<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Many brain areas participate to supraspinal control of nociception. In these regions, few studies have investigated the role of glial cells in supraspinal plasticity and the effect of 7‐day intrathecal nerve growth factor‐like (<jats:styled-content style="fixed-case">BB14</jats:styled-content>®, Blueprint Biotech, Milano, Italy) treatment.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In male <jats:styled-content style="fixed-case">S</jats:styled-content>prague‐<jats:styled-content style="fixed-case">D</jats:styled-content>awley rats, we evaluated by immunohistochemistry the morphological and molecular rearrangement of neuroglial network occurring in several supraspinal brain regions involved in pain processing following spared nerve injury (<jats:styled-content style="fixed-case">SNI</jats:styled-content>) of the sciatic nerve. In particular, the medial prefrontal cortex, the amygdala (<jats:styled-content style="fixed-case">A</jats:styled-content>my), the nucleus accumbens (<jats:styled-content style="fixed-case">A</jats:styled-content>cb), the thalamus and the periaqueductal gray were analysed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Despite the modifications occurring in the dorsal horn of spinal cord following <jats:styled-content style="fixed-case">SNI</jats:styled-content>, no significant changes in the <jats:styled-content style="fixed-case">I</jats:styled-content>ba1 and glial fibrillary acidic protein (<jats:styled-content style="fixed-case">GFAP</jats:styled-content>) expression were detected in all the analysed supraspinal regions, except for the <jats:styled-content style="fixed-case">A</jats:styled-content>my, showing a remarkable <jats:styled-content style="fixed-case">GFAP</jats:styled-content> increase. Interestingly, neuropathic rats also displayed a significant increase of glial transporters (<jats:styled-content style="fixed-case">GTs</jats:styled-content>) in all the supraspinal regions. Finally, the analysis of vesicular glutamate transporter 1 (<jats:styled-content style="fixed-case">vGLUT1</jats:styled-content>) and vesicular gamma‐aminobutyric acid (GABA) transporter<jats:styled-content style="fixed-case"> (vGAT)</jats:styled-content> expression revealed a significant enhancement of glutamatergic/<jats:styled-content style="fixed-case">GABA</jats:styled-content>ergic ratio in all selected brain regions of <jats:styled-content style="fixed-case">SNI</jats:styled-content> animals, except for <jats:styled-content style="fixed-case">A</jats:styled-content>cb. Both glial activation in the <jats:styled-content style="fixed-case">A</jats:styled-content>my and alteration of <jats:styled-content style="fixed-case">GTs</jats:styled-content> and <jats:styled-content style="fixed-case">vGLUT/vGAT</jats:styled-content> levels observed in neuropathic animals were largely reversed by <jats:styled-content style="fixed-case">BB14</jats:styled-content>® treatment.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>All together, these data strengthen the role of supraspinal neuroglial network plasticity in the establishment of neuropathic pain syndrome. The hallmark is represented by the divergence between glial reaction confined to <jats:styled-content style="fixed-case">A</jats:styled-content>my and the widespread changes in the <jats:styled-content style="fixed-case">GT</jats:styled-content> distribution and glutamate/<jats:styled-content style="fixed-case">GABA</jats:styled-content> ratio detected in the other supraspinal region.</jats:p></jats:sec>