de CS cultivadas ou extrato homogeneizado de medula espinal lesada de rato foram inoculados num reservatório feito a partir de dois esmagamentos aplicados no nervo ciático do rato distantes 0,5mm entre si. Injeção local de salina t...

show abstract

Acute peripheral inflammation induces moderate glial activation and spinal IL-1β expression that correlates with pain behavior in the rat

Cited by 306 publications

References 29 publications

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Do glial cells control pain?

Differential astroglial responses in the spinal cord of rats submitted to a sciatic nerve double crush treated with local injection of cultured Schwann cell suspension or lesioned spinal cord extract: implications on cell therapy for nerve repair

Contact Info

Product

Resources

About