An understudied symptom of the genetic disorder Neurofibromatosis type 1 (NF1) is chronic idiopathic pain. We used targeted editing of Nf1 in rats to provide direct evidence of a causal relationship between neurofibromin， the protein product of the Nf1 gene， and pain responses. Our study data identified a protein-interaction network with collapsin response meditator protein 2 (CRMP2) as a node and neurofibromin， syntaxin 1A， and the N-type voltage-gated calcium (CaV2.2) channel as interaction edges. Neurofibromin uncouples CRMP2 from syntaxin 1A. Upon loss/mutation of neurofibromin， as seen in patients with NF1， the CRMP2/Neurofibromin interaction is uncoupled， which frees CRMP2 to interact with both syntaxin 1A and CaV2.2， culminating in increased release of the pro-nociceptive neurotransmitter calcitonin gene-related peptide (CGRP). Our work also identified the CRMP2-derived peptide CNRP1， which uncoupled CRMP2's interactions with neurofibromin， syntaxin 1A， as well as CaV2.2. Here， we tested if CRISPR/Cas9-mediated editing of the Nf1 gene， which leads to functional remodeling of peripheral nociceptors through effects on the tetrodotoxin-sensitive (TTX-S) Na voltage-gated sodium channel (NaV1.7) and CaV2.2， could be affected using CNRP1， a peptide designed to target the CRMP2-neurofibromin interface. The data presented here shows that disrupting the CRMP2-neurofibromin interface is sufficient to reverse the dysregulations of voltage-gated ion channels and neurotransmitter release elicited by Nf1 gene editing. As a consequence of these effects， the CNRP1 peptide reversed hyperalgesia to thermal stimulation of the hindpaw observed in Nf1-edited rats. Our findings support future pharmacological targeting of the CRMP2/neurofibromin interface for NF1-related pain relief.