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

Abstract

We examined mRNA expression of the pro-inflammatory cytokine IL-1beta 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-1beta gene expression in the brain was determined by RT-PCR. IL-1beta 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.

Figure 1

Tactile thresholds (50% thresholds in grams) after peripheral nerve injury. Top panel: CCI-injury does not result in an observable difference in tactile threshold between CCI-injured foot (left ft, CCI) and contralateral uninjured foot (right ft, CCI), or in contrast to sham-injured foot (left ft, CCI-sham). B. In SNI-injury, there is a statistically highly significant decrease in tactile threshold starting with 4-days post-injury, when SNI-injured foot (left ft, SNI) threshold is compared to contralateral uninjured foot (right ft, SNI), or to sham-injured foot (left ft, SNI-sham) (p < 0.05 at 4 days, and becomes p < 0.0001 at later test days).

Figure 2

Expression of IL-1β mRNA in various brain regions at two times from neuropathic injury (fold change relative to GAPDH): A. is at 10 days post-injury, and B. at 24 days post-injury. Results for 5 groups of animals are shown for 5 brain areas. Mean and standard error is plotted, and statistically significant differences as compared to either control, or corresponding sham, are indicated (*) († = only the combination of both CCI and SNI results in significant decrease in expression from sham + control).