Apoptotic genes expression in the lumbar dorsal horn in a model neuropathic pain in rat

Abstract

This study combines behavioural, molecular and morphological approaches to assess the occurrence of apoptosis in the rat spinal cord by 14-day sciatic nerve chronic constrictive injury (CCI). Thermal allodynia developed in the corresponding footpad 2-3 days after surgery, while morphological features, evaluated 14 days later, consisted in a decrease (23 +/- 7%) in laminae I-III cell number ipsilateral to CCI. Apoptosis occurrence was possibly suggested by the presence of some TUNEL-positive nuclei in this territory. The mRNA expression levels of the bcl-2 genes family was changed as follows: bax increased up to 40% in CCI vs the sham rats, while bcl-2 did not change; bcl-xS massively decreased (by 70% and 100%), while bcl-xL increased (by 40%) in CCI rats. Western blot analysis showed no change either on poly-ADP ribose polymerase (PARP) or p53 transcription factor in CCI and sham rats. These data suggest that in a chronic pain condition, where the acute phase has already resolved, specific apoptotic genes are still operative and possibly may serve as a critical change for cells surviving in the chronic pain state.

Attenuation of oxidative stress, inflammation and apoptosis by ethanolic and aqueous extracts of Crocus sativus L. stigma after chronic constriction injury of rats

“…The balance between Bax, a pro-apoptotic protein, and Bcl-2, an antiapoptotic protein, stabilizing membrane permeability is very important in apoptosis induction (Oltvai et al 1993). Our western blot data showed that Bax/Bcl-2 ratio was elevated following CCI, supporting evidence that in the CCI of sciatic nerve, the development of neuropathic pain may be associated with the activation of apoptosis (Siniscalco et al 2007, Maione et al 2002. Bax/Bcl2 ratio declined in the spinal cord of rats treated with saffron's extracts on day 3.…”

“…Scientific studies have verified many traditional uses of such expensive spice. Saffron Pain initiated or caused by a primary lesion or dysfunction in the nervous system is defined as being a neuropathic pain and triggers a cascade of events in the central or peripheral nervous system, including excitotoxicity, oxidative stress, inflammatory process and apoptotic like cell death mechanisms (Maione et al 2002). In our previous work, antiallodynic and antihyperalgesic effects of ethanolic and aqueous extracts of saffron were shown in rats that underwent chronic constriction injury (CCI) of the sciatic nerve .…”

Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions

“…The measured mRNA levels were normalized with three housekeeping genes: hypoxanthine-guanine phosphoribosyltransferase (HPRT), 18S ribosomal RNA (18S), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The HPRT, 18S, and GAPDH housekeeping genes were chosen because their gene expression did not change in different experimental conditions including SNI-induced neuropathic pain (Bangaru et al 2012;Maione et al 2002;Piller et al 2013;Siniscalco et al 2007Siniscalco et al , 2010. The gene expression values are expressed as arbitrary units Ϯ SE.…”

Loss of Neurons from Laminas I-III of the Spinal Dorsal Horn Is Not Required for Development of Tactile Allodynia in the Spared Nerve Injury Model of Neuropathic Pain

“…de Novellis et al (2004) reported an apparent reduction of ϳ50% in the number of neurons in lamina II on both sides of the spinal cord 7 d after CCI. However, these authors previously detected a reduction of only 23% of neurons in laminas I-III on the ipsilateral side 14 d after CCI (Maione et al, 2002). It is hard to reconcile these two findings, and because they were both obtained from simple profile counts, rather than with a stereological method (see below), they must be treated with considerable caution.…”