In vivo microdialysis of glutamate in ventroposterolateral nucleus of thalamus following electrolytic lesion of spinothalamic tract in rats

Abstract

Central pain is one of the most important complications after spinal cord injury (SCI), and thereby, its treatment raises many challenges. After SCI, in a cascade of molecular events, a marked increase in glutamate at the injury site results in secondary changes which may impact on supraspinal regions, mainly ventroposterolateral (VPL). There is little information about the changes in glutamate metabolism in the VPL and whether it contributes to SCI-related central pain. The present study was performed to evaluate glutamate release in the VPL following electrolytic lesion of spinothalamic tract (STT). A laminectomy was performed at spinal segments of T9-T10 in male rats, and then, unilateral electrolytic lesions were made in the STT. Glutamate concentrations in ipsilateral VPL dialysate were measured by HPLC method at days 3, 7, 14, 21 and 28 post-injury. Tactile pain and motor activity were also examined. Glutamate levels were significantly increased in ipsilateral VPL of spinal-cord-injured rats 2 weeks after SCI and remained high up to day 28 post-surgery. The STT lesions had no marked effect on our measures of motor activity, but there was a significant decrease in paw withdrawal threshold in the hind paws at day 14 post-SCI. These findings suggest that an increased release of glutamate in VPL plays a role in secondary pathologic changes, leading to neuronal hyperexcitation and neuropathic pain after SCI.

Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury-induced pain and thalamic hyperexcitability via supraspinal glutamate transporters

“…These results are also consistent with the increased hyperexcitability in the brain that is only evident after a painful facet joint injury (Fig. 2) since prolonged exposure to glutamate is correlated with increased neuronal hyperexcitability [59,60]. …”

Red nucleus glutamate facilitates neuropathic allodynia induced by spared nerve injury through non‐NMDA and metabotropic glutamate receptors

“…An accumulating body of evidence suggests that glutamate plays a role in the transduction of sensory input at the periphery and participates in the central sensitization that is associated with the development of pathological pain (Osikowicz et al, 2013). In animal models of pathological pain, increased glutamate release or transmission is observed in injured tissues, DRG, spinal cord, and different supraspinal regions, such as the anterior cingulate cortex (ACC), periaqueductal gray (PAG), and ventroposterolateral nucleus (VPL; Omote et al, 1998;Somers and Clemente, 2002;Wen et al, 2003;Xu et al, 2008;Inquimbert et al, 2012;Ho et al, 2013;Yan et al, 2013;Ghanbari et al, 2014;Gong et al, 2014;, and the drugs acting against glutamate release attenuate the painrelated behaviors induced in animal models (Bleakman et al, 2006;Kumar et al, 2010aKumar et al, , 2013Naderi et al, 2014). In contrast, intraplantar, intrathecal, or lateral ventricle injection of glutamate exhibits an algesic effect (Beirith et al, 1998;Shi et al, 2010;Osgood et al, 2013).…”

“…Recent studies indicate that glutamate plays an important role in the transduction of sensory input at the periphery and is critically involved in central sensitization, which is associated with chronic pain. Glutamate regulates nociceptive processes at different levels of the nervous system, including dorsal root ganglion (DRG), spinal cord, and different supraspinal regions (Omote et al, ; Somers and Clemente, ; Wen et al, ; Xu et al, ; Inquimbert et al, ; Ho et al, ; Osikowicz et al, ; Yan et al, ; Ghanbari et al, ; Gong et al, ; Li et al, ). However, the roles of glutamate and different types of glutamate receptors in the RN in the development of neuropathic pain are currently unknown.…”

Cortical Stimulation and Neuropathic Pain

“…Among the main supraspinal projections, the spinothalamic tract is the most prominent ascending nociceptive pathway in the spinal cord and projects into the ventral posterior lateral (VPL) and ventral posterior medial (VPM) nucleus involved with discriminative components of pain sensitivity and nonspeciic thalamic nucleus (centromedial, centrolateral, laterocentral and intralaminar), related to the affective component of pain GHANBARI et al, 2014).…”

“…On the basis of functional criteria, the main cortical regions involved in pain response are the motor cortex, primary (S-I) and secondary (S-II) sensory cortex (SCHNITZLER;PLONER, 2000;GUSTIN et al, 2012). However, it has been observed that patients with speciic brain lesions, particularly in the SI cortex, are still able to feel pain (BROOKS; TRACEY, 2005), and an intense activity has been seen in the SI cortex of patients with chronic neuropathic pain compared to patients with chronic non-neuropathic pain (GUSTIN et al, 2012).…”