The role of PTEN in primary sensory neurons in processing itch and thermal information in mice.

PTEN is known as a tumor suppressor and plays essential roles in brain development. Here, we report that PTEN in primary sensory neurons is involved in processing itch and thermal information in adult mice. Deletion of PTEN in the dorsal root ganglia (DRG) is achieved in adult Drg11 -Cre^ER: PTEN ^flox/flox (PTEN CKO) mice with oral administration of tamoxifen, and CKO mice develop pathological itch and elevated itch responses on exposure to various pruritogens. PTEN deletion leads to ectopic expression of TRPV1 and MrgprA3 in IB4⁺ non-peptidergic DRG neurons, and the TRPV1 is responsive to capsaicin. Importantly, the elevated itch responses are no longer present in Drg11 -Cre^ER: PTEN ^flox/flox: TRPV1 ^flox/flox (PTEN : TRPV1 dCKO) mice. In addition, thermal stimulation is enhanced in PTEN CKO mice but blunted in dCKO mice. PTEN-involved regulation of itch-related gene expression in DRG neurons provides insights for understanding molecular mechanism of itch and thermal sensation at the spinal level. [Display omitted] • PTEN is mainly expressed in IB4⁺ non-peptidergic dorsal root ganglion (DRG) neurons • Adult deletion of PTEN in DRG leads to augmented itch and enhanced thermal nociception • TRPV1⁺ neurons are significantly increased in the DRG of PTEN CKO mice • Ectopic TRPV1 expression in DRG neurons causes itch and thermal responses in PTEN CKO Hu et al. report that PTEN, a tumor-suppressor gene, is involved in processing itch and thermal information in adult mice. They reveal that PTEN also suppresses expression of itch-related genes in primary sensory neurons and when defective leads to elevated itch and thermal sensation at the spinal level. [ABSTRACT FROM AUTHOR]