Click to download
Thalamic C-FOS expression in a rat monoarthritic model The thalamus is an integral relay structure for the supraspinal receipt, integration and onward transfer of nociceptive information within the central nervous system. It predominantly receives ascending nociceptive input via second order neurons that originate in lamina I of the spinal cord dorsal horn and terminate at anatomically distinct regions within the thalamus. The inflammatory process causes activation of both central and peripheral pain signalling pathways; this is manifest in multiple symptoms including hyperalgesia, allodynia and ongoing pain. c-Fos is an immediate early gene that is rapidly expressed within neurons in response to stimulation, causing the production of the nuclear protein fos, an important nuclear protein involved in the upregulation of downstream target genes and is commonly employed as a marker of neuronal activation (Bullitt, 1990). The aim of this study was to assess fos expression within specific thalamic nuclei both ipsi- and contralaterally in the monoarthritic rat model. Complete Freund’s adjuvant (CFA) containing Mycobacterium tuberculosis was administered into the dorsal surface of the right hind paw of male Sprague Dawley rats (230-250g), resulting in both acute (day 1-2) and chronic (day 14 onwards) phases of pain (Devall et al., 2005). Weight bearing differences between the affected and unaffected paws and paw volume changes were used to assess the progression of the inflammatory response at early (day 1) and late (day 15) time points. Control groups receiving no injection, incomplete Freund’s adjuvant (IFA), or phosphate buffered saline (PBS) were also included (n=3 for each group at each time point). Fos expression was determined using immunohistochemistry following tissue fixation with paraformaldehyde (PFA) in freely floating sections (50 μm) taken between -2.56 and -3.6mm anterior-posterior with respect to bregma. The sections were subject to image analysis to obtain a relative optical density (ROD) for fos staining of specific thalamic nuclei: ventral posterolateral (VPL), ventral posteromedial (VPM), reticular (Rt), posterior ( Po), ventrolateral (VL) and ventromedial (VM). Our findings showed a significant increase in fos expression (P<0.05, one-sided t-test) in the early phase comparing the CFA with IFA (all nuclei) and PBS groups (all nuclei except VL) contralateral to the insult. The largest change in ROD was seen in the contralateral Po (188.63 ± 17.63; % ± SEM) in comparison to IFA group. Significant increases (P<0.05) were also observed ipsilateral to the insult in the Po and VM in comparison to IFA group. These findings reflect the immediate, transient nature of c-Fos expression with increased expression in response to the acute pain phase. In the late phase, a significant difference (P<0.05) was only observed between the CFA and PBS groups in the Rt region contralateral to the insult. This indicates that c-Fos activation in the thalamus is not associated with the chronic pain phase in this model. It may be hypothesised that changes occur downstream of c-Fos activation in intracellular mechanisms in thalamic nuclei and possibly also via projections to other supraspinal sites, which maintain the late phase response.
Bullitt, E., J. Comp. Neurol., 296 (1990) 517-530. |
