Nerve growth factor (
NGF), an essential
peptide for sensory neurons, seems to have opposite effects when administered peripherally or directly to the central nervous system. We investigated the effects of 7-days intrathecal (i.t.) infusion of
NGF on neuronal and glial spinal markers relevant to neuropathic behavior induced by chronic constriction injury (CCI) of the sciatic nerve. Allodynic and hyperalgesic behaviors were investigated by Von Frey and thermal Plantar tests, respectively.
NGF-treated animals showed reduced
allodynia and
thermal hyperalgesia, compared to control animals. We evaluated on lumbar spinal cord the expression of microglial (ED-1), astrocytic (GFAP and
S-100beta), and C- and Adelta-fibers (
SubP, IB-4 and Cb) markers. I.t.
NGF treatment reduced reactive
astrocytosis and the density of
SubP, IB4 and Cb positive fibers in the dorsal horn of injured animals. Morphometric parameters of proximal sciatic nerve stump fibers and cells in DRG were also analyzed in CCI rats: myelin thickness was reduced and DRG neurons and satellite cells appeared hypertrophic. I.t.
NGF treatment showed a beneficial effect in reversing these molecular and morphological alterations. Finally, we analyzed by immunohistochemistry the expression pattern of
neurotrophin receptors TrkA, pTrkA, TrkB and p75(NTR). Substantial alterations in
neurotrophin receptors expression were observed in the spinal cord of CCI and
NGF-treated animals. Our results indicate that i.t.
NGF administration reverses the neuro-glial morphomolecular changes occurring in neuropathic animals paralleled by alterations in
neurotrophin receptors ratio, and suggest that
NGF is effective in restoring homeostatic conditions in the spinal cord and maintaining
analgesia in
neuropathic pain.