Increased Nav1.7 expression in the dorsal root ganglion contributes to pain hypersensitivity after plantar incision in rats.

Postoperative pain remains a complex problem that is difficult to manage in the clinical context, seriously affecting rehabilitation and the quality of life of patients after surgery. Nociceptors, of which the cell bodies are located in the dorsal root ganglion, are crucial for initiating and conducting the pain signal. The peripheral voltage-gated sodium channels, including Nav1.7, which is mainly expressed in the dorsal root ganglion, are key to understanding the mechanism underlying postoperative pain. Nav1.7, in particular, of which mutations in the encoding gene ( SCN9A) can determine whether pain occurs, has aroused most attention. Previous studies have shown that Nav1.7 in dorsal root ganglion is critical for the development of inflammatory pain and some neuropathic pain. However, the expression of Nav1.7 in the dorsal root ganglion after surgery and its role in postoperative pain hypersensitivity remain unclear. Therefore, in this study, in order to gain a better understanding of the role of dorsal root ganglion Nav1.7 in pain hypersensitivity following operation, we dynamically examined the pain-related behavior and expression of Nav1.7 in L4-L6 dorsal root ganglion before and after plantar incision in rats (an acute postoperative pain model). After plantar incision, the mechanical and thermal pain threshold decreased significantly, the cumulative pain score was increased significantly, meanwhile quantitative polymerase chain reaction and Western blotting results showed that expression of Nav1.7 in L4-L6 dorsal root ganglion was enhanced significantly. After pretreatment using SCN9A-RNAi-LV delivered via an intrathecal tube, immunohistochemistry showed that increased expression of Nav1.7 in L4-L6 dorsal root ganglion after plantar incision was inhibited, as also confirmed by quantitative polymerase chain reaction and Western blotting. Moreover, pain hypersensitivity was alleviated. These results suggested that Nav1.7 of L4-L6 dorsal root ganglion plays an important role in the development of pain hypersensitivity after plantar incision.

Heterogeneity of clinical features and mutation analysis of NTRK1 in Han Chinese patients with congenital insensitivity to pain with anhidrosis.

PURPOSE: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder whose core clinical features consist of no response to noxious stimuli and inability to sweat under any conditions. Our goal was to characterize the details of phenotypic and genotypic features in Chinese CIPA patients. PATIENTS AND METHODS: Personal data and clinical information were investigated by interview and physical examination. DNA was extracted from blood samples of patients and their available familial members and subjected to genetic analysis. RESULTS: A total of 41 Han Chinese CIPA patients from 35 unrelated families were recruited. The distribution of patients was mainly in the central and southern regions of China, with a male to female ratio of 3:1 and a mortality rate of 7.3%. Heterogeneity of clinical features, including pain insensitivity, temperature sensation, and complications, were cataloged. Interestingly, some patients had "visceral pain" sensation, and there was a significant difference in temperature perception and thermal pain between individuals. The incidence of bone and joint fractures was 49%. The characteristics of 19 mutations of NTRK1 in 41 patients, with five novel mutations, were identified. More than 63% of patients had the splice mutation, c.851-33 T>A, which strongly suggests that it may be a common pathogenic site in Han Chinese patients. CONCLUSION: Current findings expand our knowledge about the spectrum of phenotypic features and the racial characteristics of NTRK1 mutations of CIPA patients in the Han Chinese population.

Phenotypic and genotypic features of a pair of Chinese identical twins with congenital insensitivity to pain and anhidrosis: A case report.

RATIONALE: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disorder characterized by insensitivity to noxious stimulus and the absence of sweating. Fractures and joint destruction are common complications, but detailed studies on mineral and skeletal homeostasis are not available. Mental retardation is often reported, but detailed observations during childhood are lacking. PATIENT CONCERNS: A pair of 46-month-old Chinese identical twin brothers was presented at our hospital. The brothers had the typical manifestations of insensitivity to noxious stimulus, inability to sweat, and recurrent episodes of unexplained fever. Fortunately, they did not present common complications such as self-mutilation, trauma, bruise, and repeated bone fractures. DIAGNOSES: Two novel compound heterozygous variants of NTRK1 (c.632T > A and c.1253_1254delTC) were identified. INTERVENTIONS: The patients were subjected to routine and specialist clinical examinations. Daily care and symptomatic treatment were given. OUTCOME: X-ray films of proband 2 showed a fracture in the first metatarsal. Decreased bone mineral density (BMD) and mild-to-moderate retardation of the Gesell developmental schedules (GDS), especially language and adaptability, were observed. Evaluation results for BMD and GDS in proband 2 were worse than those in his brother. LESSONS: The current findings expand our knowledge about the spectrum of phenotypic and genotypic features of CIPA, which will help facilitate future genotype-phenotype association studies. Daily care by parents promotes favorable outcomes in patients.

Associations between single-nucleotide polymorphisms in the NTRK1 gene and basal pain sensitivity in young Han Chinese women.

OBJECTIVES: The NTRK1 gene plays an important role in sensory and sympathetic neuronal survival. Mutations in this gene cause a rare hereditary disease known as congenital insensitivity to pain with anhidrosis. The aim of this study was to explore possible associations between single-nucleotide polymorphisms (SNPs) in NTRK1 and pain perception in a selected population. METHODS: A total of 309 healthy Han Chinese female undergraduates were recruited. Responses to quantitative sensory testing of pressure pain (dull, sharp, and acupuncture) were assessed, and genotyping of 13 tag-SNPs of NTRK1 was performed in the undergraduates recruited. Association analyses were performed via logistic regression analysis after adjusting for covariates such as age and body mass index. Promising associations were replicated in 197 patients scheduled to undergo gynecological surgery. RESULTS: The results showed that nine tag-SNPs of NTRK1 were significantly associated with pressure pain thresholds (P<0.05), leading to either hypersensitivity or hyposensitivity. More specifically, four tag-SNPs, rs1800880, rs6334, rs2644604 and rs943552, revealed a highly significant (P=0.008, 0.02, 0.01, 0.01, respectively) association with lower mechanical pain sensitivity of sharp pressure pain. Individuals who carried the haplotype CTCC were hyposensitive to sharp pressure pain compared with other haplotypes. CONCLUSION: These results suggest that polymorphisms in NTRK1 play an important role in pain sensitivity in young Han Chinese women.