Overexpression Of GPR7 In Schwann Cells From Patients With Peripheral Neuropathies

The identification of regulated gene products that play a role in Schwann cell-axon contact after nerve injuries may have important implications for pain mechanisms and nerve repair processes. Schwann cell-intrinsic defects have been recently shown to cause neuropathies associated with pain (Gillespie et al., 2000). The 7TM GPR7, originally described by O'Dowd et al. (1995) as a likely G-protein coupled receptor, is a human orphan receptor expressed in the nervous system with sequence similarity to both somatostatin and opioid receptors. Using real time quantitative PCR^TM we evaluated the expression of GPR7 in sural nerve biopsies from patients with different kinds of peripheral neuropathies. We observed that GPR7 expression was significantly (p < 0.001) increased in sural nerves when an epineurial and endoneurial perivascular inflammatory infiltration was present. The overexpression was particularly noted in patients with painful peripheral neuropathies with an inflammatory, immuno and vasculitic etiology. In order to confirm changes in GPR7 expression at the protein level, we performed immunofluorescence staining on sections of neuropathic human sural nerves. A comparative analysis of rat injured sciatic nerves was also performed. We observed that GPR7 receptor is expressed by Schwann cells and that the amount of Schwann cell-staining in both human and rat nerve is increased in conditions of inflammatory neuropathy. In addition, we observed that the expression of GPR7 was significantly decreased in severe axonal neuropathies, suggesting that GPR7 expression is axon dependent. Immunofluorescence staining in rat cultured Schwann cells suggested that the expression GPR7 increased during Schwann-axon interaction. Taken together these results suggest that molecules such as GPR7 whose expression in Schwann cells varies under pathological conditions may play a role in the pathogenesis of human neuropathies. Altered GPR7 expression may disrupt myelination leading to progression of the neuropathy. Alternatively, GPR7 may play a role in Schwann cell-axon signaling and thereby influence axonal function in neuropathies leading to a painful phenotype.