Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model

Abstract

There is a growing body of evidence that cytokines contribute to both induction and maintenance of neuropathic pain derived from changes in dorsal root ganglia (DRG), including the activity of the primary sensory neurons and their satellite glial cells (SGC). We used immunofluorescence and in situ hybridization methods to provide evidence that chronic constriction injury (CCI) of the sciatic nerve induces synthesis of interleukin-6 (IL-6) in SGC, elevation of IL-6 receptor (IL-6R) and activation of signal transducer and activator of transcription 3 (STAT3) signalling. Unilateral CCI of the rat sciatic nerve induced mechanoallodynia and thermal hyperalgesia in ipsilateral hind paws, but contralateral paws exhibited only temporal changes of sensitivity. We demonstrated that IL-6 mRNA and protein, which were expressed at very low levels in naïve DRG, were bilaterally increased not only in L4-L5 DRG neurons but also in SGC activated by unilateral CCI. Besides IL-6, substantial increase of IL-6R and pSTAT3 expression occurred in SGC following CCI, however, IL-6R associated protein, gp130 levels did not change. The results may suggest that unilateral CCI of the sciatic nerve induces bilateral activation of SGC in L4-L5 DRG to transduce IL-6 signalling during neuroinflammation.

Characterization of Frequency-Dependent Responses of the Vascular System to Repetitive Vibration

“…29,[34][35][36] Compared with cage-control rats, rats in all other groups displayed an increase in MAPK-8 and decrease in STAT3 expression in the DRG. However, these changes were only significant in the restraint-control rats and rats exposed to vibration at 250 Hz.…”

An Approach to Identify Nerve Injury-Evoked Changes that Contribute to the Development or Protect Against the Development of Sustained Neuropathic Pain

“…Following nerve injury there is an invasion of immune cells into the nervous system that is promoted largely by the Wallerian degeneration of the injured nerve as well as by damage of the tissue surrounding the nerve (Chung et al, 2007;Dubovy et al, 2007;Hu and McLachlan, 2002). The immune cells alter the neuronal environment in part by changing the level of various cytokines/chemokines produced by the immune cells and by the neurons and glial cells in response to those released by the immune cells (Austin and MoalemTaylor; Brazda et al, 2009;Dubovy et al, 2006;Dubovy et al, 2010a;Dubovy et al, 2010b). Since some of the immune mediators have been shown to contribute to neuropathic pain by altering the excitability of both primary and secondary sensory neurons one approach that has been investigated to treat/prevent chronic pain is to pharmacologically alter their production.…”

Células gliales satélite de ganglios sensoriales: su papel en el dolor

“…de monocitos 1 a través del receptor, produciendo citocinas como TNF-␣ 23,67 , IL-1␤ 77 e IL-6 78 . La capacidad que tienen las CGS de sintetizar TNF-␣ en respuesta a una lesión periférica quedó demostrada en un modelo adaptado de lesión en la faceta articular de la columna lumbar de ratones 67 y en 3 modelos de dolor en el nervio ciático (vínculo parcial unilateral, vínculo del nervio espinal y transección).…”

“…De hecho, fue observado un aumento bilateral de la expresión de IL-6 en las CGS del GRD, como también de su receptor en el ganglio ipsilateral, posteriormente a la lesión del nervio ciático por constricción crónica 78 . En resumen, las citocinas participan en la interacción entre la neurona y la CGS, existiendo cada vez más evidencias acerca de un posible papel de las citocinas con origen en los ganglios sensoriales en la inducción y en el mantenimiento del dolor neuropático 83 .…”