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

Abstract

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

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

“…This indicated that the algogenic effect of microgliaderived MVs was mediated, at least partly, by IL-1β. This is in agreement with previous reports that IL-1β acts as a mediator of supraspinal circuits of pain in neuropathic conditions [46][47][48].…”

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

“…The anterior half-brain tissue (including mainly prefrontal cortex, weighing 150-200 mg), excluding the olfactory bulbs, which were contralateral to the operation side, was dissected 17 and homogenized in a buffer consisting of a protease inhibitor (Roche Diagnostics, Mannheim, Germany) using Power Gen 124 tissue tearer (Fisher Scientific Co., Suwanee, GA, USA). Samples were spun at 20,000g for 30 min at 4°C.…”

Minocycline modulates neuropathic pain behaviour and cortical M1–M2 microglial gene expression in a rat model of depression

“…Pre-clinical studies have demonstrated peripheral nerve injury-induced neuroimmune activation in brain regions responsible for the modulation of nociception and/or affect, including the prefrontal cortex (Apkarian et al, 2006, Al-Amin et al, 2011. Furthermore, the expression of genes coding for the pro-inflammatory cytokines IL-1β, IL-6 and/or TNFα, is enhanced in brain regions responsible for processing emotion and pain in animal models of depression with concomitant inflammatory (Kim et al, 2012, Arora et al, 2011 and neuropathic (Norman et al, 2010, Apkarian et al, 2006, Burke et al, 2013a, Burke et al, 2013b pain-related responding. Thus, modulating neuroimmune responses has been proposed as a novel target for the treatment of CNS disorders with an inflammatory component, including depression and associated chronic pain.…”

“…The prefrontal cortex was chosen as it is a key brain region implicated in the interaction between depression and pain. Depressed patients exhibit increased activation of the prefrontal cortex in response to pain (Graff-Guerrero et al, 2008, Lopez-Sola et al, 2010, Bar et al, 2007, inhibition of prefrontal cortical activity enhances inflammatory hyperalgesia in the chronic mild stress rat model of depression (Qi et al, 2013), and the prefrontal cortex has been shown to exhibit altered neuroimmune activation/functioning in the OB model (Borre et al, 2012, Myint et al, 2007 and following nerve injury (Apkarian et al, 2006).…”