Contralateral non-operated nerve to transected rat sciatic nerve shows increased expression of IL-1β, TGF-β1, TNF-α, and IL-10

Ruohonen, Saku; Jagodi, Maja; Khademi, Mohsen; Taskinen, Hanna‐Stiina; Ojala, Pekka; Olsson, Tomas; Röyttä, Matias

doi:10.1016/s0165-5728(02)00281-3

Cited by 55 publications

(24 citation statements)

References 39 publications

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“…In addition to the satellite cells, the DRG neurons, mainly those in contralateral side, displayed an increased immunofluorescence for TNF-α after the sciatic nerve transection. An increased immunostaining for TNF-α in the neurons of both ipsi-and contralateral L4-L5 DRG induced by the nerve transection is consistent with up-regulation of TNF-α in the injured and contralateral intact sciatic nerve (Ruohonen et al, 2002). Moreover, the sciatic nerve transection and subsequent repair enhanced cytokine expression (IL-1ß, TGF-ß1) in the contralateral DRG and promoted contralateral nerve regeneration in vivo by shortening the initial delay (Ryoke et al, 2000).…”

Section: Discussionsupporting

confidence: 68%

Intra- and Extraneuronal Changes of Immunofluorescence Staining for TNF- and TNFR1 in the Dorsal Root Ganglia of Rat Peripheral Neuropathic Pain Models

Dubový¹,

Jančálek

Klusáková³

et al. 2006

Cell Mol Neurobiol

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1. Several lines of evidence suggest that cytokines and their receptors are initiators of changes in the activity of dorsal root ganglia (DRG) neurons, but their cellular distribution is still very limited or controversial. Therefore, the goal of present study was to investigate immunohistochemical distribution of TNF-alpha and TNF receptor-1 (TNFR1) proteins in the rat DRG following three types of nerve injury. 2. The unilateral sciatic and spinal nerve ligation as well as the sciatic nerve transection were used to induce changes in the distribution of TNF-alpha and TNFR1 proteins. The TNF-alpha and TNFR1 immunofluorescence was assessed in the L4-L5 DRG affected by nerve injury for 1 and 2 weeks, and compared with the contralateral ones and those removed from naive or sham-operated rats. A part of the sections was incubated for simultaneous immunostaining for TNF-alpha and ED-1. The immunofluorescence brightness was measured by image analysis system (LUCIA-G v4.21) to quantify immunostaining for TNF-alpha and TNFR1 in the naive, ipsi- and contralateral DRG following nerve injury. 3. The ipsilateral L4-L5 DRG and their contralateral counterparts of the rats operated for nerve injury displayed an increased immunofluorescence (IF) for TNF-alpha and TNFR1 when compared with DRG harvested from naive or sham-operated rats. The TNFalpha IF was increased bilaterally in the satellite glial cells (SGC) and contralaterally in the neuronal nuclei following sciatic and spinal nerve ligature. The neuronal bodies and their SGC exhibited bilaterally enhanced IF for TNF-alpha after sciatic nerve transection for 1 and 2 weeks. In addition, the affected DRG were invaded by ED-1 positive macrophages which displayed simultaneously TNFalpha IF. The ED-1 positive macrophages were frequently located near the neuronal bodies to occupy a position of the satellites. 4. The sciatic and spinal nerve ligature resulted in an increased TNFR1 IF in the neuronal bodies of both ipsi- and contralateral DRG. The sciatic nerve ligature for 1 week induced a rise in TNFR1 IF in the contralateral DRG neurons and their SGC to a higher level than in the ipsilateral ones. In contrast, the sciatic nerve ligature for 2 weeks caused a similar increase of TNFR1 IF in the neurons and their SGC of both ipsi- and contralateral DRG. The spinal nerve ligature or sciatic nerve transection resulted in an increased TNFR1 IF located at the surface of the ipsilateral DRG neurons, but dispersed IF in the contralateral ones. In addition, the SGC of the contralateral in contrast to ipsilateral DRG displayed a higher TNFR1 IF. 5. Our results suggest more sources of TNF-alpha protein in the ipsilateral and contralateral DRG following unilateral nerve injury including macrophages, SGC and primary sensory neurons. In addition, the SGC and macrophages, which became to be satellites, are well positioned to regulate activity of the DRG neurons by production of TNF-alpha molecules. Moreover, the different cellular distribution of TNFR1 in the ipsi- and contralateral DRG may refle...

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Section: Discussionsupporting

confidence: 68%

Intra- and Extraneuronal Changes of Immunofluorescence Staining for TNF- and TNFR1 in the Dorsal Root Ganglia of Rat Peripheral Neuropathic Pain Models

Dubový¹,

Jančálek

Klusáková³

et al. 2006

Cell Mol Neurobiol

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“…Therefore, these results indicate a temporal dynamics for endogenous levels of IL-1β across supraspinal brain regions in animals with neuropathic pain. A similar time dependent change in IL-1β expression has been noted in the contralateral non-operated nerve following transection of sciatic nerve in the rat [26]. The authors observed high expression of IL-1β, as well as interleukin-10 and transforming growth factor-β1, in the endoneurium of intact sciatic nerve, which diminished to control levels at day 7, and was maximally increased at day 35.…”

supporting

confidence: 62%

Expression of IL-1β in supraspinal brain regions in rats with neuropathic pain

Apkarian

Lavarello

Randolf

et al. 2006

Neuroscience Letters

100

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We examined mRNA expression of the pro-inflammatory cytokine IL-1β in the brainstem, thalamus, and prefrontal cortex in two rat models of neuropathic pain. Rats received a neuropathic injury: spared nerve injury (SNI) or chronic constriction injury (CCI), sham injury, or were minimally handled (control). Neuropathic pain-like behavior was monitored by tracking tactile thresholds. SNI-injured animals showed a robust decrease in tactile thresholds of the injured foot, while CCI-injured animals did not show tactile threshold changes. Ten or 24 days after nerve injury, IL-1β gene expression in the brain was determined by RT-PCR. IL-1β expression changes were observed mainly at 10 days after injury in the SNI animals, contralateral to the injury side, with increased expression in the brainstem and prefrontal cortex. The results indicate that neuro-immune activation in neuropathic pain conditions includes supraspinal brain regions, suggesting cytokine modulation of supraspinal circuitry of pain in neuropathic conditions. KeywordsCytokines; chronic pain; brainstem; thalamus; prefrontal cortex There is now convincing evidence that cytokine expression in the peripheral nervous system and in the spinal cord play a critical role in pain behavior in various models of neuropathic injury in rodents [1][2][3]. Accumulating evidence indicates that IL-1, a major pro-inflammatory cytokine, is involved in the modulation of nociceptive information. Most of the results reported derive from the administration of this cytokine either peripherally, intrathecally or directly into the brain, for review see [4]. Whether IL-1 induces analgesia or hyperalgesia when administered centrally seems to depend on the brain region involved and on the dose injected: lower doses cause hyperalgesia and higher doses are analgesic [5;6]. On the other hand, it has been recently reported that mice in which IL-1 signaling is impaired, show reduce basal pain sensitivity [7], and attenuated neuropathic pain behaviors by reducing mechanical allodynia and thermal hyperalgesia [8].Increased levels of IL-1 have been observed in the cerebrospinal fluid of chronic pain patients [9]. Cytokine expression in pain states has rarely been studied above the spinal cord. Even

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“…Subsequent to nerve injury, microglia in the spinal cord become activated and pro-inflammatory cytokines are released, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β. In addition, the activation of glia is accompanied by the release of chemical mediators, including substance P, inflammatory cytokines and chemokines, which subsequently enhance the activation of spinal glia (3)(4)(5)(6)(7). The suppression of microglia activity is has been explored as a potential therapy for a number of central nervous system (CNS) inflammatory diseases and neuropathic pain (8).…”

Section: Introductionmentioning

confidence: 99%

Effect of pioglitazone on neuropathic pain and spinal expression of TLR-4 and cytokines

Jia

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The molecular mechanisms underlying neuropathic pain have yet to be elucidated. The present study aimed to examine the modulation of neuroimmune activation in the spinal cord by the synthetic peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, pioglitazone (Pio), in a rat model of neuropathic pain induced by chronic constriction injury (CCI). Rats were randomly assigned into four groups: Sham surgery with vehicle, chronic constriction injury with vehicle or Pio (10 mg/kg), and chronic constriction injury with Pio and a PPAR-γ antagonist GW9662 (2 mg/kg). Pio or vehicle was administered 1 h prior to the surgery and continued daily until day 7 post-surgery. Paw pressure threshold was measured prior to surgery and on days 0, 1, 3 and 7 post-surgery. Microglia activation markers macrophage antigen complex-1, the mRNA expression levels of tumor necrosis factor α and interleukin-1β, and the mRNA expression levels of toll like receptor (TLR-4) in the lumbar spinal cord were determined. Administration of Pio resulted in the prominent attenuation of mechanical hyperalgesia. In addition, Pio was able to significantly inhibit neuroimmune activation characterized by glial activation, the production of cytokines and expression levels of TLR-4. Concurrent administration of a PPAR-γ antagonist, GW9662, reversed the effects of Pio. The antihyperalgesic effect of administration of Pio in rats receiving CCI may, in part, be attributed to the inhibition of neuroimmune activation associated with the sustaining of neuropathic pain.

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Contralateral non-operated nerve to transected rat sciatic nerve shows increased expression of IL-1β, TGF-β1, TNF-α, and IL-10

Cited by 55 publications

References 39 publications

Intra- and Extraneuronal Changes of Immunofluorescence Staining for TNF- and TNFR1 in the Dorsal Root Ganglia of Rat Peripheral Neuropathic Pain Models

Intra- and Extraneuronal Changes of Immunofluorescence Staining for TNF- and TNFR1 in the Dorsal Root Ganglia of Rat Peripheral Neuropathic Pain Models

Expression of IL-1β in supraspinal brain regions in rats with neuropathic pain

Effect of pioglitazone on neuropathic pain and spinal expression of TLR-4 and cytokines

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