Characterizing the opioidergic mechanisms of repetitive transcranial magnetic stimulation-induced analgesia: a randomized controlled trial.

ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of ß-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids.

Identification of Candidate Genes Associated with Postherpetic Neuralgia Susceptibility.

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most common complications of herpes zoster (HZ). Heritable factors have been found to play a role in various clinical pain symptoms. However, the effect of gene variability on the susceptibility of PHN remains poorly understood. OBJECTIVES: The aim of this study was to evaluate whether genetic variation in pain pathway genes was associated with PHN susceptibility in the Chinese population. STUDY DESIGN: Case-control study. SETTING: Department of Anesthesiology and Pain Medicine in a university hospital. METHODS: Seventy patients with PHN and 111 patients with HZ without developing PHN were enrolled. All patients received standardized antiviral agents and analgesics as needed during the acute phase of HZ. Twenty-four candidate genetic polymorphisms in 12 genes (IL1B, SCN9A, KCNK9, TRPV1, P2RX7, HTR1A, HTR2A, ADRB1, ADRB2, BDNF, COMT, and OPRM1) were genotyped in all patients. Multivariable logistic regression analyses were used to identify genetic variations associated with PHN susceptibility while controlling for potential confounders. RESULTS: Our results suggested that only variation in P2RX7 gene was associated with PHN susceptibility. The P2RX7 rs7958311 AG heterozygous genotype carriers had a decreased risk for PHN in the overdominant model (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.21-0.77; P = 0.005), and codominant model (OR, 0.44; 95% CI, 0.20-0.98; P = 0.045). The P2RX7 rs7958311 GG homozygote genotype was associated with an increased risk for PHN under a recessive model (OR, 2.15; 95% CI, 1.01-4.56; P = 0.046). There were no significant associations between the other 23 single-nucleotide polymorphisms and PHN susceptibility. LIMITATIONS: Lack of validation cohort to verify the findings. CONCLUSIONS: In the present study in the Chinese population, we found purinergic receptor P2X7 rs7958311 may contribute to PHN development after HZ. Future larger independent cohorts are warranted to replicate these initial findings. KEY WORDS: Herpes zoster, postherpetic neuralgia, polymorphisms.

Computed Tomography (CT)-Guided Percutaneous Thoracic Sympathetic Chain Radiofrequency Thermocoagulation for Raynaud Disease.

BACKGROUND We introduce a minimally invasive technique for the treatment of Raynaud disease - CT-guided percutaneous thoracic sympathetic chain radiofrequency thermocoagulation. MATERIAL AND METHODS Under CT guidance, the radiofrequency needle was punctured from the upper edge of the costotransverse joint to the anterior superior edge of the 4th capitulum costae and the lateral parietal pleura. After sensorial (1.5 mA, 50 Hz) and motorial (1.5 mA, 2Hz) testing to determine that there was no nerve innervation zone with muscle numbness and twitches, radiofrequency coagulation was set at 95°C for 300 s. RESULTS A total of 17 patients were enrolled in the treatment group. All the patients underwent CT-guided percutaneous thoracic sympathetic chain puncture of the needles to the upper edge of the 4th capitulum costae on both sides. The perfusion index (PI) of the fingers began to rise 30 s after radiofrequency thermocoagulation, and the palm temperature (T) began to rise after 90 s. At the end of treatment, PI increased by an average of 4.6-fold, and the T average rose by 3.6°C. Postoperative cold-water stimulation testing could no longer induce Raynaud disease. Follow-up was conducted for 1 to 15 months. Two patients were found to have recurrence at 9 months and 13 months, respectively. CONCLUSIONS CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency coagulation can effectively treat Raynaud disease.