Upregulation of CX3CL1 mediated by NF-κB activation in dorsal root ganglion contributes to peripheral sensitization and chronic pain induced by oxaliplatin administration.

Painful peripheral neuropathy is a severe side effect in oxaliplatin therapy that compromises cancer patients' quality of life. However, its underlying pathogenic mechanisms remain largely unknown. Here, we found that intraperitoneal consecutive administration of oxaliplatin significantly increased excitability of small diameter dorsal root ganglion neurons and induced thermal hyperalgesia in rats. Furthermore, the CX3CL1 expression was significantly increased after oxaliplatin treatment, and intrathecal injection of a neutralizing antibody against CX3CL1 markedly attenuated the enhanced excitability of dorsal root ganglion neurons and thermal hyperalgesia. Importantly, the upregulated CX3CL1 is mediated by the NF-κB signaling pathway, as inhibition of NF-κB p65 activation with pyrrolidine dithiocarbamate or p65 siRNA inhibited the upregulation of CX3CL1, the enhanced excitability of dorsal root ganglion neurons, and thermal hyperalgesia induced by oxaliplatin. Further studies with chromatin immunoprecipitation found that oxaliplatin treatment increased the recruitment of NF-κB p65 to the CX3Cl1 promoter region. Our results suggest that upregulation of CX3CL1 in dorsal root ganglion mediated by NF-κB activation contributes to the peripheral sensitization and chronic pain induced by oxaliplatin administration.

Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain.

Chronic musculoskeletal pain (CMP) is a common occurrence in clinical practice and there are a variety of options for the treatment of it. However, the pharmacological therapy is still considered to be a primary treatment. The recent years have witnessed the emergence of opioid crisis, yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly. The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics. The purpose of this consensus is to present the application of nonsteroidal anti-inflammatory drugs, serotonin norepinephrine reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, muscle relaxants, ion channel drugs and topical drugs in CMP.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch.

Chronic pain lasting more than 3 mo, or even several years can lead to disability. Treating chronic pain safely and effectively is a critical challenge faced by clinicians. Because administration of analgesics through oral, intravenous or intramuscular routes is not satisfactory, research toward percutaneous delivery has gained interest. The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area. It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery, which reduces the dose frequency and side effects. If not required, then the patch can be removed from the skin immediately. The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979. From then on, the transdermal patch has been widely used to treat many diseases. To date, no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery. The pain branch of the Chinese Medical Association, after meeting and discussing with experts and based on clinical evidence, developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

Expert consensus of Chinese Association for the Study of Pain on the radiofrequency therapy technology in the Department of Pain.

On the basis of continuous improvement in recent years, radiofrequency therapy technology has been widely developed, and has become an effective method for the treatment of various intractable pain. Radiofrequency therapy is a technique that uses special equipment and puncture needles to output ultra-high frequency radio waves and accurately act on local tissues. In order to standardize the application of radiofrequency technology in the treatment of painful diseases, Chinese Association for the Study of Pain (CASP) has developed a consensus proposed by many domestic experts and scholars.

Gene expression profile changes in rat dorsal horn after sciatic nerve injury.

OBJECTIVE: This study aims to investigate gene expression changes in rat dorsal horns after sciatic nerve injury (SNI). METHODS: The GSE18803 microarray data collected from young and adult rats were downloaded from GEO. After preprocessing, differentially expressed genes (DEGs) between SNI and sham-operated groups were selected using Limma package, in young and adult group, respectively, followed by Venn analysis. Then, enrichment analyses were performed for these DEGs using DAVID. The STRING database was used to identify protein-protein interactions (PPIs) among these DEGs, and the module network was further extracted using plugin ClusterONE. Finally, protein domain enrichment analysis of DEGs in each module was performed using InterPro database. RESULTS: Totally, 210 and 50 DEGs were identified in adult and young group, respectively. Among them, 160 were specific in adult group (e.g. CCL2, NF-κB1 and RAC2); 9 were specific in young group (e.g. ILF3 and LYVE1); and 41 were common in both two groups (e.g. FCER1G, C1QA, C1QB and C1QC). The up-regulated DEGs were mostly enriched in immune response-related biological processes, as well as 15 immune- and inflammation-related pathways. Then, two modules were identified in PPI network. CCL2 and NF-κB1 had high connectivity degrees in module 1, and RAC2, FCER1G and CD68 in module 2. CONCLUSION: CCL2, NF-κB1, RAC2, FCER1G and C1Q may contribute to the generation of neuropathic pain after SNI via immune and defense pathways. Among the five genes, the first three are specific in adult population, while the latter two are age-independent. They all might function through involvement of these immune or inflammatory pathways.

The influence of thiamin on the efficacy of pregabalin in rats with spinal nerve ligation (SNL)-induced neuropathic pain.

OBJECTIVE: The thiamin is often used in the treatment of neuropathy, and pregabalin is often used to treat neuropathic pain. Our study examined the influence of thiamin on the efficacy of pregabalin in a rat model of spinal nerve ligation (SNL)-induced neuropathic pain. METHODS: Sprague-Dawley male rats were randomly divided into six groups. The neuropathic pain-relieving properties were measured by plantar test, cold plate test, and hot plate test after administration of pregabalin (i.v) and/or thiamin (i.p) in SNL rats 14 days after operation. RESULTS: In the therapy period, pregabalin, or thiamin alone all produced antinociceptive effects in rats with neuropathic pain. And combination treatment of thiamin and pregabalin resulted in an enhanced pain relief compared to the administration of pregabalin or thiamin alone. CONCLUSION: Combination of thiamin and pregabalin produces an additive antinociceptive effect in neuropathic pain rats, this drug combination may offer a beneficial treatment option for neuropathic pain.